• C-reactive protein
• Immune thrombocytopenia purpura
• Platelet
• Prognosis

• Adult
• Humans
• C-Reactive Protein
• Prognosis
• Purpura, Thrombocytopenic, Idiopathic/diagnosis
• Retrospective Studies
• Thrombocytopenia

• 82070127 National Natural Science Foundation of China

• immune thrombocytopenia
• pathogenesis
• treatment
• viral hepatitis

• asia
• chronic liver disease
• end-stage liver disease
• leukopenia
• prognosis liver
• southeast asia
• southeastern
• thrombocytopenia
• ultrasonography

• TLRs
• immune response
• inflammatory function
• platelets
• thrombosis
• viral infection

• Immune system
• Neoplasms
• Thromboprophylaxis
• Thrombosis
• Viruses

• 2020.08969.BD Fundação para a Ciência e a Tecnologia

• Qat
• cirrhosis
• liver failure
• liver transplantation

• il-6
• pa-igg
• partial splenic embolization
• splenic infarction rate
• thrombocytopenia
• thrombopoietin

• Embolization, Therapeutic
• Humans
• Immunoglobulin G
• Interleukin-6
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Thrombocytopenia/complications
• Thrombocytopenia/therapy
• Thrombopoietin/therapeutic use

• hepatitis C virus
• immature platelet fraction
• non-alcoholic fatty liver disease
• platelet count
• spleen volume
• thrombopoietin

• Contrast-enhanced ultrasonography
• Portal vein thrombosis (PVT)
• Portosystemic shunts (PS)
• Splenomegaly
• Three-dimensional ultrasound

• Crushed administration
• Decompensated cirrhosis C
• Direct-acting antiviral
• Intractable epilepsy
• Thrombocytopenia

• children
• immune thrombocytopenia
• viral infection

Coronary artery disease (CAD) has been recognized as a serious and potentially life‐threatening complication of Hepatitis C Virus (HCV) infection. High on‐treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. This post hoc analysis aims to assess high on‐treatment platelet reactivity, severity of CAD, and long‐term outcomes of patients with acute coronary syndrome (ACS) who were infected with HCV.

Patients with ACS who were infected with HCV (n=47) were matched to patients with ACS and without HCV (n=137) for age, sex, diabetes mellitus, hypertension, and renal function. HCV‐infected patients with ACS had higher levels of platelet reactivity (ADP₁₀–light transmittance aggregometry, 56±18% versus 44±22% [P=0.002]; arachidonic acid–light transmittance aggregometry, 25±21% versus 16±15% [P=0.011]) and higher rates of high on‐treatment platelet reactivity on clopidogrel and aspirin compared with patients without HCV. Moreover, HCV‐infected patients with ACS had higher rates of multivessel disease (53% versus 30%; P=0.004) and 3‐vessel disease (32% versus 7%; P<0.001) compared with patients without HCV. At long‐term follow‐up, estimated rates of major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, and ischemia‐driven revascularization) were 57% versus 34% (P=0.005) in HCV‐ and non–HCV‐infected patients with ACS, respectively. In addition, thrombolysis In Myocardial Infarction (TIMI) major bleeding rates were higher in HCV‐infected patients (11% versus 3%; P=0.043) compared with noninfected patients. Multivariable analysis demonstrated that HCV infection was an independent predictor of high on‐treatment platelet reactivity, severity of CAD, and long‐term outcome.

In this hypothesis‐generating study, patients with ACS and HCV infection showed increased on‐treatment platelet reactivity, more severe CAD, and worse prognosis compared with patients without HCV.

• acute coronary syndrome
• hepatitis C virus
• high on‐treatment platelet reactivity
• long‐term outcome
• multivessel disease

• Autoantibodies
• Chronic hepatitis
• Hypersplenism
• Thrombocytopenia
• Thrombopoietin

• Biomarkers/blood
• Hepatitis C, Chronic/complications
• Humans
• Liver Cirrhosis/blood
• Liver Cirrhosis/complications
• Liver Cirrhosis/virology
• Male
• Mean Platelet Volume
• Middle Aged
• Platelet Count
• Tissue Plasminogen Activator/physiology

• Dalian Municipal Youth Science and Technology Star

Chronic liver disease (CLD) is a condition that progresses over time toward advanced disease state which is known as liver cirrhosis. Liver cirrhosis leads to dangerous health problems among people living across the world. One such problem that observed in about 75% of cirrhotic patients is thrombocytopenia; which in turn associated with poor prognosis and recovery from CLD. Beyond these, thrombocytopenia in cirrhotic patients led to impairment of coagulation cascade and significantly influenced the utilization of effective mechanism in the management of CLD. By nature, treatment of CLD involves invasive diagnostic and treatment procedures; therefore, in the presence of thrombocytopenia implementing these methods put the lives of patients in a critical health problem due to increased risk of bleeding and mortality. Because of these reasons, prophylactic transfusion of platelets is considered to be one of the most effective options that reduce the risk of bleeding in patients with CLD that required to undergo an invasive procedure. Although platelet transfusion presented with significant advantages in facilitating the invasive procedure in patients with CLD, refractoriness with repeated use and various problems associated with its transfusion limit the continuous utilization of this important option. With these challenges and current advance in the knowledge of thrombopoiesis, the development of relatively safe and alternative drugs that enhance the production of platelets by interacting with thrombopoietin receptor agonists provides a promising option to platelet transfusion. The discovery and approval of romiplostim and eltrombopag in August 2008 and November 2008, respectively, for the treatment of chronic immune thrombocytopenia paved a way and followed by the Food and Drug Administration (FDA) approval of 2 potentially advantageous drugs, lusutrombopag, and avatrombopag, in 2018 for the treatment of thrombocytopenia in patients with CLD that required to undergo elective surgery. Therefore, this review aims to assess pathogenesis of thrombocytopenia and its challenges in the management of liver-related issues and, more importantly, gives emphasis to address the potential use of avatrombopag in the treatment of thrombocytopenia underlying CLD, its pharmacokinetics and pharmacodynamics, as well as its toxicological profiles by presenting the most commonly reported adverse events in various trials.

• Thrombocytopenia
• avatrombopag
• chronic liver disease
• platelets
• thrombopoietin receptor agonists

• direct-acting antivirals
• hepatitis C virus
• platelet-associated immunoglobulin G
• thrombocytopenia

• hepatitis C virus
• nonalcoholic fatty liver disease
• platelet count

• Aged
• Area Under Curve
• Biopsy
• Female
• Fibrosis
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/pathology
• Humans
• Liver Cirrhosis/blood
• Liver Cirrhosis/pathology
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/pathology
• Platelet Count/statistics & numerical data
• Reference Values
• Sensitivity and Specificity
• Severity of Illness Index

• Endocrine
• Extrahepatic manifestations
• Hepatitis C
• Idiopathic thrombocytopenic purpura
• Pulmonary

Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.

• Direct-acting antivirals/therapeutic use
• Hepatitis C, Chronic
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Interferon-alpha/therapeutic use
• Ribavirin/therapeutic use
• Thrombocytopenia/drug therapy
• Thrombocytopenia/virology

• acute myeloid leukemia
• eltrombopag
• hematopoietic stem cell transplantation
• hepatitis C virus
• immune thrombocytopenia
• myelodysplastic syndrome
• severe aplastic anemia

• Animals
• Blood Glucose
• Callithrix/metabolism
• Callithrix/virology
• Female
• Glucagon/blood
• Glucagon-Like Peptide 1/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/metabolism
• Insulin/blood
• Lipid Metabolism
• Liver/metabolism
• Male
• Metabolic Diseases/complications
• Metabolic Diseases/virology

• P51 OD011103 NIH HHS
• P51 OD011133 NIH HHS
• R21 AI101170 NIAID NIH HHS
• National Institute of Allergy and Infectious Diseases (US)

Thrombocytopenia (platelet count <150 × 10⁹/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6 % among non-cirrhotic patients with chronic liver disease to 70 % among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient’s risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

• children
• immune thrombocytopenic purpura
• rotavirus

• cirrhosis
• thrombocytopenia
• thrombopoietin

• partial splenic arterial embolization
• telaprevir-based triple therapy
• thrombocytopenia

• cirrhosis
• eltrombopag
• hepatitis C virus
• interferon
• platelets

• Adult
• Age Factors
• Alanine Transaminase/blood
• Area Under Curve
• Aspartate Aminotransferases/blood
• Biomarkers
• Biopsy
• Blood Platelets/cytology
• China
• Female
• Hepatitis B, Chronic/complications
• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Male
• Middle Aged
• ROC Curve
• Retrospective Studies
• gamma-Glutamyltransferase/blood

• platelets
• receptors
• viruses
• infection
• hemostasis

• Animals
• Blood Platelets/immunology
• Blood Platelets/virology
• Host-Pathogen Interactions
• Humans
• Immunity, Innate
• Virus Attachment
• Virus Diseases/immunology
• Viruses/immunology

• Hepatitis E
• immune-mediated
• thrombocytopaenia
• young male

• Adult
• Emergencies
• Hepatitis E/blood
• Hepatitis E/complications
• Hepatitis E/diagnosis
• Hepatitis E virus/isolation & purification
• Humans
• Jaundice/etiology
• Liver Failure, Acute/blood
• Liver Failure, Acute/complications
• Liver Failure, Acute/diagnosis
• Male
• Pakistan
• Thrombocytopenia/etiology

Hepatitis C is a significant public health problem in Egypt where the highest prevalence (14.7%) of hepatitis C virus (HCV) exists. HCV prevalence is even higher among clinical populations and groups at risk of exposure to infection. Chronic HCV infection is associated with several hematological complications that may necessitate bone marrow (BM) examination. The aim of this study is to estimate HCV prevalence among patients referred for BM examination and to explore hematological and BM findings among HCV positive patients. One hundred adult patients referred for BM examination were included in the study and screened for HCV antibodies. Patients' clinical, hematological, and BM findings were recorded. The seroprevalence of HCV among patients referred for BM examination was 42%. The most common indication for BM examination among HCV positive patients was peripheral cytopenias (88.1%). The most common cytopenia detected was thrombocytopenia (85.7%). The most common diagnosis among HCV positive patients was hypersplenism (52.4%) followed by B-lymphoproliferative disorders (19%) and then immune thrombocytopenic purpura (11.9%). In conclusion, HCV prevalence among patients referred for BM examination is higher than that estimated in the general population. Patients with unexplained peripheral cytopenias should be tested for HCV.

Autoimmune thrombocytopenic purpura is an immunological disorder characterized by increased platelet destruction due to presence of anti-platelet autoantibodies. Hepatitis C virus infection, which is one of the most common chronic viral infections worldwide, may cause secondary chronic immune thrombocytopenic purpura.

We report a case of a 51-year-old Caucasian female with hepatitis C virus infection who developed a severe, reversible, immune thrombocytopenia. Platelet count was as low as 56.000/mm³, hepatitis C virus serology was positive, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and gamma-glutamyltransferase serum levels were elevated. Disorders potentially associated with autoimmune thrombocytopenic purpura were ruled out. A corticosteroid treatment was started and led to an increase in platelet count. The patient was then treated with pegylated-interferon alpha 2a and ribavirin. After four weeks of treatment hepatitis C virus - ribonucleic acid became undetectable and steroid treatment was discontinued. Six months of antiviral therapy achieved a sustained biochemical and virological response together with persistence of normal platelet count.

In our case report hepatitis C virus seemed to play a pathogenic role in autoimmune thrombocytopenic purpura. Moreover, the successful response (negative hepatitis C virus - ribonucleic acid) to tapered steroids and antiviral therapy was useful to revert thrombocytopenia.

A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

• Hepatitis C virus
• Immune disorders
• Cytopenia
• Extrahepatic manifestation
• Autoantibody

• Animals
• Autoimmune Diseases/immunology
• Autoimmune Diseases/virology
• Autoimmunity
• Hepacivirus/immunology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/immunology
• Humans

• HOMA-IR
• hepatitis C virus
• interleukin 28B
• pegylated interferon and ribavirin
• thrombocytopenia

• Aged
• Antiviral Agents/therapeutic use
• Cohort Studies
• Female
• Hemoglobins/analysis
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Humans
• Insulin Resistance
• Interferon alpha-2
• Interferon-alpha/therapeutic use
• Interferons
• Interleukins/genetics
• Male
• Middle Aged
• Platelet Count
• Polyethylene Glycols/therapeutic use
• Pyrophosphatases/genetics
• Recombinant Proteins/therapeutic use
• Ribavirin/therapeutic use
• Thrombocytopenia/diagnosis
• Treatment Outcome
• Viral Load

Eltrombopag is a 2nd generation thrombopoietin-receptor agonist. It binds with the thrombopoietin-receptors found on the surfaces of the megakaryocytes & increases platelet production. Many recent studies have suggested a potential role for this novel agent in the treatment of thrombocytopenia associated with hepatitis-C infection. Studies have shown that adjunct treatment with Eltrombopag can help avoid dose reductions/withdrawals of pegylated interferon secondary to thrombocytopenia. It may also have a role in priming up platelet levels to help initiate antiviral therapy. Similarly, chronic liver disease patients with thrombocytopenia who need to undergo an invasive procedure may be potential candidates for short two-week courses of eltrombopag in the periprocedural period to help reduce the risk of bleeding. Besides the price (deemed very expensive and probably not cost-effective), there are some legitimate concerns about the safety profile of this novel agent (most importantly, portal vein thrombosis, bone marrow fibrosis and hepatotoxicity). In this article, the potential role of eltrombopag in the context of hepatitis C virus (HCV)-related thrombocytopenia is reviewed. To write this article, a MEDLINE search was conducted (1990 to November 2012) using the search terms “eltrombopag,” “HCV,” and “thrombocytopenia.”

• chronic immune thrombocytopenic purpura
• liver disease
• romiplostim
• thrombopoietin-receptor agonist

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients.

A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×10³/μL. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months.

Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ≥50×10³/μL and all non-responders had platelet count <50×10³/μL.

Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection.

• hcv
• peg-ifn-α
• ribavirin
• thrombocytopenia

• Adult
• Antiviral Agents/adverse effects
• Antiviral Agents/therapeutic use
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/drug therapy
• Humans
• Interferon alpha-2
• Interferon-alpha/adverse effects
• Interferon-alpha/therapeutic use
• Male
• Middle Aged
• Multivariate Analysis
• Platelet Count
• Polyethylene Glycols/adverse effects
• Polyethylene Glycols/therapeutic use
• Recombinant Proteins/adverse effects
• Recombinant Proteins/therapeutic use
• Retrospective Studies
• Ribavirin/adverse effects
• Ribavirin/therapeutic use
• Risk Factors
• Severity of Illness Index
• Thrombocytopenia/blood
• Thrombocytopenia/epidemiology

• Adult
• Blood Transfusion/economics
• Blood Transfusion/statistics & numerical data
• Costs and Cost Analysis
• End Stage Liver Disease/complications
• End Stage Liver Disease/economics
• End Stage Liver Disease/physiopathology
• Female
• Health Expenditures/trends
• Health Services/statistics & numerical data
• Humans
• Male
• Middle Aged
• Retrospective Studies
• Thrombocytopenia/economics
• Thrombocytopenia/etiology
• Thrombocytopenia/therapy
• United States

• Blood Platelets/virology
• Hepacivirus/isolation & purification
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/pathology
• Humans
• Male
• Middle Aged
• Purpura, Thrombocytopenic, Idiopathic/blood
• Purpura, Thrombocytopenic, Idiopathic/virology