thrombopoiesis

Immune thrombocytopenia (ITP) is a disorder characterized by low platelets due to increased clearance and decreased platelet production. While ITP has been characterized as an acquired disorder of the adaptive immune system, the resulting platelet autoantibodies provide ancillary links to the innate immune system via antibody interaction with the complement system. Most autoantibodies in patients with ITP are of the IgG1 subclass, which can be potent activators of the classical complement pathway. Antibody-coated platelets can initiate complement activation via the classical pathway leading to both direct platelet destruction and enhanced clearance of C3b-coated platelets by complement receptors...

Thrombopoiesis is the production of platelets from megakaryocytes in the bone marrow of mammals. In fish, thrombopoiesis involves the formation of thrombocytes without megakaryocyte-like precursors but derived from erythrocyte thrombocyte bi-functional precursor cells. One unique feature of thrombocyte differentiation involves the maturation of young thrombocytes in circulation. In this study, we investigated the role of hox genes in zebrafish thrombopoiesis to model platelet production. We selected hoxa10b, hoxb2a, hoxc5a, hoxd3a, and hoxc11b from thrombocyte RNA expression data, and checked whether they are expressed in young or mature thrombocytes...

BACKGROUND Thromboembolic episodes, which are largely mediated by blood platelets, are prevalent chronic complications of diabetes. The mean platelet volume (MPV) serves as a marker for in vivo platelet activation. This study aimed to assess the factors influencing MPV in 106 patients with type 2 diabetes, compared with 59 non-diabetic individuals at a single center in Poland. MATERIAL AND METHODS We performed linear regression analysis, with MPV as the dependent variable and factors such as age, sex, thrombopoiesis-influencing cytokines, blood pressure, body mass index, glycosylated hemoglobin percentage, platelet count, large platelet count, lipid profile parameters, creatinine concentration, estimated glomerular filtration rate, treatment modalities, and comorbidities as independent variables...

BACKGROUND: Cyclooxygenase (COX)-2 is a rate-limiting enzyme in the biosynthesis of prostanoids, which is mostly inducible by inflammatory cytokines. The participation of COX-2 in the maturation of megakaryocytes has been reported but barely studied in primary immune thrombocytopenia (ITP). METHODS: The expressions of COX-2 and Caspase-1, Caspase-3 and Caspase-3 p17 subunit in platelets from ITP patients and healthy controls (HC), and the expressions of COX-2 and CD41 in bone marrow (BM) of ITP patients were measured and analyzed for correlations...

BACKGROUND: CD34+ cells, megakaryocytes (MKs), and platelets express toll-like receptors (TLRs) that enable these cells to amplify the host innate immune response. However, the role of TLR7/TLR8 activation in megakaryopoiesis has not yet been investigated. OBJECTIVES: We evaluated the effect of coxsackievirus B3 (CVB3) and synthetic TLR7/TLR8 agonists on the development of human MKs and production of platelets. METHODS: CD34+ cells from human umbilical cord were inoculated with CVB3 or stimulated with synthetic TLR7/TLR8 agonists and then cultured in the presence of thrombopoietin...

Abnormal megakaryocyte maturation and platelet production lead to platelet-related diseases and impact the dynamic balance between hemostasis and bleeding. Cellular repressor of E1A-stimulated gene 1 (CREG1) is a glycoprotein that promotes tissue differentiation. However, its role in megakaryocytes remains unclear. In this study, we found that CREG1 protein is expressed in platelets and megakaryocytes and was decreased in the platelets of patients with thrombocytopenia. A cytosine arabinoside-induced thrombocytopenia mouse model was established, and the mRNA and protein expression levels of CREG1 were found to be reduced in megakaryocytes...

BACKGROUND: Immature platelets (IPs) are newly formed platelets released into circulation that have been demonstrated as good markers of thrombopoiesis. Although many flow cytometric and fully automated-based methods are available, the latest Sysmex XN-V hematology analyzer for veterinary use is equipped with a specific fluorescent platelet channel (PLT-F) that detects platelets using a platelet-specific dye. OBJECTIVES: The aims of this study were to evaluate the performance of the Sysmex XSN-1000 V in determining the IPF (immature platelet fraction) and other selected PLT-F channel parameters and to propose IPF reference intervals (RIs) for canine blood samples...

Platelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung are principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number of functional platelets is poor. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates substantial platelet numbers, up to 3000 per megakaryocyte. Despite their large size, megakaryocytes are able repeatedly to passage through the lung vasculature, leading to enucleation and subsequent platelet generation intravascularly...

BACKGROUND: Glucocorticoids are widely known for their immunomodulatory action. Their synthetic analogs are used to treat several autoimmune diseases, including immune thrombocytopenia. However, their efficacy and mechanisms of action in immune thrombocytopenia are not fully understood. OBJECTIVES: To investigate the mechanism of glucocorticoid actions on platelet production. METHODS: The actions of glucocorticoids on platelet production were studied combining in vivo, ex vivo and in vitro approaches...

BACKGROUND: Thrombocytopenia is a common complication in cancer patients undergoing chemotherapy. Chemotherapy-induced thrombocytopenia (CIT) leads to dose reduction and treatment delays, lowering chemotherapy efficacy and survival rate. Thus, rapid recovery and continuous maintenance of platelet count during chemotherapy cycles are crucial in patients with CIT. Thrombopoietin (TPO) and its receptor, myeloid proliferative leukemia (MPL) protein, play a major role in platelet production...

Platelets and their parent cell, the megakaryocyte (MK), are increasingly recognized for their roles during infection and inflammation. The MK residing in the bone marrow or arising from precursors trafficked to other organs for development go on to form platelets through thrombopoiesis. Infection, by direct and indirect mechanisms, can alter the transcriptional profile of MKs. The altered environment, whether mediated by inflammatory cytokines or other signaling mechanisms results in an altered platelet transcriptome...

Megakaryocytes are the main members of the hematopoietic system responsible for regulating vascular homeostasis through their progeny platelets, which are generally known for maintaining hemostasis. Megakaryocytes are characterized as large polyploid cells that reside in the bone marrow but may also circulate in the vasculature. They are generated directly or through a multi-lineage commitment step from the most primitive progenitor or Hematopoietic Stem Cells (HSCs) in a process called "megakaryopoiesis". Immature megakaryocytes enter a complicated development process defined as "thrombopoiesis" that ultimately results in the release of extended protrusions called proplatelets into bone marrow sinusoidal or lung microvessels...

Previous studies have shown that human platelets and megakaryocytes carry microRNAs suggesting their role in platelet function and megakaryocyte development, respectively. However, a comprehensive study on the microRNAs and their targets has not been undertaken. Zebrafish thrombocytes could be used as a model to study their role in megakaryocyte maturation and platelet function because thrombocytes have both megakaryocyte features and platelet properties. In our laboratory, we identified 15 microRNAs in thrombocytes using single-cell RNA sequencing...

Thrombocytopenia is a common haematological problem worldwide. Currently, there are no relatively safe and effective agents for the treatment of thrombocytopenia. To address this challenge, we propose a computational method that enables the discovery of novel drug candidates with haematopoietic activities. Based on different types of molecular representations, three deep learning (DL) algorithms, namely recurrent neural networks (RNNs), deep neural networks (DNNs), and hybrid neural networks (RNNs+DNNs), were used to develop classification models to distinguish between active and inactive compounds...

INTRODUCTION: In diabetic patients, platelets are known to be hyper-reactive with sub threshold stimuli leading to accelerated thrombopoiesis because of their rapid consumption in thrombus formation. HbA1C provides reliable measure of chronic glycemica and correlates with the risk of long term diabetes complications, so that it is currently considered the test of choice for monitoring and management of diabetes mellitus. MATERIALS: 85 consecutive patients on the basis of case selection criteria, presenting to the outpatient and inpatient department of General Medicine were included in the study The purpose of the study and procedures involved were explained to all the patients included in the study in their own language and thereafter an informed consent was taken...

Thrombocytopenia is a major complication in a subset of patients with multiple myeloma (MM). However, little is known about its development and significance during MM. Here, we show thrombocytopenia is linked to poor prognosis in MM. In addition, we identify serine, which is released from MM cells into the bone marrow microenvironment, as a key metabolic factor that suppresses megakaryopoiesis and thrombopoiesis. The impact of excessive serine on thrombocytopenia is mainly mediated through the suppression of megakaryocyte (MK) differentiation...

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, mainly reflected by stage-specific expression of hemoglobin chains. Perinatal alterations of thrombopoiesis remain poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adults. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks) and 10 term neonates, 8 infants (<2a), 5 children (2-13a) and 9 adults (>13a)...

Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance...

The interpretation of the blood count is essential to help the equine clinician in the diagnosis, prognosis, patient management and control of equine diseases. Hematologic alterations often reflect the condition of the individual or an overall response to a pathological situation. A thorough clinical examination of the patient is essential to correctly interpret the hematological results. The most common abnormalities in the erythrogram are mainly anemia and polycythemia. The frequent causes of anemia in horses are acute and chronic blood loss, hemolytic anemia, and anemia caused by chronic disease...

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...