Physical mechanisms of platelet formation

Saintillan, David

doi:10.1073/pnas.2014390117

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…Platelet production from megakaryocytes requires a significant amount of energy provided by mitochondria 140 to power DNA endomitosis, microtubule formation, 141 organelle formation and their migration into pro-platelets. 142,143 There have been no precise biophysical measurements of the actual energy production required for these various steps of platelet formation but it is clear that megakaryocyte apoptosis, characterized by decreased mitochondrial activity, 33 is a major cause of the reduced rate of platelet production in ITP.…”

Section: Low-level Laser Lightmentioning

confidence: 99%

Novel therapies for immune thrombocytopenia

Kuter

2021

Br J Haematol

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Summary Current therapies for immune thrombocytopenia (ITP) are successful in providing a haemostatic platelet count in over two‐thirds of patients. Still, some patients have an inadequate response and there is a need for other therapies. A number of novel therapies for ITP are currently being developed based upon the current pathophysiology of ITP. Many therapies are targetted at reducing platelet destruction by decreasing anti‐platelet antibody production by immunosuppression with monoclonal antibodies targetted against CD40, CD38 and the immunoproteasome or physically reducing the anti‐platelet antibody concentration by inhibition of the neonatal Fc receptor. Others target the phagocytic system by inhibiting FcγR function with staphylococcal protein A, hypersialylated IgG, polymeric Fc fragments, or Bruton kinase. With a recognition that platelet destruction is also mediated by complement, inhibitors of C1s are also being tested. Inhibition of platelet desialylation may also play a role. Other novel therapies promote platelet production with new oral thrombopoietin receptor agonists or the use of low‐level laser light to improve mitochondrial activity and prevent megakaryocyte apoptosis. This review will focus on these novel mechanisms for treating ITP and assess the status of treatments currently under development. Successful new treatments for ITP might also provide a pathway to treat other autoimmune disorders.

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Section: Low-level Laser Lightmentioning

confidence: 99%

Novel therapies for immune thrombocytopenia

Kuter

2021

Br J Haematol

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Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes

et al. 2023

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BackgroundPlatelets play a signi cant role in pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and Mean platelet volume (MPV) are the two signi cant parameters that affect functions of the platelets. MethodsIn the current study MPV and PLT count was evaluated using ow cytometry and cell counter. SonoClot analysis was carried out to evaluate Activated Clot Timing (ACT), Clot Rate (CR) and Platelet Function (PF). Genotyping was carried out GSA and Sanger sequencing and expression analysis was carried out using RT-PCR. In silico analysis was carried out using GROMACS tool and UNAFold. The interaction of signi cant proteins with other proteins was predicted using STRING database. Results96 genes were analyzed and a signi cant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated signi cantly with increased MPV, decreased PLT count and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both the genes. In silico analysis revealed that mutation in THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two signi cant proteins interact with many other proteins especially the ones involved in the platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements suggesting that they could be important player in determination of MPV values. ConclusionsIn conclusion the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes and higher MPV can be targeted for better therapeutic outcomes.

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Physical mechanisms of platelet formation

Cited by 2 publications

References 24 publications

Novel therapies for immune thrombocytopenia

Novel therapies for immune thrombocytopenia

Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes

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