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Levels of procoagulant microparticles expressing phosphatidylserine contribute to bleeding phenotype in patients with inherited thrombocytopenia

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Inherited thrombocytopenia is a heterogeneous group of hereditary disorders with varying bleeding tendencies, not simply related to platelet count. Platelets transform into different subpopulations upon stimulation, including procoagulant platelets and platelet microparticles (PMPs), which are considered critical for haemostasis. We aimed to investigate whether abnormalities in PMP and procoagulant platelet function were associated with the bleeding phenotype of inherited thrombocytopenia patients. We enrolled 53 inherited thrombocytopenia patients. High-throughput sequencing of 36 inherited thrombocytopenia related genes was performed in all patients and enabled a molecular diagnosis in 57%. Bleeding phenotype was evaluated using the ISTH bleeding assessment tool, dividing patients into bleeding (n = 27) vs. nonbleeding (n = 26). Unstimulated and ADP, TRAP or collagen-stimulated PMP and procoagulant platelet functions were analysed by flow cytometry using antibodies against granulophysin (CD63), P-selectin (CD62P), activated GPIIb/IIIa (PAC-1) and a marker for phosphatidylserine expression (lactadherin). Procoagulant platelets were measured in response to collagen stimulation. An in-house healthy reference level was available. Overall, higher levels of activated platelets, PMPs and procoagulant platelets were found in nonbleeding patients compared with the reference level. Nonbleeding patients had higher proportions of phosphatidylserine and PMPs compared with bleeding patients and the reference level, in response to different stimulations. Interestingly, this finding of high proportions of phosphatidylserine and PMPs was limited to PMPs, and not present in procoagulant platelets or platelets. Our findings indicate that nonbleeding inherited thrombocytopenia patients have compensatory mechanisms for improved platelet subpopulation activation and function, and that generation of phosphatidylserine expressing PMPs could be a factor determining bleeding phenotype in inherited thrombocytopenia.

Original languageEnglish
JournalBlood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
Volume32
Issue number7
Pages (from-to)480-490
Number of pages11
ISSN0957-5235
DOIs
Publication statusPublished - 1 Oct 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

    Research areas

  • Adult, Aged, Blood Coagulation, Blood Platelets/cytology, Cell-Derived Microparticles/metabolism, Female, Hemorrhage/blood, Humans, Male, Middle Aged, Phosphatidylserines/blood, Platelet Activation, Thrombocytopenia/blood, Young Adult

ID: 69933362