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Khazali AS, Hadrawi WH, Ibrahim F, Othman S, Nor Rashid N. Thrombocytopenia in dengue infection: mechanisms and a potential application. Expert Rev Mol Med 2024; 26:e26. [PMID: 39397710 PMCID: PMC11488332 DOI: 10.1017/erm.2024.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 03/18/2024] [Accepted: 05/30/2024] [Indexed: 10/15/2024]
Abstract
Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.
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Affiliation(s)
- Ahmad Suhail Khazali
- Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM) Cawangan Perlis, Arau, Perlis, Malaysia
| | - Waqiyuddin Hilmi Hadrawi
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Fatimah Ibrahim
- Department of Biomedical Engineering, Faculty of Engineering, Universiti Malaya, Kuala Lumpur, Malaysia
- Center for Innovation in Medical Engineering (CIME), Faculty of Engineering, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Shatrah Othman
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Nurshamimi Nor Rashid
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
- Center for Innovation in Medical Engineering (CIME), Faculty of Engineering, Universiti Malaya, Kuala Lumpur, Malaysia
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2
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Hashim Harka M, Siraj Z, Dibaba B, Zerihun Mamo T, Ajema B, Tsegaye A, Wordofa M. Establishing reference intervals for common hematology test parameters from apparently healthy geriatrics in Asella town, Southeast Ethiopia, 2020: a community-based cross-sectional study. Front Med (Lausanne) 2024; 11:1373283. [PMID: 38818389 PMCID: PMC11137186 DOI: 10.3389/fmed.2024.1373283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 04/29/2024] [Indexed: 06/01/2024] Open
Abstract
Background Reference intervals are an important method tool for identifying abnormal laboratory test results. Complete blood count reference values are useful to interpret complete blood count (CBC) results and make clinical decisions, but these values have not been established for geriatrics in Asella town. Therefore, this study aimed to establish reference intervals (RIs) for complete blood count (CBC) parameters from geriatric participants/subjects in Asella town, Southeast Ethiopia. Methods A community-based cross-sectional study was conducted from December 2019 to May 2020. An interviewer-administered questionnaire was used to collect data on sociodemography and other characteristics from 342 eligible geriatric participants. Weight, height, and vital signs were measured, and 8 mL of blood sample was collected. Screening tests such as HIV, HBsAg, HCV, syphilis, stool examination, and urinalysis were performed. The hematological parameter was measured using a Sysmex kx-21 hematology analyzer. The data were analyzed using SPSS version 21 software. The non-parametric independent Kruskal-Wallis test and Wilcoxon rank-sum test (Mann-Whitney U test) were used to compare the parameters between age groups and genders. The 97.5 and 2.5th percentile were the upper and lower reference limit for the population. Results According to the study's findings, the reference intervals of red blood cell, white blood cell, platelet count, hemoglobin (HGB), and hematocrit (HCT) in male geriatrics were 3.8-5.85 × 1012/L, 3.1-9.66 × 109/L, 115.8-353 × 109/L, 12.4-17.76 g/dL, and 35.06-50.2%, respectively. The respective values for women were 3.94-5.48 × 1012/L, 3.13-8.4 × 109/L, 137.5-406 × 109/L, 12.5-16.4 g/dL, and 36.09-48.2%. Most of the hematological parameters showed significant differences between the two genders (p value <0.05). Conclusion Accurate gender and age-specific reference intervals are crucial in managing patient health. The current study offers essential CBC hematological parameters that can assist clinicians in interpreting laboratory results and can improve healthcare quality in the geriatric population. Therefore, it is more relevant to use the current RIs in the geriatric set-up.
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Affiliation(s)
- Mohammed Hashim Harka
- Department of Medical Laboratory Science, College of Health Science, Arsi University, Asella, Ethiopia
| | - Zuber Siraj
- Department of Medical Laboratory Science, College of Health Science, Arsi University, Asella, Ethiopia
| | - Berhanu Dibaba
- Department of Medical Laboratory Science, College of Health Science, Arsi University, Asella, Ethiopia
| | - Tewodros Zerihun Mamo
- Department of Medical Laboratory Science, College of Health Science, Arsi University, Asella, Ethiopia
| | - Bayyisa Ajema
- Referral Hospital Clinical Laboratory Service, Dilla University, Dilla, Ethiopia
| | - Aster Tsegaye
- College of Health Science, School of Medical Laboratory Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Moges Wordofa
- College of Health Science, School of Medical Laboratory Science, Addis Ababa University, Addis Ababa, Ethiopia
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3
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Tang X, Liao R, Zhou L, Yi T, Ran M, Luo J, Huang F, Wu A, Mei Q, Wang L, Huang X, Wu J. Genistin: A Novel Estrogen Analogue Targeting ERβ to Alleviate Thrombocytopenia. Int J Biol Sci 2024; 20:2236-2260. [PMID: 38617546 PMCID: PMC11008259 DOI: 10.7150/ijbs.90483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 02/14/2024] [Indexed: 04/16/2024] Open
Abstract
Thrombocytopenia, a prevalent hematologic challenge, correlates directly with the mortality of numerous ailments. Current therapeutic avenues for thrombocytopenia are not without limitations. Here, we identify genistin, an estrogen analogue, as a promising candidate for thrombocytopenia intervention, discovered through AI-driven compound library screening. While estrogen's involvement in diverse biological processes is recognized, its role in thrombopoiesis remains underexplored. Our findings elucidate genistin's ability to enhance megakaryocyte differentiation, thereby augmenting platelet formation and production. In vivo assessments further underscore genistin's remedial potential against radiation-induced thrombocytopenia. Mechanistically, genistin's efficacy is attributed to its direct interaction with estrogen receptor β (ERβ), with subsequent activation of both ERK1/2 and the Akt signaling pathways membrane ERβ. Collectively, our study positions genistin as a prospective therapeutic strategy for thrombocytopenia, shedding light on novel interplays between platelet production and ERβ.
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Affiliation(s)
- Xiaoqin Tang
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
- School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China
| | - Rui Liao
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
- School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China
| | - Ling Zhou
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
- School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China
| | - Taian Yi
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Mei Ran
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
| | - Jiesi Luo
- School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China
| | - Feihong Huang
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
| | - Anguo Wu
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
| | - Qibing Mei
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
| | - Long Wang
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
| | - Xinwu Huang
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
| | - Jianming Wu
- Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China
- School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China
- Education Ministry Key Laboratory of Medical Electrophysiology, Southwest Medical University, Luzhou 646000, China
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4
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Christakoudi S, Tsilidis KK, Evangelou E, Riboli E. Interactions of platelets with obesity in relation to lung cancer risk in the UK Biobank cohort. Respir Res 2023; 24:249. [PMID: 37848891 PMCID: PMC10580651 DOI: 10.1186/s12931-023-02561-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 10/10/2023] [Indexed: 10/19/2023] Open
Abstract
BACKGROUND Platelet count (PLT) is associated positively with lung cancer risk but has a more complex association with body mass index (BMI), positive only in women (mainly never smokers) and inverse in men (mainly ever smokers), raising the question whether platelets interact with obesity in relation to lung cancer risk. Prospective associations of platelet size (an index of platelet maturity and activity) with lung cancer risk are unclear. METHODS We examined the associations of PLT, mean platelet volume (MPV), and platelet distribution width (PDW) (each individually, per one standard deviation increase) with lung cancer risk in UK Biobank men and women using multivariable Cox proportional hazards models adjusted for BMI and covariates. We calculated Relative Excess Risk from Interaction (RERI) with obese (BMI ≥ 30 kg/m2), dichotomising platelet parameters at ≥ median (sex-specific), and multiplicative interactions with BMI (continuous scale). We examined heterogeneity according to smoking status (never, former, current smoker) and antiaggregant/anticoagulant use (no/yes). RESULTS During a mean follow-up of 10.4 years, 1620 lung cancers were ascertained in 192,355 men and 1495 lung cancers in 218,761 women. PLT was associated positively with lung cancer risk in men (hazard ratio HR = 1.14; 95% confidence interval (CI): 1.09-1.20) and women (HR = 1.09; 95%CI: 1.03-1.15) but interacted inversely with BMI only in men (RERI = - 0.53; 95%CI: - 0.80 to - 0.26 for high-PLT-obese; HR = 0.92; 95%CI = 0.88-0.96 for PLT*BMI). Only in men, MPV was associated inversely with lung cancer risk (HR = 0.95; 95%CI: 0.90-0.99) and interacted positively with BMI (RERI = 0.27; 95%CI = 0.09-0.45 for high-MPV-obese; HR = 1.08; 95%CI = 1.04-1.13 for MPV*BMI), while PDW was associated positively (HR = 1.05; 95%CI: 1.00-1.10), with no evidence for interactions. The associations with PLT were consistent by smoking status, but MPV was associated inversely only in current smokers and PDW positively only in never/former smokers. The interactions with BMI were retained for at least eight years of follow-up and were consistent by smoking status but were attenuated in antiaggregant/anticoagulant users. CONCLUSIONS In men, PLT was associated positively and MPV inversely with lung cancer risk and these associations appeared hindered by obesity. In women, only PLT was associated positively, with little evidence for interaction with obesity.
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Affiliation(s)
- Sofia Christakoudi
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK.
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK.
| | - Konstantinos K Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Evangelos Evangelou
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK
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Xu P, Han S, Hou M, Zhao Y, Xu M. The serum lipid profiles in immune thrombocytopenia: Mendelian randomization analysis and a retrospective study. Thromb J 2023; 21:107. [PMID: 37833799 PMCID: PMC10571271 DOI: 10.1186/s12959-023-00551-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by increased platelet destruction and impaired thrombopoiesis. The changes in platelet indices depend on the morphology and volume of platelets. Serum lipids have been found to affect platelet formation and activity in certain diseases, thus inducing the corresponding variation of platelet indices. METHODS Mendelian randomization (MR) analysis was performed based on databases. The clinical data from 457 ITP patients were retrospectively collected and analyzed, including platelet indices, serum lipids, hemorrhages and therapeutic responses. RESULTS MR analysis showed low high-density-lipoprotein-cholesterol (HDL-C), low apolipoprotein A-1, high triglyceride (TG) and high apolipoprotein B (ApoB) caused high platelet distribution width (PDW); high low-density-lipoprotein-cholesterol (LDL-C) increased mean platelet volume (MPV). In ITP, there were positive correlations between platelet count with TG, PDW with HDL-C and ApoB, and plateletcrit with TG and non-esterified fatty acid, and the correlation had gender differences. Bleeding scores were negatively correlated with cholesterol and LDL-C. LDL-C and homocysteine were risk factors for therapeutic responses. CONCLUSIONS Serum lipids, especially cholesterol were tightly correlated with platelet indices, hemorrhage and therapeutic effects in ITP patients. These results provide clinical references for the management of serum lipids, and highlight the necessity to further explore the relationship between lipids and pathogenesis of ITP. TRIAL REGISTRATION No: NCT05095896, October 14, 2021, retrospectively registered.
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Affiliation(s)
- Pengcheng Xu
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, China
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
| | - Shouqing Han
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, China
- Shandong Provincial Key Laboratory of Immunohematology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Shanghai, China
| | - Ming Hou
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, China
- Shandong Provincial Key Laboratory of Immunohematology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Shanghai, China
- Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Jinan, China
| | - Yajing Zhao
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, China.
- Shandong Provincial Key Laboratory of Immunohematology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Shanghai, China.
| | - Miao Xu
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, China.
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Huang L, Xu J, Zhang H, Wang M, Zhang Y, Lin Q. Application and investigation of thrombopoiesis-stimulating agents in the treatment of thrombocytopenia. Ther Adv Hematol 2023; 14:20406207231152746. [PMID: 36865986 PMCID: PMC9972067 DOI: 10.1177/20406207231152746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 01/06/2023] [Indexed: 03/02/2023] Open
Abstract
Platelets, derived from a certain subpopulation of megakaryocytes, are closely related to hemostasis, coagulation, metastasis, inflammation, and cancer progression. Thrombopoiesis is a dynamic process regulated by various signaling pathways in which thrombopoietin (THPO)-MPL is dominant. Thrombopoiesis-stimulating agents could promote platelet production, showing therapeutic effects in different kinds of thrombocytopenia. Some thrombopoiesis-stimulating agents are currently used in clinical practices to treat thrombocytopenia. The others are not in clinical investigations to deal with thrombocytopenia but have potential in thrombopoiesis. Their potential values in thrombocytopenia treatment should be highly regarded. Novel drug screening models and drug repurposing research have found many new agents and yielded promising outcomes in preclinical or clinical studies. This review will briefly introduce thrombopoiesis-stimulating agents currently or potentially valuable in thrombocytopenia treatment and summarize the possible mechanisms and therapeutic effects, which may enrich the pharmacological armamentarium for the medical treatment of thrombocytopenia.
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Affiliation(s)
- Lejun Huang
- Division of Cell, Developmental and Integrative
Biology, School of Medicine, South China University of Technology,
Guangzhou, P.R. China
| | - Jianxuan Xu
- Division of Cell, Developmental and Integrative
Biology, School of Medicine, South China University of Technology,
Guangzhou, P.R. China
| | - Huaying Zhang
- Division of Cell, Developmental and Integrative
Biology, School of Medicine, South China University of Technology,
Guangzhou, P.R. China
| | - Mengfan Wang
- Division of Cell, Developmental and Integrative
Biology, School of Medicine, South China University of Technology,
Guangzhou, P.R. China
| | - Yiyue Zhang
- Division of Cell, Developmental and Integrative
Biology, School of Medicine, South China University of Technology,
Guangzhou, P.R. China
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Ankle NR, Desai R, Havaldar RR. Effect of Deviated Nasal Septum on Mean Platelet Volume: A Prospective Study. Indian J Otolaryngol Head Neck Surg 2022; 74:1216-1219. [PMID: 36452540 PMCID: PMC9702385 DOI: 10.1007/s12070-020-02289-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 11/24/2020] [Indexed: 10/22/2022] Open
Abstract
Nasal obstruction due to Deviated Nasal Septum (DNS) is a commonly encountered condition by the Otorhinolaryngologist. This leads to chronic hypoxia which in turn leads to stimulation of platelets. This change can be assessed by estimation of the Mean Platelet Volume (MPV) which is a commonly available investigation while ordering a haemogram. As there is a lot of conflicting data about the relationship between DNS and MPV, this study was undertaken to evaluate if there is a relationship between these two parameters. A 1-year observational study was done and after adhering to the inclusion and exclusion criteria, there were 50 cases of deviated nasal septum and 50 controls who attended the ENT Out-Patient Department of a tertiary care hospital who were evaluated. Blood was drawn and the Mean Platelet Volume was estimated. It was found that there was no statistical significance between the cases and controls. Contradictory to other studies done in literature, our study did not find any correlation. This could be due to the type of septal deviation cases that were part of our study. Hence, multicentric studies with larger samples need to be studied in order to establish sound conclusions.
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Affiliation(s)
- Nitin R. Ankle
- Department of ENT and Head & Neck Surgery, KAHER’s J. N. Medical College, Belagavi, Karnataka India
| | - Rohini Desai
- Department of ENT and Head & Neck Surgery, KAHER’s J. N. Medical College, Belagavi, Karnataka India
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Kinoshita N, Shima T, Terasaki K, Oya H, Katayama T, Matsumoto J, Mitsumoto Y, Mizuno M, Mizuno C, Hirohashi R, Sakai K, Okanoue T. Comparison of thrombocytopenia between patients with non-alcoholic fatty liver disease and those with hepatitis C virus-related chronic liver disease. Hepatol Res 2022; 52:677-686. [PMID: 35543116 DOI: 10.1111/hepr.13791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 05/01/2022] [Accepted: 05/05/2022] [Indexed: 02/08/2023]
Abstract
AIM Thrombocytopenia is widely recognized as a simple surrogate marker of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Thrombocytopenia of NAFLD has not been compared with that of hepatitis C virus-related chronic liver disease (CLD-C). Here, we examined whether there is any difference in the platelet counts between patients with NAFLD and CLD-C and investigated the underlying mechanisms. METHODS A total of 760 biopsy-confirmed NAFLD and 1171 CLD-C patients were enrolled. After stratification according to the liver fibrosis stage, platelet counts between NAFLD and CLD-C patients were compared. The platelet count, spleen size, serum albumin level, serum thrombopoietin level, and immature platelet fraction (IPF) value were also compared after covariate adjustment using propensity score (PS) matching. RESULTS The median platelet counts (×104 /μL) of NAFLD and CLD-C patients were 20.2 and 18.7 (p = 2.4 × 10-5 ) in F1; 20.0 and 14.5 (p = 2.1 × 10-12 ) in F2; 16.9 and 12.3 (p = 8.1 × 10-10 ) in F3; and 11.1 and 8.1 (p = 0.02) in F4, respectively. In the F3 group, NAFLD patients had a significantly higher platelet count and significantly smaller spleen volume than CLD-C patients. Although the serum thrombopoietin levels were comparable between NAFLD and CLD-C patients, the IPF value of NAFLD patients was significantly higher than that of CLD-C patients. CONCLUSIONS NAFLD patients had a significantly higher platelet count than CLD-C patients following stratification according to the liver fibrosis stage. The milder hypersplenism and higher platelet production in NAFLD than CLD-C may have contributed to this difference.
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Affiliation(s)
- Naohiko Kinoshita
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.,Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Kei Terasaki
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Hirohisa Oya
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Takayuki Katayama
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Junko Matsumoto
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Yasuhide Mitsumoto
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Masayuki Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | | | - Kyoko Sakai
- Clinical Laboratory, Saiseikai Suita Hospital, Suita, Japan.,Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
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9
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Menichelli D, Poli D, Antonucci E, Biccirè FG, Palareti G, Pignatelli P, Pastori D. Bleeding and mortality risk in patients implanted with mechanical prosthetic heart valves with and without thrombocytopenia. Insights from the nationwide PLECTRUM registry. Platelets 2022; 33:1018-1023. [PMID: 35021929 DOI: 10.1080/09537104.2022.2026909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Previous studies showed that mechanical prosthetic heart valve (MPHV) patients may develop thrombocytopenia, but its association with clinical outcomes has not been investigated. We enrolled 1,663 patients with available platelet count from the multicenter nationwide retrospective PLECTRUM registry to investigate the association of thrombocytopenia with all-cause mortality and major bleeding (MB) in patients implanted with MPHV. Thrombocytopenia was defined by platelet count <150 × 109/L. Overall, 44.9% of patients were women and the mean age was 56.7 years. At baseline, 184 (11.1%) patients had thrombocytopenia. Patients with thrombocytopenia were more frequently men and elderly. Platelet count showed an age-dependent decline in men but not in women. We found an increased risk of death in patients with age ≥ 65 years, with a low anticoagulation quality, concomitant arterial hypertension, heart failure, a higher INR range, or with thrombocytopenia (OR 1.739, 95%CI 1.048-2.886, p = .032). At multivariable logistic regression, patients with age ≥65 years, concomitant AF and thrombocytopenia (OR 1.907, 95%CI 1.219-2.983, p = .005) had an increased risk of MBs. In MPHV patients, thrombocytopenia is associated with an increased risk of death and MB. There is a growing need for a sex- and age-specific threshold to define platelet count in adult patients.
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Affiliation(s)
- Danilo Menichelli
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniela Poli
- Thrombosis Centre, Azienda Ospedaliero - Universitaria Careggi, Florence, Italy
| | | | - Flavio Giuseppe Biccirè
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.,Department of General and Specialized Surgery "Paride Stefanini", Sapienza University of Rome, Viale del Policlinico, Rome, Italy
| | | | - Pasquale Pignatelli
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniele Pastori
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
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Sheng H, Qiu Y, Xia X, Yi C, Lin J, Yang X, Huang F. Sexual Effect of Platelet-to-Lymphocyte Ratio in Predicting Cardiovascular Mortality of Peritoneal Dialysis Patients. Mediators Inflamm 2022; 2022:8760615. [PMID: 35027865 PMCID: PMC8752306 DOI: 10.1155/2022/8760615] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 12/09/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The study is aimed at exploring the relationship of platelet-to-lymphocyte (PLR), all-cause, and cardiovascular disease (CVD) mortality in peritoneal dialysis (PD) patients based on gender. METHODS A total of 1438 PD patients from January 1,2007 to December 31, 2014 in PD center at The First Affiliated Hospital, Sun Yat-sen University, were included. Patients were followed up until December 31, 2019. The endpoint was all-cause mortality and CVD mortality. Cox proportional hazards regression models were used to evaluate the association of PLR with all-cause and CVD mortality to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS After a median of 48.9 (interquartile range [IQR]: 23.4-79.3) months of follow-up, 406 (28.2%) patients died based on all-cause death, among which 200 (49.3%) patients died from CVD. In the multivariate Cox regression model, we found that PLR was independently related to an increased risk of CVD mortality only in female PD patients, with HR of 1.003 (95% CI: 1.001-1.006). Interaction test showed that the correlation between PLR level for all-cause and CVD mortality varied with gender (p = 0.042 and p = 0.012, respectively). CONCLUSION Higher PLR was associated with a higher risk of CVD mortality in female PD patients.
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Affiliation(s)
- Hui Sheng
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
| | - Yagui Qiu
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
| | - Xi Xia
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
| | - Chunyan Yi
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
| | - Jianxiong Lin
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
| | - Xiao Yang
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
| | - Fengxian Huang
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 58th, Zhongshan Road II, Guangzhou 510080, China
- Key Laboratory of Nephrology, National Health Commission of China and Guangdong Province, Guangzhou 510080, China
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11
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Ryalino C, Galag FR, Senapathi TA, Subagiartha M, Sutawan IKJ, Pradhana A. The effect of body temperature changes on inflammation response and patients’ comfort in patients undergoing laparotomy with general anesthesia. BALI JOURNAL OF ANESTHESIOLOGY 2022. [DOI: 10.4103/bjoa.bjoa_12_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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12
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Noh JY. Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications. Int J Mol Sci 2021; 22:ijms22179615. [PMID: 34502524 PMCID: PMC8431765 DOI: 10.3390/ijms22179615] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/02/2021] [Accepted: 09/02/2021] [Indexed: 12/13/2022] Open
Abstract
Platelets play a critical role in hemostasis and thrombus formation. Platelets are small, anucleate, and short-lived blood cells that are produced by the large, polyploid, and hematopoietic stem cell (HSC)-derived megakaryocytes in bone marrow. Approximately 3000 platelets are released from one megakaryocyte, and thus, it is important to understand the physiologically relevant mechanism of development of mature megakaryocytes. Many genes, including several key transcription factors, have been shown to be crucial for platelet biogenesis. Mutations in these genes can perturb megakaryopoiesis or thrombopoiesis, resulting in thrombocytopenia. Metabolic changes owing to inflammation, ageing, or diseases such as cancer, in which platelets play crucial roles in disease development, can also affect platelet biogenesis. In this review, I describe the characteristics of platelets and megakaryocytes in terms of their differentiation processes. The role of several critical transcription factors have been discussed to better understand the changes in platelet biogenesis that occur during disease or ageing.
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Affiliation(s)
- Ji-Yoon Noh
- Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
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13
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Aromatase is a novel neosubstrate of cereblon responsible for immunomodulatory drug-induced thrombocytopenia. Blood 2021; 135:2146-2158. [PMID: 32219443 DOI: 10.1182/blood.2019003749] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 03/09/2020] [Indexed: 01/06/2023] Open
Abstract
Immunomodulatory drugs (IMiDs) are key agents for the treatment of multiple myeloma and myelodysplastic syndrome with chromosome 5q deletion. IMiDs exert their pleiotropic effects through the recruitment of neosubstrates to cereblon, a substrate receptor of the E3 ubiquitin ligase complex; therefore, identification of cell-specific neosubstrates is important to understand the effects of IMiDs. In clinical practice, IMiDs induce thrombocytopenia, which frequently results in the discontinuation of IMiD treatment. In the current study, we sought to identify the molecular mechanism underlying thrombocytopenia induced by IMiD treatment. We found that IMiDs strongly impaired proplatelet formation, a critical step in functional platelet production, through the inhibition of autocrine estradiol signaling in human megakaryocytes. Furthermore, we identified aromatase, an indispensable enzyme for estradiol biosynthesis, as a novel neosubstrate of cereblon. IMiDs promoted the recruitment of aromatase to cereblon, resulting in the degradation of aromatase in a proteasome-dependent manner. Finally, aromatase was significantly degraded in the bone marrow of patients with multiple myeloma who developed thrombocytopenia with IMiD treatment. These data suggest that aromatase is a neosubstrate of cereblon that is responsible for IMiD-induced thrombocytopenia.
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14
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Kumar RS, Goyal N. Estrogens as regulator of hematopoietic stem cell, immune cells and bone biology. Life Sci 2021; 269:119091. [PMID: 33476629 DOI: 10.1016/j.lfs.2021.119091] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/03/2021] [Accepted: 01/11/2021] [Indexed: 12/11/2022]
Abstract
Hematopoietic stem cells provide continuous supply of all the immune cells, through proliferation and differentiation decisions. These decisions are controlled by local bone marrow environment as well as by long-range signals for example endocrine system. Sex dependent differential immunological responses have been described under homeostasis and disease conditions. Females show higher longevity than male counterpart that seems to depend on major female sex hormone, estrogen. There are four estrogens - Estrone (E1), estradiol (E2), Estriol (E3) and Estetrol (E4) that spatially and temporarily present during different female reproductive phases. In this review, we discussed recent updates describing the effects of estrogen on HSC, immune cells and in bone biology. Estradiol (E2) being a major/abundant estrogen is extensively investigated, while effects of other estrogens E1, E3 and E4 are started to unravel recently. Furthermore, clinical effect of estrogen as hormone therapy is discussed in HSC and immune cells perspectives. The data presented in this review is compiled by searches of PubMed, database of American Cancer Society (ACS). We have included article from September 1994 to March 2020 as covering all article in chronological order is not fissile so we included relevant article with substantial information in this specific area of research by using the search term (alone or in combination) estrogen, hematopoietic stem cell, immune cells, gender difference, estrone, estriol, estetrol, therapeutic application, pregnancy, effect on bone.
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Affiliation(s)
- Rupali Sani Kumar
- CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India.
| | - Neena Goyal
- CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India
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15
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Di Buduo CA, Soprano PM, Miguel CP, Perotti C, Del Fante C, Balduini A. A Gold Standard Protocol for Human Megakaryocyte Culture Based on the Analysis of 1,500 Umbilical Cord Blood Samples. Thromb Haemost 2020; 121:538-542. [PMID: 33160288 DOI: 10.1055/s-0040-1719028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Christian A Di Buduo
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Policlinico San Matteo Foundation, Pavia, Italy
| | - Paolo M Soprano
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Policlinico San Matteo Foundation, Pavia, Italy
| | - Carolina P Miguel
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Policlinico San Matteo Foundation, Pavia, Italy
| | - Cesare Perotti
- Immunohematology and Transfusion Service and Cell Therapy Unit, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Policlinico San Matteo Foundation, Pavia, Italy
| | - Claudia Del Fante
- Immunohematology and Transfusion Service and Cell Therapy Unit, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Policlinico San Matteo Foundation, Pavia, Italy
| | - Alessandra Balduini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Policlinico San Matteo Foundation, Pavia, Italy.,Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States
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16
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Haileslasie H, Tsegaye A, Teklehaymanot G, Belay G, Gebremariam G, Gebremichail G, Tesfanchal B, Kaleaye K, Legesse L, Adhanom G, Mardu F, Gebrewahd A, Tesfay G, Gebertsadik A. Community based hematological reference intervals among apparently healthy adolescents aged 12-17 years in Mekelle city, Tigrai, northern Ethiopia: A cross sectional study. PLoS One 2020; 15:e0234106. [PMID: 32925920 PMCID: PMC7489559 DOI: 10.1371/journal.pone.0234106] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 05/19/2020] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Hematological reference intervals are important in clinical and diagnostic management for the assessment of health and disease conditions. Hematological reference intervals are better to be established based on gender and age differences as these are among the main affecting factors. OBJECTIVE The aim of this study was to establish hematological reference intervals among apparently healthy adolescents aged 12-17 years in Mekelle City, Tigrai, Northern Ethiopia, 2019. METHOD A community-based cross-sectional study was conducted in 249 adolescents aged 12-17 years from December 2018 to May 2019. About 4ml of blood sample was collected from each study participant using vacutainer tube containing K2EDTA. Hematological parameters were analyzed using Sysmex KX-21N hematology analyzer (Sysmex Corporation Kobe, Japan). Data were entered and analyzed using SPSS version 23. Both parametric and non-parametric analyses were used to calculate the median and 95% of reference intervals. The 97.5th and 2.5th percentiles were calculated using descriptive statistics for the upper and lower reference limits of the study participants. Differences in reference intervals between male and female participants were evaluated using the Mann-Whitney U test. RESULT Among the 249 participants 122 (49%) were males and 127 (51%) were females with the median age of 14.5 (range 12 to 17) years were recruited in this study. The median and the 95% reference intervals of hematological parameters were determined. The 95% RIs were: Red blood cells (1012/Liter) 4.6-5.9 (Males) and 4.3-5.6 (Females), White blood cells (109/Liter) 2.9-9.6 (Males) and 3.4-10.2 (Females), Hemoglobin (g/dl) 12.6-17.1 (Males) and 12-15.4 (Females), Platelets (109/Liter) 138-364 (Males) and 151-462 (Females). Almost all of the hematological parameters showed significant differences (p<0.05) across gender. CONCLUSION The hematological reference intervals established in this study showed a difference based on gender. We suggest preparing and using distinct local reference intervals for males and females separately.
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Affiliation(s)
- Hagos Haileslasie
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
- * E-mail:
| | - Aster Tsegaye
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Gebreyohanes Teklehaymanot
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Mekelle University, Mekelle, Tigrai, Ethiopia
| | - Getachew Belay
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Gebreslassie Gebremariam
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Mekelle University, Mekelle, Tigrai, Ethiopia
| | - Gebremedhin Gebremichail
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Brhane Tesfanchal
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Kelali Kaleaye
- Laboratory Diagnostic, Research and Quality Assurance Directorate, Tigrai Health Research Institute, Mekelle, Tigrai, Ethiopia
| | - Lemlem Legesse
- Laboratory Diagnostic, Research and Quality Assurance Directorate, Tigrai Health Research Institute, Mekelle, Tigrai, Ethiopia
| | - Gebre Adhanom
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Fitsum Mardu
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Aderajew Gebrewahd
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Gebrehiwet Tesfay
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Adigrat University, Adigrat, Tigrai, Ethiopia
| | - Ataklti Gebertsadik
- Laboratory Diagnostic, Research and Quality Assurance Directorate, Tigrai Health Research Institute, Mekelle, Tigrai, Ethiopia
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17
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Poyrazoğlu HG, Öztürk AB. Predictive value of laboratory parameters in childhood migraine. Acta Neurol Belg 2020; 120:907-914. [PMID: 30840223 DOI: 10.1007/s13760-019-01106-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 02/26/2019] [Indexed: 12/20/2022]
Abstract
Migraine is a neurovascular disease characterized by inflammation of the cerebral and extra cerebral vessels and appears in the form of attacks. Although the pathophysiology of migraine is not fully known, the data obtained because of long-term studies reliably support the presence of a potential relationship between migraine pathogenesis and platelet biology. The aim of this study was to investigate the effect of migraine on MPV and other blood parameters as well as the relationship between the hematologic parameters and characteristics of the headache and whether they possess diagnostic value as inflammation and platelet biology play a fundamental role in the disorder. The study group consisted of 56 patients who were followed up and treated with a diagnosis of migraine and 45 healthy patients. The median creatinine, CRP and TSH values of the children in the migraine group were found to be statistically significantly higher than the healthy control group. Serum iron levels of the migraine group were found to be statistically significantly lower than the control group. No statistically significant difference was found between the two groups in terms of MPV. However, when we examined only the patient group, we found MPV to be statistically significantly higher in girls. Increased MPV and decreased serum iron levels may be related to migraine. More comprehensive studies including a larger population are required to evaluate the specific parameters that may guide the follow-up and treatment of the disorder with simple tests to be used in routine practice and to elucidate the underlying pathophysiology.
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18
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Sniffing out the aroma(tase) of drug-induced thrombocytopenia. Blood 2020; 135:2116-2117. [PMID: 32526021 DOI: 10.1182/blood.2020005969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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19
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Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-β1 Inhibition. Int J Mol Sci 2020; 21:ijms21114158. [PMID: 32532126 PMCID: PMC7312018 DOI: 10.3390/ijms21114158] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/31/2020] [Accepted: 06/04/2020] [Indexed: 12/14/2022] Open
Abstract
In chronic peritoneal diseases, mesothelial-mesenchymal transition is determined by cues from the extracellular environment rather than just the cellular genome. The transformation of peritoneal mesothelial cells and other host cells into myofibroblasts is mediated by cell membrane receptors, Transforming Growth Factor β1 (TGF-β1), Src and Hypoxia-inducible factor (HIF). This article provides a narrative review of the reprogramming of mesothelial mesenchymal transition in chronic peritoneal diseases, drawing on the similarities in pathophysiology between encapsulating peritoneal sclerosis and peritoneal metastasis, with a particular focus on TGF-β1 signaling and estrogen receptor modulators. Estrogen receptors act at the cell membrane/cytosol as tyrosine kinases that can phosphorylate Src, in a similar way to other receptor tyrosine kinases; or can activate the estrogen response element via nuclear translocation. Tamoxifen can modulate estrogen membrane receptors, and has been shown to be a potent inhibitor of mesothelial-mesenchymal transition (MMT), peritoneal mesothelial cell migration, stromal fibrosis, and neoangiogenesis in the treatment of encapsulating peritoneal sclerosis, with a known side effect and safety profile. The ability of tamoxifen to inhibit the transduction pathways of TGF-β1 and HIF and achieve a quiescent peritoneal stroma makes it a potential candidate for use in cancer treatments. This is relevant to tumors that spread to the peritoneum, particularly those with mesenchymal phenotypes, such as colorectal CMS4 and MSS/EMT gastric cancers, and pancreatic cancer with its desmoplastic stroma. Morphological changes observed during mesothelial mesenchymal transition can be treated with estrogen receptor modulation and TGF-β1 inhibition, which may enable the regression of encapsulating peritoneal sclerosis and peritoneal metastasis.
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20
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Kang J, Chang Y, Ahn J, Oh S, Koo D, Lee Y, Shin H, Ryu S. Neutrophil‐to‐lymphocyte ratio and risk of lung cancer mortality in a low‐risk population: A cohort study. Int J Cancer 2019; 145:3267-3275. [DOI: 10.1002/ijc.32640] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 08/08/2019] [Accepted: 08/21/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Jihoon Kang
- Department of Internal Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
- Department of Clinical Research Design & Evaluation, SAIHSTSungkyunkwan University Seoul Republic of Korea
| | - Jiin Ahn
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Sukjoong Oh
- Department of Internal Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Dong‐Hoe Koo
- Department of Internal Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Yun‐Gyoo Lee
- Department of Internal Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
- Department of Family Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of Medicine Seoul Republic of Korea
- Department of Clinical Research Design & Evaluation, SAIHSTSungkyunkwan University Seoul Republic of Korea
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21
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Lee HS, Koh IH, Kim HS, Kwon YJ. Platelet and white blood cell count are independently associated with sarcopenia: A nationwide population-based study. Thromb Res 2019; 183:36-44. [PMID: 31614293 DOI: 10.1016/j.thromres.2019.09.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 08/20/2019] [Accepted: 09/09/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Sarcopenia is attracting increasing attention due to its harmful impacts on health. Chronic inflammation is proposed to be a major cause of sarcopenia. Here, we aimed to identify whether white blood cell (WBC) and platelet count have independent roles in sarcopenia occurrence. METHOD AND MATERIALS This cross-sectional study analyzed 10,092 adults (4293 men and 5799 women) from the 2008-2011 Korea National Health and Nutrition Survey. Cut-off values for sarcopenia were defined as a skeletal muscle mass index <0.789 for men and <0.512 for women. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression analysis after adjusting for confounding variables. ROC curve analysis was used to evaluate the ability of platelet count and white blood cell count to discriminate the presence of sarcopenia. RESULTS After adjusting for possible confounders, the OR (95% CI) for sarcopenia occurrence according to platelet counts was 1.62 (1.20-2.19) for the T3 group in men and 1.72 (1.28-2.31) for the T3 group in women, relative to the lowest platelet count tertile. After adjusting for same confounders, the ORs (95% CI) for sarcopenia occurrence according to WBC counts was 1.86 (1.35-2.57) for the T3 group in men, and 2.36 (1.77-3.13) for the T3 group in women, relative to the lowest WBC count tertile. We also found independent significant associations between platelet count, WBC count, and sarcopenia. CONCLUSIONS Higher platelet and WBC counts within the normal range are each independently associated with sarcopenia in Korean men and women. The inclusion of platelet, WBC, or combined platelet and WBC counts significantly improved the power to discriminate sarcopenia.
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Affiliation(s)
- Hye Sun Lee
- Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Il-Hyun Koh
- Department of Orthopaedic Surgery, Yong-In Severance Hospital, Yonsei University College of Medicine, Gyeonggi, Republic of Korea.
| | - Hyoung-Sik Kim
- Department of Orthopaedic Surgery, Yong-In Severance Hospital, Yonsei University College of Medicine, Gyeonggi, Republic of Korea.
| | - Yu-Jin Kwon
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Family Medicine, Yong-In Severance Hospital, Yonsei University College of Medicine, Gyeonggi, Republic of Korea; Department of Medicine, Graduate School of Yonsei University College of Medicine, Seoul, Republic of Korea.
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22
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Li S, Lu J, Cheng W, Zhu J, Jin M. Factors Associated with Low Admission Platelet Count in Adults with Acute Aortic Dissection. Ann Thorac Cardiovasc Surg 2019; 25:142-148. [PMID: 30568075 PMCID: PMC6587131 DOI: 10.5761/atcs.oa.18-00187] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Purpose: Platelets are crucial components of the coagulation processes, and low admission platelet count (PLC) is associated with adverse clinical outcomes in patients with Stanford type A acute aortic dissection (AAD). Methods: A total of 130 consecutive patients undergoing Stanford type A AAD surgery in Beijing Anzhen Hospital were enrolled between January 2013 and July 2014. Preoperative clinical and laboratory data from patients were collected. Multiple regression analyses were used to determine the independent factors of low admission platelets. Results: Adjusted multiple regression analysis showed that age (β: −1.069, 95% confidence interval [CI]: −2.109, −0.029), sex (β: −29.973, 95% CI: −56.512, −3.433), tissue factor pathway inhibitor (TFPI; β: 0.197, 95% CI: 0.039, 0.354), fibrinogen degradation product (FDP) (β: −0.476, 95% CI: −0.879, −0.074), and attack time (β: 11.125, 95% CI: 7.963, 14.287) were significantly associated with admission PLC. Admission PLC increased with attack time up to the 3 days (β: 16.2, 95% CI: 12.1, 20.2). Conclusions: We found that increasing age, male patients, patients with lower serum levels of TFPI and higher serum levels of FDP, and patients with a shorter attack time were significantly associated with lower PLC at admission. Moreover, the turning point of attack time is 3 days after the onset of dissection.
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Affiliation(s)
- Shuwen Li
- Department of Anaesthesiology, Beijing AnZhen Hospital, Capital Medical University, Beijing, China
| | - Jiakai Lu
- Department of Anaesthesiology, Beijing AnZhen Hospital, Capital Medical University, Beijing, China
| | - Weiping Cheng
- Department of Anaesthesiology, Beijing AnZhen Hospital, Capital Medical University, Beijing, China
| | - Junming Zhu
- Department of Cardiology surgery, Beijing AnZhen Hospital, Capital Medical University, Beijing, China
| | - Mu Jin
- Department of Anaesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Wu L, Zou S, Wang C, Tan X, Yu M. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in Chinese Han population from Chaoshan region in South China. BMC Cardiovasc Disord 2019; 19:125. [PMID: 31132989 PMCID: PMC6537433 DOI: 10.1186/s12872-019-1110-7] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Accepted: 05/20/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are assumed to be prognostic factors in many diseases such as inflammatory diseases, cardiovascular diseases and cancer. However, NLR and PLR are race specific, it is important to determine the reference values of NLR and PLR in different races. The study aimed to investigate the reference range of NLR and PLR in Chinese Han population from Chaoshan region in South China. METHODS A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. Five thousand healthy adults aged 20-69 years were included. NLR and PLR were determined. RESULTS Of 5000 healthy adults, 2500 men and 2500 women were included. The mean NLR and PLR across all ages for men and women were 1.59 ± 0.59, 92.88 ± 28.70, 1.62 ± 0.64 and 108.02 ± 32.99, respectively. The 95% reference range of NLR in normal male and female are 0.43~2.75 and 0.37~2.87, PLR are 36.63~149.13 and 43.36~172.68, respectively. The female had a higher NLR at age 30~49 than the male while the NLR at age 60~69 was higher in male than in female. The PLR was higher in female than in male. CONCLUSION The study provides reference data on NLR and PLR from different age and sex groups in South China. NLR and PLR varied with age and sex.
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Affiliation(s)
- Lishan Wu
- Department of Cardiology, the First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong China
| | - Shan Zou
- Department of Cardiology, the First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong China
| | - Cantian Wang
- Department of Cardiology, the First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong China
| | - Xuerui Tan
- Department of Cardiology, the First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong China
| | - Min Yu
- Department of Cardiology, the First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong China
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Liu X, Wang H, Huang C, Meng Z, Zhang W, Li Y, Yu X, Du X, Liu M, Sun J, Zhang Q, Gao Y, Song K, Wang X, Zhao L, Fan Y. Association between platelet distribution width and serum uric acid in Chinese population. Biofactors 2019; 45:326-334. [PMID: 30697838 DOI: 10.1002/biof.1491] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/10/2018] [Accepted: 12/11/2018] [Indexed: 01/19/2023]
Abstract
Platelet distribution width (PDW) is a simple and inexpensive parameter, which could predict activation of coagulation efficiently. And it has been confirmed to have a significant role in many diseases. We aimed to explore the association between PDW and hyperuricemia in a large Chinese cohort. This cross-sectional study recruited 61,091 ostensible healthy participants (29,259 males and 31,832 females) after implementing exclusion criteria. Clinical data of the enrolled population included anthropometric measurements and serum parameters. Database was sorted by gender, and the association between PDW and hyperuricemia was analyzed after dividing PDW into quartiles. Crude and adjusted odds ratios of PDW for hyperuricemia with 95% confidence intervals were analyzed using binary logistic regression models. We found no significant difference in PDW values between the genders. Males showed significantly higher incidence of hyperuricemia than females. From binary logistic regression models, significant hyperuricemia risks only were demonstrated in PDW quartiles 2 and 3 in males (P < 0.05). This study displayed close association between PDW and hyperuricemia as a risk factor. It is meaningful to use PDW as a clinical risk predictor for hyperuricemia in males. © 2019 BioFactors, 45(3):326-334, 2019.
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Affiliation(s)
- Xiaoxia Liu
- Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Huiying Wang
- Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Chao Huang
- Hull York Medical School, University of Hull, Hull, UK
| | - Zhaowei Meng
- Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Wenjuan Zhang
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Yongle Li
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Xuefang Yu
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Xin Du
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Ming Liu
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Jinhong Sun
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Qing Zhang
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Ying Gao
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Kun Song
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Xing Wang
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Li Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China
| | - Yaguang Fan
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
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Rosinska J, Maciejewska J, Narożny R, Osztynowicz K, Raczak B, Michalak S, Watała C, Kozubski W, Łukasik M. Effect of acetylsalicylic acid intake on platelet derived microvesicles in healthy subjects. Platelets 2019; 31:206-214. [PMID: 30895834 DOI: 10.1080/09537104.2019.1588242] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Platelet-derived microvesicles (pMVs) are released from platelets in physiological and pathological conditions and exhibit a wide range of prothrombotic, antithrombotic, proatherogenic, and pro-inflammatory properties. Antiplatelet agents, such as acetylsalicylic acid (ASA), are widely used for the prevention and treatment of vascular diseases, but their impact on pMV release remains poorly understood and contradictory mainly because of discrepancies in the methodology and lack of well-standardized MV assessment protocols. The present study investigated the effects of ASA not only on total pMV release but also on their phenotypes defined using the surface expression of pro-inflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers in healthy subjects. Fifty healthy volunteers were enrolled in the study and received a daily dose of 150 mg ASA for 3 consecutive days. Circulating pMVs were characterized and quantified before and after the intervention period using flow cytometry. Serum levels of thromboxane B2 (TXB2) and whole blood impedance platelet aggregation under arachidonic acid (AA) stimulation were also investigated to assess ASA compliance. In general, ASA did not effect pMV numbers in healthy subjects despite its effective inhibition of platelet aggregation Moreover, in premenopausal women, we noticed an increase in the number of pMVs. Further studies are needed to assess whether dose modification of ASA or combinations or changes in antiplatelet therapy would reduce pMV formation, especially in patients with cardiovascular risk factors.
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Affiliation(s)
- Justyna Rosinska
- Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Maciejewska
- Laboratory of Flow Cytometry and Vascular Biology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Robert Narożny
- Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Krystyna Osztynowicz
- Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poznan, Poland
| | - Beata Raczak
- Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poznan, Poland
| | - Sławomir Michalak
- Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poznan, Poland
| | - Cezary Watała
- Department of Haemostasis and Haemostatic Disorders, Medical University, Lodz, Poland
| | - Wojciech Kozubski
- Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Maria Łukasik
- Laboratory of Flow Cytometry and Vascular Biology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
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Gou B, Cao H, Cheng X, Shang W, Xu M, Qian W. Prognostic value of mean platelet volume to plateletcrit ratio in patients with osteosarcoma. Cancer Manag Res 2019; 11:1615-1621. [PMID: 30863171 PMCID: PMC6388949 DOI: 10.2147/cmar.s193949] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Objective The objective of this study was to investigate the prognostic value of preoperative mean platelet volume to plateletcrit (MPV/PCT) ratio in patients with osteosarcoma. Materials and methods The retrospective study included 188 consecutive osteosarcoma patients who experienced neoadjuvant chemotherapy and surgical resection of tumor. The relationships between MPV/PCT and clinicopathological characteristics were analyzed. The Kaplan-Meier analysis and Cox regression proportional hazard model were applied to assess the prognostic value of MPV/PCT ratio. Results MPV/PCT ratio was found to be significantly associated with platelet count, platelet distribution width, and PCT (all P<0.001). Kaplan-Meier analysis showed that high MPV/PCT ratio (≥43.58) was associated with a prolonged disease-free survival (DFS, P=0.035). The multivariate Cox revealed that only good chemotherapy response was an independent predictor of better DFS in the overall population. However, the stratification analysis showed that a high MPV/PCT ratio (≥43.58) was indicated as an independent prognostic factor for a favorable DFS (HR =0.137, 95%CI =0.029-0.644, P=0.012) in the male osteosarcoma patients but not in female patients. Conclusion The high preoperative MPV/PCT ratio may serve as an independent prognostic factor for a favorable prognosis in male osteosarcoma patients. Further studies are needed to confirm the findings.
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Affiliation(s)
- Bo Gou
- Department of Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China,
| | - Hong Cao
- Department of Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China,
| | - Xinghua Cheng
- Department of Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China,
| | - Wei Shang
- Department of Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China,
| | - Mingqing Xu
- Department of Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China,
| | - Wei Qian
- Department of Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China,
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Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver. Mediterr J Hematol Infect Dis 2018; 10:e2018068. [PMID: 30416700 PMCID: PMC6223581 DOI: 10.4084/mjhid.2018.068] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 10/23/2018] [Indexed: 01/14/2023] Open
Abstract
In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis.
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Sultan N, Sharma SK. Prevalence of Low Platelet Count and Identification of Associating Determinants and Genetic Polymorphism in Healthy Individuals of Upper Assam, India. Indian J Hematol Blood Transfus 2018; 35:332-338. [PMID: 30988572 DOI: 10.1007/s12288-018-1007-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 08/31/2018] [Indexed: 12/18/2022] Open
Abstract
The purpose of the study was to assess the prevalence of low platelet count among the healthy population of upper Assam, India. The impact of socio-demographic features was moreover pointed to evaluate. Additionally, Mean platelet volume (MPV) and Interleukin-6 gene polymorphism (-174 G > C) were also determined to speculate their effect on the basal platelet count. For determination of hematological indices, CBC was done and genetic polymorphism was identified by ARMS-PCR technique. Out of 510 study subjects, 25.3% (n = 129) had low platelet count, and females were recorded with significantly higher mean platelet count as compared to their male counterpart (p < 0.001). A progressive decline in platelet count was observed with ageing and more significantly noticed in females across the various age groups (p < 0.001). The mean MPV was significantly higher in low platelet count group as compared to the normal group (p < 0.001). Both platelet count and MPV differed significantly among the individuals with varied ethnicity. An inverse correlation between platelet count and its volume was reported, and such observation was continued to persist in every age-group under the study. However, no significant differences were observed for other hematological indices between the studied groups except for platelet indices and RBC count. Moreover, the peripheral blood smear examined for cellular morphology and in vitro platelet clumping did not report any significant aberrancy. No significant penetrance of the risk allele was revealed in the studied groups. However, ARMS-PCR confirmed 6% (n = 8/129) of the low platelet count subjects with heterozygous for G allele. This happens to be the first description of low platelet count among the healthy population of upper Assam, where age, gender, ethnicity, and MPV are significantly associated with platelet count variation. Heterozygosity of the risk allele does not contribute to the low platelet count condition.
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Affiliation(s)
- Nasreen Sultan
- 1Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh, Assam 786004 India
| | - Santanu Kumar Sharma
- 2Indian Council of Medical Research-Regional Medical Research Centre, Northeast region, Post Box #105, Dibrugarh, Assam 786001 India
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Zhang Z, Chan TC, Guo C, Chang LY, Lin C, Chuang YC, Jiang WK, Ho KF, Tam T, Woo KS, Lau AKH, Lao XQ. Long-term exposure to ambient particulate matter (PM 2.5) is associated with platelet counts in adults. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2018; 240:432-439. [PMID: 29753251 DOI: 10.1016/j.envpol.2018.04.123] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 04/24/2018] [Accepted: 04/25/2018] [Indexed: 05/20/2023]
Abstract
BACKGROUND The prothrombotic effects of particulate matter (PM) may underlie the association of air pollution with increased risks of cardiovascular disease. This study aimed to investigate the association between long-term exposure to PM with an aerodynamic diameter ≤2.5 μm (PM2.5) and platelet counts, a marker of coagulation profiles. METHODS The study participants were from a cohort consisting of 362,396 Taiwanese adults who participated in a standard medical examination program between 2001 and 2014. Platelet counts were measured through Complete Blood Count tests. A satellite-based spatio-temporal model was used to estimate 2-year average ambient PM2.5 concentration at each participant's address. Mixed-effects linear regression models were used to investigate the association between PM2.5 exposure and platelet counts. RESULTS This analysis included 175,959 men with 396,248 observations and 186,437 women with 397,877 observations. Every 10-μg/m3 increment in the 2-year average PM2.5 was associated with increases of 0.42% (95% CI: 0.38%, 0.47%) and 0.49% (95% CI: 0.44%, 0.54%) in platelet counts in men and women, respectively. A series of sensitivity analyses, including an analysis in participants free of cardiometabolic disorders, confirmed the robustness of the observed associations. Baseline data analyses showed that every 10-μg/m3 increment in PM2.5 was associated with higher risk of 17% and 14% of having elevated platelet counts (≥90th percentile) in men and women, respectively. CONCLUSIONS Long-term exposure to PM2.5 appears to be associated with increased platelet counts, indicating potential adverse effects on blood coagulability.
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Affiliation(s)
- Zilong Zhang
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
| | - Ta-Chien Chan
- Research Center for Humanities and Social Sciences, Academia Sinica, Taiwan
| | - Cui Guo
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
| | - Ly-Yun Chang
- MJ Health Research Foundation, MJ Group, Taiwan; Institute of Sociology, Academia Sinica, Taiwan
| | - Changqing Lin
- Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology, Hong Kong; Division of Environment and Sustainability, The Hong Kong University of Science and Technology, Hong Kong
| | | | | | - Kin Fai Ho
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
| | - Tony Tam
- Department of Sociology, The Chinese University of Hong Kong, Hong Kong
| | - Kam S Woo
- Institute of Future Cities, The Chinese University of Hong Kong, Hong Kong
| | - Alexis K H Lau
- Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology, Hong Kong; Division of Environment and Sustainability, The Hong Kong University of Science and Technology, Hong Kong
| | - Xiang Qian Lao
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong; Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, China.
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Wang MC, Huang CE, Lin MH, Yang YH, Lu CH, Chen PT, Wu YY, Tsou HY, Hsu CC, Chen CC. Impacts of demographic and laboratory parameters on key hematological indices in an adult population of southern Taiwan: A cohort study. PLoS One 2018; 13:e0201708. [PMID: 30071080 PMCID: PMC6072090 DOI: 10.1371/journal.pone.0201708] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 07/20/2018] [Indexed: 12/14/2022] Open
Abstract
Studies in Caucasians have shown that values of hematological indices could be affected by a wide variety of factors. However, parallel work in other ethnical populations, particularly from the Asia-Pacific region, is lacking. Therefore, we designed this study to explore the association between clinical/laboratory parameters and hemogram levels. Adult individuals who came to our hospital for health exams were screened. Information on demographics and laboratory profiles was obtained. We analyzed the impacts of these parameters on the variation of hemogram. Overall, 26,497 adults were included in the current analysis after excluding those with abnormal hemogram. Multivariate regression analysis showed increasing age and male gender negatively affected the number of platelets, whereas a higher serum apolipoprotein B level was associated with an elevated platelet count. Gender and serum albumin level were the major determinants of variation in hemoglobin level. A modestly increased white cell count was seen in men as well as individuals with elevated apolipoprotein B levels, but it was inversely correlated with changes in age and serum albumin levels. Conversely, some variables, although statistically significantly associated with the hematological indices, only provided a trivial explanation for the heterogeneity observed. We further established predictive models for the approximate estimation of hematological indices in healthy adults. Our data indicate that age, gender, and serum levels of apolipoprotein B and albumin affect hematological indices in various ways. We also demonstrate that variation in hemogram could be successfully predicted by a number of clinical and laboratory parameters.
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Affiliation(s)
- Ming-Chung Wang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Cih-En Huang
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Meng-Hung Lin
- Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Hsu Yang
- Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chang-Hsien Lu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ping-Tsung Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Ying Wu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Hsing-Yi Tsou
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chia-Chen Hsu
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chih-Cheng Chen
- Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- * E-mail:
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Wang LR, Zhou YF, Zhou YJ, Zhang SH, Liu WY, Wu SJ, Van Poucke S, Zheng MH. Elevation of plateletcrit increasing the risk of non-alcoholic fatty liver disease development in female adults: A large population-based study. Clin Chim Acta 2017; 474:28-33. [PMID: 28866118 DOI: 10.1016/j.cca.2017.08.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 07/17/2017] [Accepted: 08/28/2017] [Indexed: 01/01/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the one of the most common form of chronic liver disease in China, so it is important to apply bio-marker in predict the development of NAFLD. AIMS This study aims to evaluate association between plateletcrit (PCT) and non-alcoholic fatty liver disease (NAFLD) in Chinese female adults. METHODS NAFLD was defined as per ultrasound in this study and 9737 NAFLD-free female subjects from Wenzhou People's Hospital were followed for five years in average in the study. The determination of NAFLD PCT quartiles (Q1 to Q4) were defined: 0-0.16, 0.17-0.18, 0.19-0.21, ≥0.22. With Q1 used as reference, 95% confidence intervals (CIs) and hazard ratios (HRs) in different models were computed across each quartile. RESULTS From Q1 to Q4, the incidence ratios (95% CIs) were 8.30 (7.14-9.47), 11.51 (10.12-12.89), 12.68 (11.47-13.89) and 16.46 (15.03-17.88). Simply considering PCT, in the longitudinal population, values in Q2, Q3 and Q4 had HRs (95% CIs) are 1.51 (1.25-1.84), 1.72 (1.44-2.06) and 2.34 (1.96-2.79) versus Q1. After adjusting for all known confounding variables, values in Q2, Q3 and Q4 had HRs (95% CIs) of 1.31 (1.08-1.60), 1.30 (1.09-1.56) and 1.54 (1.29-1.84) in females compared with Q1. CONCLUSIONS We reported that elevated serum PCT levels are considered as an independently significant predictor for NAFLD development in females. The high PCT level contributes to the development of NAFLD.
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Affiliation(s)
- Li-Ren Wang
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Yi-Fan Zhou
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Yu-Jie Zhou
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Shu-Hao Zhang
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Wen-Yue Liu
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Sheng-Jie Wu
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Cardiovascular Medicine, The Heart Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Sven Van Poucke
- Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Ming-Hua Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China.
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A novel mode of stimulating platelet formation activity in megakaryocytes with peanut skin extract. J Nat Med 2017; 72:211-219. [PMID: 29019067 DOI: 10.1007/s11418-017-1135-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 09/18/2017] [Indexed: 10/18/2022]
Abstract
We report in this study novel biochemical activities of peanut skin extract (PEXT) on thrombocytopoiesis. Peanut skin, derived from Arachis hypogaea L., is a traditional Chinese medicine that is used to treat chronic hemorrhage. We have shown that oral administration of PEXT increases the peripheral platelet levels in mice. Recently, we reported a liquid culture system that is useful for investigating megakaryocytopoiesis and thrombocytopoiesis from human CD34+ cells. In this liquid culture system, PEXT was shown to enhance the formation of CD41+/DAPI- cells (platelets), but had no effect on the formation of CD41+/DAPI+ cells (megakaryocytes) or on the DNA content. Furthermore, PEXT selectively stimulated proplatelet formation from cultured mature megakaryocytes and phorbol 12-myristate 13 acetate (PMA)-induced formation of platelet-like particles from Meg01 cells. Despite having no influence on the formation of megakaryocyte colony forming units (CFUs), PEXT increased the size of megakaryocytes during their development from CD34+ cells. PEXT showed no effect on the GATA-1 and NF-E2 mRNA levels, which are known to play an important role in thrombocytopoiesis and, based on the results of a pMARE-Luc (pGL3-MARE-luciferase) assay, had no influence on NF-E2 activation in Meg01 cells. These results suggest that PEXT accelerates proplatelet formation from megakaryocytes but does not influence the development of hematopoietic stem cells into megakaryocytes.
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Zhou P, Meng Z, Liu M, Ren X, Zhu M, He Q, Zhang Q, Liu L, Song K, Jia Q, Tan J, Li X, Liu N, Hu T, Upadhyaya A. The associations between leukocyte, erythrocyte or platelet, and metabolic syndrome in different genders of Chinese. Medicine (Baltimore) 2016; 95:e5189. [PMID: 27858856 PMCID: PMC5591104 DOI: 10.1097/md.0000000000005189] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Leukocyte, erythrocyte or platelet and metabolic syndrome (MS) are closely correlated, and there exist gender differences. We aimed to explore the associations between the hematological parameters and MS in different genders of Chinese. This cross-sectional study included 32,900 participants (20,733 males, 12,167 females) who were enrolled in a health examination. Clinical data including anthropometric measurements and serum parameters were collected. The associations between hematological parameters and MS of both genders were analyzed separately. Odds ratio (OR) of MS was calculated by binary logistic regression models. All hematological parameters were related to MS. With leukocyte and erythrocyte counts rising, the risks of developing MS increased in both genders, which was more obvious in women. For instance, in model 3, the ORs of MS in leukocyte quartiles in females were from 1.333 to 2.045 (P < 0.01), while in males, from 1.238 to 1.675 (P < 0.01). Platelet seemed as a protective factor in males. Model 1 and model 3 in quartile 2 demonstrated ORs of 0.922 (P < 0.05) and 0.912 (P < 0.05). However, platelet acted as risk factor in female. For instance, the ORs were 1.253 (P < 0.01), 1.461 (P < 0.01), and 1.322 (P < 0.01) in platelet quartile 4 of all 3 models in female. Gender has influences on the associations between leukocyte, erythrocyte or platelet, and MS. In both genders, higher levels of leukocyte and erythrocyte increased risks of MS. For men, platelet was a protective factor, but for women, platelet seemed as a risk factor.
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Affiliation(s)
| | - Zhaowei Meng
- Department of Nuclear Medicine
- Correspondence: Zhaowei Meng, Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road No. 154, Heping District, Tianjin, 300052, Peoples Republic of China (e-mail: )
| | - Ming Liu
- Department of Endocrinology and Metabolism
| | | | - Mei Zhu
- Department of Endocrinology and Metabolism
| | - Qing He
- Department of Endocrinology and Metabolism
| | - Qing Zhang
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, Peoples Republic of China
| | - Li Liu
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, Peoples Republic of China
| | - Kun Song
- Department of Health Management, Tianjin Medical University General Hospital, Tianjin, Peoples Republic of China
| | | | | | - Xue Li
- Department of Nuclear Medicine
| | - Na Liu
- Department of Nuclear Medicine
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Du C, Xu Y, Yang K, Chen S, Wang X, Wang S, Wang C, Shen M, Chen F, Chen M, Zeng D, Li F, Wang T, Wang F, Zhao J, Ai G, Cheng T, Su Y, Wang J. Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1. Leukemia 2016; 31:945-956. [DOI: 10.1038/leu.2016.285] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 09/13/2016] [Accepted: 09/14/2016] [Indexed: 12/21/2022]
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35
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Schneider L, Mischke R. Platelet variables in healthy dogs: reference intervals and influence of age, breed and sex. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/s00580-016-2305-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Bora K, Jitani AK, Raphael V, Ruram AA, Borah P, Khonglah Y. Association between lipid profile and platelet indices: the importance of considering the influence of lipid profile while evaluating the clinical utility of platelet indices. Int J Lab Hematol 2016; 38:e80-3. [DOI: 10.1111/ijlh.12511] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- K. Bora
- North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences; Shillong India
| | - A. K. Jitani
- North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences; Shillong India
| | - V. Raphael
- North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences; Shillong India
| | - A. A. Ruram
- North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences; Shillong India
| | - P. Borah
- State Biotech Hub (SBT Hub) and Bioinformatics Infrastructure Facility (BIF); College of Veterinary Science; Guwahati India
| | - Y. Khonglah
- North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences; Shillong India
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Abdelbaset-Ismail A, Suszynska M, Borkowska S, Adamiak M, Ratajczak J, Kucia M, Ratajczak MZ. Human haematopoietic stem/progenitor cells express several functional sex hormone receptors. J Cell Mol Med 2016; 20:134-146. [PMID: 26515267 PMCID: PMC4717849 DOI: 10.1111/jcmm.12712] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Evidence has accumulated that murine haematopoietic stem/progenitor cells (HSPCs) share several markers with the germline, a connection supported by recent reports that pituitary and gonadal sex hormones (SexHs) regulate development of murine HSPCs. It has also been reported that human HSPCs, like their murine counterparts, respond to certain SexHs (e.g. androgens). However, to better address the effects of SexHs, particularly pituitary SexHs, on human haematopoiesis, we tested for expression of receptors for pituitary SexHs, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), as well as the receptors for gonadal SexHs, including progesterone, oestrogens, and androgen, on HSPCs purified from human umbilical cord blood (UCB) and peripheral blood (PB). We then tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. In parallel, we tested the effect of SexHs on human mesenchymal stromal cells (MSCs). Finally, based on our observation that at least some of the UCB-derived, CD45(-) very small embryonic-like stem cells (VSELs) become specified into CD45(+) HSPCs, we also evaluated the expression of pituitary and gonadal SexH receptors on these cells. We report for the first time that human HSPCs and VSELs, like their murine counterparts, express pituitary and gonadal SexH receptors at the mRNA and protein levels. Most importantly, SexH if added to suboptimal doses of haematopoietic cytokines and growth factors enhance clonogenic growth of human HSPCs as well as directly stimulate proliferation of MSCs.
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Affiliation(s)
- Ahmed Abdelbaset-Ismail
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
| | - Malwina Suszynska
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
- Department of Physiology, Pomeranian Medical University, Szczecin, Poland
| | - Sylwia Borkowska
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
| | - Mateusz Adamiak
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
| | - Janina Ratajczak
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
| | - Magda Kucia
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
- Department of Regenerative Medicine, Medical University of Warsaw, Warszawa, Poland
- Department of Physiology, Pomeranian Medical University, Szczecin, Poland
| | - Mariusz Z Ratajczak
- Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
- Department of Regenerative Medicine, Medical University of Warsaw, Warszawa, Poland
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yong M. Large Population Study for Age- and Gender- Related Variations of Platelet Indices in Southwest China Healthy Adults. ACTA ACUST UNITED AC 2015. [DOI: 10.15406/htij.2015.01.00023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study. Blood 2015; 127:251-9. [PMID: 26518434 DOI: 10.1182/blood-2015-07-660308] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 10/19/2015] [Indexed: 12/29/2022] Open
Abstract
Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (β, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (β, 0.178; 95% CI, 0.128 to 0.229), hypertension (β, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (β, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV in males only. Intake of oral contraceptives (β, 0.150; 95% CI, 0.0649 to 0.236) and menstruation (β, 0.123; 95% CI, 0.0231 to 0.224) were strongly associated with higher MPV in females. Seven single nucleotide polymorphisms (SNPs) for females and 4 SNPs for males were associated with higher MPV. The full model, including age, CVRFs, laboratory parameters, medications, and genetic variation, explained 20.4% of the MPV variance in females and 18.6% in males. The curves of cumulative mortality, stratified for sex, showed worse survival for males only with MPV > 9.96 fL vs MPV ≤ 9.96 fL (P < .0001). This study provides evidence for heterogeneity in the profile of determinants for MPV between sexes. The observed interactions between genetic variability, CVRFs, and MPV and its association with the development of cardiovascular disease or thrombotic risk need to be further investigated.
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Dorn DC, Dorn A. Stem cell autotomy and niche interaction in different systems. World J Stem Cells 2015; 7:922-944. [PMID: 26240680 PMCID: PMC4515436 DOI: 10.4252/wjsc.v7.i6.922] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells (homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche (hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion (E-cadherin) and the direction of asymmetrical GSC division - as they were found in Drosophila - can hardly be translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon pruning and dying-back degeneration in neurodegenerative diseases. Especially the hypothesis of an existing evolutionary conserved “autodestruction program” in axons that might also be active in GSC projections appears attractive. Investigations on the underlying signaling pathways have to be carried out. There are two other well known cases of programmed cell autotomy: the enucleation of erythroblasts in the process of erythrocyte maturation and the segregation of thousands of thrombocytes (platelets) from one megakaryocyte. Both progenitor cell types - erythroblasts and megakaryocytes - are associated with a niche in the bone marrow, erythroblasts with a macrophage, which they surround, and the megakaryocytes with the endothelial cells of sinusoids and their extracellular matrix. Although the regulatory mechanisms may be specific in each case, there is one aspect that connects all described processes of programmed cell autotomy and neuronal autodestruction: apoptotic pathways play always a prominent role. Studies on the role of male GSC autotomy in stem cell-niche interaction have just started but are expected to reveal hitherto unknown ways of signal exchange. Spermatogenesis in mammals advance our understanding of insect spermatogenesis. Mammal and insect spermatogenesis share some broad principles, but a comparison of the signaling pathways is difficult. We have intimate knowledge from Drosophila, but of almost no other insect, and we have only limited knowledge from mammals. The discovery of stem cell autotomy as part of the interaction with the niche promises new general insights into the complicated stem cell-niche interdependence.
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Sloan A, Gona P, Johnson AD. Cardiovascular correlates of platelet count and volume in the Framingham Heart Study. Ann Epidemiol 2015; 25:492-8. [PMID: 25771288 PMCID: PMC4457710 DOI: 10.1016/j.annepidem.2015.01.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Revised: 01/09/2015] [Accepted: 01/21/2015] [Indexed: 01/13/2023]
Abstract
PURPOSE Platelet count and volume are inexpensive, routinely assayed biomarkers associated with cardiovascular health, but specific relationships among platelet indices, cardiovascular risk factors, and disease warrant further investigation. The purpose of this study was to understand associations among platelet count, volume, and 20 cardiovascular health-related variables in the Framingham Heart Study (FHS). METHODS Cross-sectional analyses were performed on platelet count and volume associations with cardiovascular health indicators in three FHS cohorts (original n = 964, offspring n = 2699, and third generation n = 2419) using multivariate linear regression analysis. Time-to-event analysis was used for cardiovascular disease-related event incidences using Kaplan-Meier plots and Cox proportional hazards regression adjusted for age and sex. RESULTS Results were concordant with the hypothesis that higher platelet counts are associated with less favorable cardiovascular risk profiles, although mean platelet volume associations were weaker. In our analysis, increased platelet count across FHS cohorts was consistently associated with smoking, triglycerides, low-density lipoprotein, and total cholesterol levels. Some associations with platelet count appeared sex dependent. CONCLUSIONS Significant associations of common blood platelet measurements are observed with sex and cardiovascular risk factors, namely smoking and lipids. Research is warranted to confirm these relationships in other cohorts, evaluate differences by ethnicity, and examine longitudinal effects on disease risk.
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Affiliation(s)
- Arielle Sloan
- Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA; Department of Health Science, Brigham Young University, Provo, UT
| | - Philimon Gona
- Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA; College of Nursing and Health Sciences, University of Massachusetts Boston, Boston
| | - Andrew D Johnson
- Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA.
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42
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Gasiorek JJ, Blank V. Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells. Cell Mol Life Sci 2015; 72:2323-35. [PMID: 25721735 PMCID: PMC11114048 DOI: 10.1007/s00018-015-1866-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 01/27/2015] [Accepted: 02/16/2015] [Indexed: 01/01/2023]
Abstract
The NFE2 transcription factor was identified over 25 years ago. The NFE2 protein forms heterodimers with small MAF proteins, and the resulting complex binds to regulatory elements in a large number of target genes. In contrast to other CNC transcription family members including NFE2L1 (NRF1), NFE2L2 (NRF2) and NFE2L3 (NRF3), which are widely expressed, earlier studies had suggested that the major sites of NFE2 expression are hematopoietic cells. Based on cell culture studies it was proposed that this protein acts as a critical regulator of globin gene expression. However, the knockout mouse model displayed only mild erythroid abnormalities, while the major phenotype was a defect in megakaryocyte biogenesis. Indeed, absence of NFE2 led to severely impaired platelet production. A series of recent data, also summarized here, shed new light on the various functional roles of NFE2 and the regulation of its activity. NFE2 is part of a complex regulatory network, including transcription factors such as GATA1 and RUNX1, controlling megakaryocytic and/or erythroid cell function. Surprisingly, it was recently found that NFE2 also has a role in non-hematopoietic tissues, such as the trophoblast, in which it is also expressed, as well as the bone, opening the door to new research areas for this transcription factor. Additional data showed that NFE2 function is controlled by a series of posttranslational modifications. Important strides have been made with respect to the clinical significance of NFE2, linking this transcription factor to hematological disorders such as polycythemias.
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Affiliation(s)
- Jadwiga J. Gasiorek
- Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte Sainte-Catherine, Montreal, QC H3T 1E2 Canada
- Department of Medicine, McGill University, Montreal, QC Canada
| | - Volker Blank
- Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte Sainte-Catherine, Montreal, QC H3T 1E2 Canada
- Department of Medicine, McGill University, Montreal, QC Canada
- Department of Physiology, McGill University, Montreal, QC Canada
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Affiliation(s)
- Carlo L Balduini
- Department of Internal Medicine, University of Pavia - IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Patrizia Noris
- Department of Internal Medicine, University of Pavia - IRCCS Policlinico San Matteo Foundation, Pavia, Italy
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44
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Effect of Deviated Nasal Septum on Mean Platelet Volume: A Prospective Study. Indian J Otolaryngol Head Neck Surg 2014; 66:437-40. [PMID: 26396958 DOI: 10.1007/s12070-014-0748-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Accepted: 07/07/2014] [Indexed: 10/24/2022] Open
Abstract
In E.N.T clinical practice, patients with nasal obstruction due to deviated nasal septum is a common presentation. Nasal airway obstruction is a common cause of upper airway obstruction further leading to obstructive and hypoxic manifestations. Mean platelet volume (MPV) levels increase in hypoxic conditions. MPV is one of the platelet activation index which reflects the platelet production rate. Present prospective study conducted in the department of Otorhinolaryngology and Head and Neck surgery, Gandhi Medical College and Hamidia Hospital, Bhopal, on 63 patients with the clinical evidence of DNS and 63 healthy age matched subjects as control group, aimed to evaluate the relationship between MPV levels and nasal obstruction due to deviated nasal septum (DNS). The diagnosis of patients with DNS was based on anterior rhinoscopy and endoscopic nasal examination. Blood samples were collected before surgical correction. In present study, the authors found that there is preponderance of DNS in the age group of 25-45 years being the most active age group, males having the higher incidence. Majority of cases of DNS being left sided and of obstructed type. MPV were significantly higher in patients with DNS than the control group. Among the cases MPV being higher in females and in the impacted type of DNS. Present study reemphasized the concept that MPV is increased in chronic nasal obstruction due to DNS and this increase is in accordance with the severity of DNS.
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45
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Chen YL, Hung YJ, He CT, Lee CH, Hsiao FC, Pei D, Hsieh CH. Platelet count can predict metabolic syndrome in older women. Platelets 2014; 26:31-7. [PMID: 24512307 DOI: 10.3109/09537104.2014.880415] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Platelet count (PC) has been found to be related to the metabolic syndrome (MetS). However, the role of PC on MetS remained unclear. In order to evaluate the relationship between PC and MetS components cross-sectionally and determine the optimal cutoff PCs for predicting the subsequent risk of MetS development with sex specificity, two stages included cross-sectional (stage 1) and prospective (stage 2) cohort study were conducted. Stage 1 involved 10 579 subjects aged ≥60 years, of which 7718 subjects advanced to stage 2 with a mean 3.8 year follow-up were enrolled. The MetS components and PC were determined. The PC cutoffs for higher chances of developing MetS in stage 1 were calculated using receiver operating characteristic (ROC) curve analyses. In stage 2, non-MetS subjects were classified into high-PC (HPC) and low-PC (LPC) groups according to the cutoff values from stage 1. We examined the difference of future MetS incidence and calculated the odds ratio (OR) between these two groups. In stage 1, multiple regression showed that age and triglyceride (both sexes) and waist circumstance and high-density lipoprotein cholesterol (only women) were independently correlated with PC. There was significant difference in the area under the ROC curve (AUC) only of HPC women, which exceeded the standard curve (AUC = 0.542, p < 0.001), with a cutoff PC of 223 × 10(3)/μl. HPC women had an OR of 1.287 (95% confidence interval: 1.135-1.461) of developing MetS after 3.8 years. The Kaplan-Meier curve demonstrated a higher incidence of MetS development in HPC women. In conclusion, our results suggest that PC was associated with MetS with sex effects. Most of the MetS components were independent factors for increasing PC, and the risk for subsequent development of MetS was noted when PC >223 × 10(3)/μl in elderly women.
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Affiliation(s)
- Yen-Lin Chen
- Department of Pathology, Cardinal Tien Hospital , New Taipei City, Taiwan , R.O.C
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Tijssen MR, Ghevaert C. Transcription factors in late megakaryopoiesis and related platelet disorders. J Thromb Haemost 2013; 11:593-604. [PMID: 23311859 PMCID: PMC3824237 DOI: 10.1111/jth.12131] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2013] [Indexed: 01/09/2023]
Abstract
Cell type-specific transcription factors regulate the repertoire of genes expressed in a cell and thereby determine its phenotype. The differentiation of megakaryocytes, the platelet progenitors, from hematopoietic stem cells is a well-known process that can be mimicked in culture. However, the efficient formation of platelets in culture remains a challenge. Platelet formation is a complicated process including megakaryocyte maturation, platelet assembly and platelet shedding. We hypothesize that a better understanding of the transcriptional regulation of this process will allow us to influence it such that sufficient numbers of platelets can be produced for clinical applications. After an introduction to gene regulation and platelet formation, this review summarizes the current knowledge of the regulation of platelet formation by the transcription factors EVI1, GATA1, FLI1, NFE2, RUNX1, SRF and its co-factor MKL1, and TAL1. Also covered is how some platelet disorders including myeloproliferative neoplasms, result from disturbances of the transcriptional regulation. These disorders give us invaluable insights into the crucial role these transcription factors play in platelet formation. Finally, there is discussion of how a better understanding of these processes will be needed to allow for efficient production of platelets in vitro.
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Affiliation(s)
- M R Tijssen
- Department of Haematology, University of CambridgeUK
- Department of Haematology, University of Cambridge, and NHS Blood and TransplantCambridge, UK
| | - C Ghevaert
- Department of Haematology, University of Cambridge, and NHS Blood and TransplantCambridge, UK
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Biino G, Santimone I, Minelli C, Sorice R, Frongia B, Traglia M, Ulivi S, Di Castelnuovo A, Gögele M, Nutile T, Francavilla M, Sala C, Pirastu N, Cerletti C, Iacoviello L, Gasparini P, Toniolo D, Ciullo M, Pramstaller P, Pirastu M, de Gaetano G, Balduini CL. Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data. PLoS One 2013; 8:e54289. [PMID: 23382888 PMCID: PMC3561305 DOI: 10.1371/journal.pone.0054289] [Citation(s) in RCA: 182] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 12/10/2012] [Indexed: 02/06/2023] Open
Abstract
Background and Objectives Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150–400×109 platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. Methods We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. Results Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×109/L in children (176–452), adult men (141–362), adult women (156–405), old men (122–350) and, old women (140–379). Moreover, we calculated an “extended” reference interval that takes into account the differences in platelet count observed in different geographic areas. Conclusions The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy.
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Affiliation(s)
- Ginevra Biino
- Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy.
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Chronic estradiol treatment reduces platelet responses and protects mice from thromboembolism through the hematopoietic estrogen receptor α. Blood 2012; 120:1703-12. [PMID: 22776819 DOI: 10.1182/blood-2012-01-405498] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Although estrogens are known to have a deleterious effect on the venous thrombosis risk and a preventive action on the development of arterial atheroma, their effect on platelet function in vivo remains unclear. Here, we demonstrate that a chronic high physiologic level of estradiol (E2) in mice leads to a marked decrease in platelet responsiveness ex vivo and in vivo compared with ovariectomized controls. E2 treatment led to increased bleeding time and a resistance to thromboembolism. Hematopoietic chimera mice harboring a selective deletion of estrogen receptors (ERs) α or β were used to demonstrate that the effects of E2 were exclusively because of hematopoietic ERα. Within ERα the activation function-1 domain was not required for resistance to thromboembolism, as was previously shown for atheroprotection. This domain is mandatory for E2-mediated reproductive function and suggests that this role is controlled independently. Differential proteomics indicated that E2 treatment modulated the expression of platelet proteins including β1 tubulin and a few other proteins that may impact platelet production and activation. Overall, these data demonstrate a previously unrecognized role for E2 in regulating the platelet proteome and platelet function, and point to new potential antithrombotic and vasculoprotective therapeutic strategies.
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de Gaetano G, Santimone I, Gianfagna F, Iacoviello L, Cerletti C. Variability of platelet indices and function: acquired and genetic factors. Handb Exp Pharmacol 2012:395-434. [PMID: 22918740 DOI: 10.1007/978-3-642-29423-5_16] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Each individual has an inherent variable risk of bleeding linked to genetic or acquired abnormal platelet number or platelet dysfunction. In contrast, it is less obvious that the variability of platelet phenotypes (number, mean platelet volume, function) may contribute to the variable individual risk of thrombosis. Interindividual variability of platelet indices or function may be either due to acquired factors, such as age, sex, metabolic variables, smoke, dietary habits, and ongoing inflammation, or due to genetic factors. Acquired variables explain a small portion of the heterogeneity of platelet parameters. Genetic factors, instead, appear to play a major role, although a consistent portion of such a genetic variance has not yet been attributed to any specific genetic factor, possibly due to the high number of DNA loci potentially involved and to the limited effect size of each individual SNP. A portion of variance remains thus unexplained, also due to variability of test performance. A major contradiction in present platelet knowledge is, indeed, the difficulty to reconcile the universally accepted importance of platelet indices or function and the lack of reliable platelet parameters in cardiovascular risk prediction models. Trials on antiplatelet drugs were generally designed to select a homogeneous sample, whose results could be applied to an "average subject," tending to exclude the deviation/extreme values. As the current indications for antiplatelet treatment in primary or secondary prevention of ischemic vascular disease still derive from the results of such clinical trials where platelet function and its variability was not investigated, we cannot at present rely upon any current platelet test to either initiate, or monitor, or modify or stop treatment with any antiplatelet drug. Evidence is, however, increasing that traditional platelet aggregometry and other more recently developed platelet function assays could be useful to optimize antiplatelet therapy and to predict major adverse cardiac events.The observation of interindividual differences in platelet response to antiplatelet drugs has enlarged the spectrum and the possible clinical relevance of the variability of platelet indices or function. The development of "personalized medicine" will benefit from the concepts discussed in this chapter.
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Affiliation(s)
- Giovanni de Gaetano
- Research Laboratories, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica, Largo Gemelli, 1, 86100, Campobasso, Italy.
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Rank A, Nieuwland R, Roesner S, Nikolajek K, Hiller E, Toth B. Climacteric lowers plasma levels of platelet-derived microparticles: a pilot study in pre- versus postmenopausal women. Acta Haematol 2012; 128:53-9. [PMID: 22627113 DOI: 10.1159/000337327] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2011] [Accepted: 02/08/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet- (PMP) and endothelial cell-derived microparticles (EMP). METHODS In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. RESULTS No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 × 10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 × 10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 × 10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 × 10(6)/l, range 139-462, vs. 121 × 10(6)/l, range 74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 × 10(6)/l, range 182-551, vs. 137 × 10(6)/l, range 64-432; p = 0.015). CONCLUSION Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women.
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Affiliation(s)
- Andreas Rank
- Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands.
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