• Anti-cytokine therapy
• Cytokine signaling
• Cytokines
• Growth factors
• Hematopoiesis
• Immunotherapy
• JAK-STAT pathway
• Molecular cloning
• Recombinant cytokines

• Humans
• History, 20th Century
• Cytokines/therapeutic use
• Cytokines/history
• History, 21st Century
• Intercellular Signaling Peptides and Proteins/therapeutic use
• Intercellular Signaling Peptides and Proteins/history
• Animals
• Recombinant Proteins/therapeutic use
• Recombinant Proteins/history

• Cancer therapy-induced thrombocytopenia (CT-IT)
• Platelet (PLT)
• Recombinant human thrombopoietin (rhTPO)
• Thrombopoietin (TPO)
• Thrombopoietin receptor agonist (TPO-RAs)

• Humans
• Thrombocytopenia/drug therapy
• Thrombocytopenia/etiology
• Thrombocytopenia/chemically induced
• Neoplasms/drug therapy
• Neoplasms/complications
• Neoplasms/therapy
• Thrombopoietin/therapeutic use
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Receptors, Thrombopoietin/agonists
• Receptors, Thrombopoietin/metabolism
• Thrombopoiesis/drug effects
• Disease Management
• Animals

• acute lymphoblastic leukemia
• avatrompopag
• chemotherapy-induced thrombocytopenia
• efficacy
• safety

• President Foundation of Nanfang Hospital, Southern Medical University

• Acute/chronic
• Bleeding
• ITP
• Immune thrombocytopenia
• Petechiae

• Humans
• Child
• Purpura, Thrombocytopenic, Idiopathic/therapy
• Purpura, Thrombocytopenic, Idiopathic/diagnosis
• Immunoglobulins, Intravenous/therapeutic use
• Platelet Count

• Activity evaluation
• Fatty acid modification
• Purification
• Thrombopoietin mimetic peptide

• Animals
• Dogs
• Mice
• Peptides/isolation & purification
• Peptides/pharmacology
• Platelet Count
• Thrombocytopenia/drug therapy
• Thymidine Monophosphate/therapeutic use

• Mendelian randomization analysis
• pharmacovigilance
• thromboembolism
• thrombopoietin

• Humans
• Aged
• Thrombocytopenia/diagnosis
• Thrombocytopenia/therapy
• Thrombocytopenia/chemically induced
• Myelodysplastic Syndromes/diagnosis
• Myelodysplastic Syndromes/therapy
• Myelodysplastic Syndromes/complications
• Purpura, Thrombocytopenic, Idiopathic/diagnosis
• Purpura, Thrombocytopenic, Idiopathic/therapy
• Purpura, Thrombocytopenic, Idiopathic/complications

• Cirrhosis
• Liver transplantation
• Perioperative period
• Platelet
• Thrombopoietin pre-treatment

• Adult
• Humans
• Disease Progression
• Hemorrhage/chemically induced
• Hemorrhage/complications
• Hemorrhage/drug therapy
• Hydrazines/adverse effects
• Hydrazines/therapeutic use
• Myelodysplastic Syndromes/complications
• Myelodysplastic Syndromes/drug therapy
• Neoplasm Recurrence, Local/drug therapy
• Quality of Life
• Single-Blind Method
• Thrombocytopenia/complications
• Thrombocytopenia/drug therapy

• cancer supportive care
• chemotherapy-induced thrombocytopenia
• interval-compressed chemotherapy
• romiplostim

• diabetes mellitus
• dogs
• glycosylated hemoglobin
• mean platelet volume
• megakaryopoiesis
• platelet mass
• plateletcrit
• platelets

• hemorrhage
• hemostasis
• innate immunity
• platelet
• thrombosis

• Communication
• Hemorrhage
• Hemostasis
• Hemostatics
• Humans
• Thrombosis/diagnosis
• Thrombosis/therapy

Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct toxicity of drug molecules to platelets or megakaryocytes. Immune-mediated thrombocytopenia, on the other hand, involves the formation of antibodies that react to platelet-specific glycoprotein complexes, as in classic drug-induced immune thrombocytopenia (DITP), or to platelet factor 4, as in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Clinical signs include a rapid drop in platelet count, bleeding or thrombosis. Since the patient's condition can deteriorate rapidly, prompt diagnosis and management are critical. However, the necessary diagnostic tests are only available in specialized laboratories. Therefore, the most demanding step in treatment is to identify the agent responsible for thrombocytopenia, which often proves difficult because many patients are taking multiple medications and have comorbidities that can themselves also cause thrombocytopenia. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of the treatment of non-hematologic malignancies. Many patient-related variables (e.g., age, tumor type, number of prior chemotherapy cycles, amount of bone marrow tumor involvement) determine the extent of CIT. CIT is related to the type and dose of chemotherapy, with regimens containing gemcitabine, platinum, or temozolomide producing it most commonly. Bleeding and the need for platelet transfusions in CIT are rather uncommon except in patients with platelet counts below 25x10⁹/L in whom bleeding rates increase significantly and platelet transfusions are the only treatment. Nonetheless, platelet counts below 70x10⁹/L present a challenge. In patients with such counts, it is important to exclude other causes of thrombocytopenia (medications, infection, thrombotic microangiopathy, post-transfusion purpura, coagulopathy and immune thrombocytopenia). If these are not present, the common approach is to reduce chemotherapy dose intensity or switch to other agents. Unfortunately decreasing relative dose intensity is associated with reduced tumor response and remission rates. Thrombopoietic growth factors (recombinant human thrombopoietin, pegylated human megakaryocyte growth and development factor, romiplostim, eltrombopag, avatrombopag and hetrombopag) improve pretreatment and nadir platelet counts, reduce the need for platelet transfusions, and enable chemotherapy dose intensity to be maintained. National Comprehensive Cancer Network guidelines permit their use but their widespread adoption awaits adequate phase III randomized, placebo-controlled studies demonstrating maintenance of relative dose intensity, reduction of platelet transfusions and bleeding, and possibly improved survival. Their potential appropriate use also depends on consensus by the oncology community as to what constitutes an appropriate pretreatment platelet count as well as identification of patient-related and treatment variables that might predict bleeding.

• immune thrombocytopenia
• pharmacodynamics
• pharmacokinetics
• phase I/II
• romiplostim
• safety

• Chemoembolization
• Cirrhosis
• Hepatocellular carcinoma
• Platelet
• Radiofrequency ablation

• Cancer du sein droit
• Deep inspiration breath hold
• Foie
• Inspiration profonde bloquée
• Liver
• Radiation-induced liver disease
• Radiotherapy
• Radiothérapie
• Right-sided breast cancer
• Toxicity
• Toxicités

• immune thrombocytopenia
• pharmacodynamics
• pharmacokinetics
• structure
• thrombopoietin receptor agonist

• Clinical Trials as Topic
• Humans
• Purpura, Thrombocytopenic, Idiopathic/drug therapy
• Purpura, Thrombocytopenic, Idiopathic/immunology
• Receptors, Fc/chemistry
• Recombinant Fusion Proteins/chemistry
• Recombinant Fusion Proteins/pharmacokinetics
• Thrombopoietin/chemistry
• Thrombopoietin/pharmacokinetics

• P30 CA008748 NCI NIH HHS

• HIV
• SARS-CoV-2
• aggregation
• coronavirus
• hantavirus
• influenza
• thrombocytopathy
• thrombocytopenia
• virus infection

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.

Platelets derive from megakaryocytes, which differentiate from hematopoietic stem/progenitor cells (HSPCs). Here, Qu et al show that platelet-derived microparticles carrying miR-1915-3p target HSPCs and promote megakaryopoiesis by suppressing RHOB expression levels.

As do many other immunity-related blood cells, platelets release antimicrobial peptides that kill bacteria, fungi, and even certain viruses. Here we review the literature suggesting that there is a similarity between the antimicrobials released by other blood cells and the amyloid-related Aβ peptide released by platelets. Analyzing the literature, we also propose that platelet-generated Aβ amyloidosis may be more common than currently recognized. This systemic Aβ from a platelet source may participate in various forms of amyloidosis in pathologies ranging from brain cancer, glaucoma, skin Aβ accumulation, and preeclampsia to Alzheimer’s disease and late-stage Parkinson’s disease. We also discuss the advantages and disadvantages of specific animal models for studying platelet-related Aβ. This field is undergoing rapid change, as it evaluates competing ideas in the light of new experimental observations. We summarized both in order to clarify the role of platelet-generated Aβ peptides in amyloidosis-related health disorders, which may be helpful to researchers interested in this growing area of investigation.

• Alzheimer’s disease
• amyloid-beta
• animal models
• natural antibiotics
• platelets

• Immune thrombocytopenia
• antibodies
• aplastic anemia
• eltrombopag
• megakaryocytes
• thrombocytopenia

• eltrombopag
• immune thrombocytopenia
• itp
• platelets
• romiplostim
• thrombopoietin
• thrombopoietin receptor agonists

• Intravital imaging
• megakaryocytes
• thrombopoiesis
• two-photon microscopy

Antibodies to first‐generation recombinant thrombopoietin (TPO) neutralized endogenous TPO and caused thrombocytopenia in some healthy subjects and chemotherapy patients. The second‐generation TPO receptor agonist romiplostim, having no sequence homology to TPO, was developed to avoid immunogenicity. This analysis examined development of binding and neutralising antibodies to romiplostim or TPO among adults with immune thrombocytopenia (ITP) in 13 clinical trials and a global postmarketing registry. 60/961 (6·2%) patients from clinical trials developed anti‐romiplostim‐binding antibodies post‐baseline. The first positive binding antibody was detected 14 weeks (median) after starting romiplostim, at median romiplostim dose of 2 µg/kg and median platelet count of 29.5 × 10⁹/l; most subjects had ≥98·5% of platelet assessments showing response. Neutralising antibodies to romiplostim developed in 0·4% of patients, but were unrelated to romiplostim dose and did not affect platelet count. Thirty‐three patients (3·4%) developed anti‐TPO‐binding antibodies; none developed anti‐TPO‐neutralising antibodies. In the global postmarketing registry, 9/184 (4·9%) patients with spontaneously submitted samples had binding antibodies. One patient with loss of response had anti‐romiplostim‐neutralising antibodies (negative at follow‐up). Collectively, anti‐romiplostim‐binding antibodies developed infrequently. In the few patients who developed neutralising antibodies to romiplostim, there was no cross‐reactivity with TPO and no associated loss of platelet response.

• TPO receptor agonist
• immune thrombocytopenia
• immunogenicity
• romiplostim
• thrombopoietin

5-Fluorouracil (5-FU) is an antimetabolite chemotherapy widely used for the treatment of various cancers. However, many cancer patients experience hematological side effects following 5-FU treatment. Here, we investigated the protective effects of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a mitigator against 5-FU-induced hematologic toxicity, including neutropenia, monocytopenia, thrombocytopenia, and thrombocytosis, in Balb/c mice injected with 5-FU (100 mg/kg, i.p.). Administration of PLAG significantly and dose-dependently reduced the duration of neutropenia and improved the nadirs of absolute neutrophil counts (ANCs). Moreover, while the ANCs of all mice in the control fell to the severely neutropenic range, none of the mice in the PLAG 200 and 400 mg/kg-treated groups experienced severe neutropenia. Administration of PLAG significantly delayed the mean first day of monocytopenia and reduced the duration of monocytopenia. PLAG also effectively reduced extreme changes in platelet counts induced by 5-FU treatment, thus preventing 5-FU-induced thrombocytopenia and thrombocytosis. PLAG significantly decreased plasma levels of the chemokine (C–X–C motif) ligand 1 (CXCL1), CXCL2, interleukin (IL)-6, and C-reactive protein (CRP), which were elevated consistently with the occurrence time of neutropenia, monocytopenia, and thrombocytopenia. When compared with olive oil and palmitic linoleic hydroxyl glycerol (PLH), only PLAG effectively mitigated 5-FU-induced hematological toxicity, indicating that it has a distinctive mechanism of action. In conclusion, PLAG may have therapeutic potential as a mitigator for 5-FU-induced neutropenia and other hematological disorders.

• 5-Fluorouracil
• PLAG
• chemotherapy-induced hematological toxicity
• monocytopenia
• neutropenia
• thrombocytopenia
• thrombocytosis

• beta-amyloid peptide
• alzheimer’s
• glaucoma
• platelets

• Alzheimer Disease/blood
• Alzheimer Disease/etiology
• Amyloid beta-Peptides/metabolism
• Amyloid beta-Protein Precursor/metabolism
• Blood Platelets/metabolism
• Glaucoma/blood
• Glaucoma/etiology
• Humans

• SC1 GM122691 NIGMS NIH HHS
• SC2 GM111149 NIGMS NIH HHS
• SC1GM122691 NIH HHS
• SC2GM111149 NIH HHS

• Adolescent
• Blood Platelets/pathology
• Case-Control Studies
• Child
• Diabetes Mellitus, Type 1/blood
• Female
• Humans
• Male
• Mean Platelet Volume
• Platelet Count
• Sensitivity and Specificity

• Clinical trials
• hemostaseology and platelets
• rituximab
• thrombocytes

• Liver regeneration
• intra-platelet growth factors
• liver resection
• liver transplantation
• platelet transfusion
• platelets
• thrombopoietin analogue

• Adolescent
• Adult
• Age Factors
• Child
• Child, Preschool
• Humans
• Infant
• Practice Guidelines as Topic
• Purpura, Thrombocytopenic, Idiopathic/blood
• Purpura, Thrombocytopenic, Idiopathic/diagnosis
• Purpura, Thrombocytopenic, Idiopathic/pathology
• Purpura, Thrombocytopenic, Idiopathic/therapy

• Adult
• Benzoates/therapeutic use
• Deamino Arginine Vasopressin/therapeutic use
• Hemostatics/therapeutic use
• Humans
• Hydrazines/therapeutic use
• Plasma
• Platelet Transfusion/methods
• Postoperative Care/methods
• Postoperative Hemorrhage/prevention & control
• Pyrazoles/therapeutic use
• Randomized Controlled Trials as Topic
• Receptors, Fc/therapeutic use
• Recombinant Fusion Proteins/therapeutic use
• Thrombocytopenia/complications
• Thrombocytopenia/therapy
• Thrombopoietin/therapeutic use

• 13/89/09 Department of Health

The appearance in the mouth of haemorrhagic petechiae, ecchymoses or blood blisters with spontaneous bleeding is suggestive of a haemorrhagic disorder that may be caused either by functional impairment of platelets or of blood vessel walls, by an abnormal decrease in the number of circulating platelets (thrombocytopaenia), or by defects in the blood clotting mechanism. Thrombocytopaenia from decreased production or increased destruction of platelets may be caused by multiple factors including immune mediated mechanisms, drugs or infections.

A diagnosis of thrombocytopaenic purpura can be made when any other disease entity that might be causing the purpura is excluded on the basis of the medical history, the physical examination, a complete blood count and a peripheral blood smear.

In this paper, we outline the clinical features of oral thrombocytopaenic purpura and briefly discuss some aspects of its aetiopathogenesis and treatment.

• Ecchymosis
• Haemorrhagic blister
• Immune mediated thrombocytopaenia
• Petechiae

Aminoacyl-tRNA synthetases (aaRSs) catalyze aminoacylation of tRNAs in the first step of protein synthesis in the cytoplasm. However, in higher eukaryotes, they acquired additional functions beyond translation. In the present study, we show that an activated form of tyrosyl-tRNA synthetase (YRS^ACT) functions to enhance megakaryopoiesis and platelet production in vitro and in vivo. These findings were confirmed with human megakaryocytes differentiated from peripheral blood CD34⁺ hematopoietic stem cells and with human induced pluripotent stem (iPS) cells. The activity of YRS^ACT is independent of thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from iPS cell-derived hematopoietic stem cells from a patient deficient in TPO signaling. These findings demonstrate a previously unrecognized function of an aaRS which may have implications for therapeutic interventions.

New mechanisms behind blood cell formation continue to be uncovered, with therapeutic approaches for hematological diseases being of great interest. Here we report an enzyme in protein synthesis, known for cell-based activities beyond translation, is a factor inducing megakaryocyte-biased hematopoiesis, most likely under stress conditions. We show an activated form of tyrosyl-tRNA synthetase (YRS^ACT), prepared either by rationally designed mutagenesis or alternative splicing, induces expansion of a previously unrecognized high-ploidy Sca-1⁺ megakaryocyte population capable of accelerating platelet replenishment after depletion. Moreover, YRS^ACT targets monocytic cells to induce secretion of transacting cytokines that enhance megakaryocyte expansion stimulating the Toll-like receptor/MyD88 pathway. Platelet replenishment by YRS^ACT is independent of thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from induced pluripotent stem cell-derived hematopoietic stem cells from a patient deficient in TPO signaling. We suggest megakaryocyte-biased hematopoiesis induced by YRS^ACT offers new approaches for treating thrombocytopenia, boosting yields from cell-culture production of platelet concentrates for transfusion, and bridging therapy for hematopoietic stem cell transplantation.

• megakaryopoiesis
• thrombocytopenia
• tyrosyl-tRNA synthetase

• Immune thrombocytopenia
• c-Mpl
• chronic
• thrombopoietin

• Case-control
• Platelet count
• Platelet turnover
• Platelet volume
• Type 1 diabetes
• Type 2 diabetes

• Adult
• Biomarkers/blood
• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Blood Platelets/metabolism
• Diabetes Mellitus, Type 1/blood
• Diabetes Mellitus, Type 1/diagnosis
• Diabetes Mellitus, Type 1/drug therapy
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/diagnosis
• Diabetes Mellitus, Type 2/drug therapy
• Female
• Glycated Hemoglobin/metabolism
• Humans
• Hypoglycemic Agents/therapeutic use
• Kinetics
• Male
• Mean Platelet Volume
• Middle Aged
• Platelet Count
• Retrospective Studies

Corticosteroids such as prednisolone and dexamethasone have been established as up-front therapy for the treatment of newly diagnosed immune thrombocytopenia. Recent studies have indicated that other treatments such as rituximab or thrombopoietin receptor agonist can also be effective choices. We performed a systematic review and network meta-analysis to establish a clinically meaningful hierarchy of efficacy and safety of treatments for newly diagnosed primary immune thrombocytopenia in adults. Randomized controlled trials evaluating medical treatments for newly diagnosed immune thrombocytopenia were included. Reviewers independently extracted data and assessed the risk of bias. The main outcome was the sustained response (platelet count >30×10⁹/L for 3–6 months after completion of treatments), while overall response (platelet count >30×10⁹/L for 2–4 weeks after initiation of the up-front treatment) and therapy-related adverse events were the secondary endpoints. A total of 21 randomized controlled trials (1898 patients) were included in this study. Our main findings were a significantly better sustained response in the recombinant human thrombopoietin+dexamethasone and rituximab+dexamethasone arms compared to those of conventional therapies (prednisolone and dexamethasone monotherapy). Moreover, recombinant human thrombopoietin+dexamethasone and +prednisolone improved early overall response compared to prednisolone, dexamethasone, and rituximab-containing regimens. Therapy-related adverse events showed similar profiles and were tolerable in all treatment arms. Regimens containing recombinant human thrombopoietin agonist may be beneficial up-front therapies in addition to the conventional corticosteroid monotherapies. Future head-to-head trials including these regimens and rituximab-containing treatments are necessary in order to overcome the limitations of the small number in our study and determine the most suitable initial therapies for newly diagnosed immune thrombocytopenia.

• 13/89/09 Department of Health
• 16895 Cancer Research UK
• SRP/13/89/09 Department of Health

• (Trans-)Differentiation
• Bioreactor
• Drug carrier
• In vitro thrombopoiesis
• Platelet transfusion

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

• Benzoates/therapeutic use
• Bone Marrow Diseases/complications
• Chronic Disease
• Deamino Arginine Vasopressin/therapeutic use
• Hemorrhage/etiology
• Hemorrhage/prevention & control
• Hemostatics/therapeutic use
• Humans
• Hydrazines/therapeutic use
• Platelet Transfusion
• Pyrazoles/therapeutic use
• Randomized Controlled Trials as Topic
• Receptors, Fc/therapeutic use
• Recombinant Fusion Proteins/therapeutic use
• Thrombocytopenia/complications
• Thrombopoietin/therapeutic use
• Tranexamic Acid/therapeutic use