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Reevaluation of platelet function in chronic immune thrombocytopenia: impacts of platelet size, platelet‐associated anti‐αIIbβ3 antibodies and thrombopoietin receptor agonists
Author(s) -
Nishiura Nobuko,
Kashiwagi Hirokazu,
Akuta Keigo,
Hayashi Satoru,
Kato Hisashi,
Kanakura Yuzuru,
Tomiyama Yoshiaki
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16439
Subject(s) - platelet , thrombopoietin , autoantibody , chemistry , adenosine diphosphate , receptor , antibody , flow cytometry , platelet activation , medicine , immunology , endocrinology , platelet aggregation , biology , haematopoiesis , microbiology and biotechnology , stem cell
Summary Platelet function of immune thrombocytopenia (ITP) has been controversial because of methodological problems associated with low platelet counts. In this study, we evaluated platelet function in 21 patients with chronic ITP (cITP) using the recently developed flow cytometry (FCM)‐based platelet aggregation assay (FCA) along with a PAC1/CD62P assay. Since ITP platelets are larger than controls, whole platelets (whole gating method) and size‐adjusted platelets (size‐adjusted method) were analysed in the PAC1/CD62P via FCM. We found that: (i) aggregation was equivalent [phorbol myristate acetate (PMA) or adenosine diphosphate (ADP)‐induced] or enhanced [protease‐activated receptor 1‐activating peptide (PAR1AP)‐induced] in cITP compared with control by FCA; (ii) PAC1 or CD62P was also equivalent or enhanced in cITP in the whole gating method; and (iii) in sharp contrast, the size‐adjusted method revealed that ADP‐, PAR1AP‐, and collagen synthetic liquid reactive peptide (SRP)‐induced PAC1 and ADP‐induced CD62P were impaired in cITP. These data suggested that an increase in the number of larger‐sized platelets may compensate for the impaired platelet function of cITP, leading to non‐inferiority of overall platelet function in cITP. Furthermore, we revealed that ADP‐induced aggregation was impaired in the patients with thrombopoietin receptor agonists (TPO‐RAs) or platelet‐associated anti‐αIIbβ3 antibodies compared with the control, suggesting that the presence of anti‐αIIbβ3 autoantibodies and/or administration of TPO‐RAs may have a negative impact on platelet function.