Affiliations
- Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tübingen, University of Tübingen, Tübingen, Germany; Centre for Clinical Transfusion Medicine, Tübingen.
- Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tübingen, University of Tübingen, Tübingen, Germany.
- Centre for Clinical Transfusion Medicine, Tübingen, Germany.
- Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tübingen, University of Tübingen, Tübingen, Germany; Centre for Clinical Transfusion Medicine, Tübingen, Germany. tamam.bakchoul@med.uni-tuebingen.de.
PMID: 37102605 PMCID: PMC10542843 DOI: 10.3324/haematol.2022.282275
Abstract
Background: Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder triggered by antibodies (Ab) that bind to platelet factor 4-heparin complexes, causing a prothrombotic state. This study explores the formation and role of a novel procoagulant platelet (PLT) subpopulation induced by HIT antibodies.
Methods: HIT patient-derived antibodies were used to study platelet activation and thrombus formation using an ex vivo thrombosis model. The effects of inhibiting platelet Fc-γ-RIIA engagement, P-selectin, and phosphatidylserine (PS) were evaluated.
Results: HIT antibodies induced a procoagulant platelet subpopulation that significantly increased thrombin generation, fibrin formation, and leukocyte recruitment. Targeting PS specifically blocked procoagulant platelet-mediated thrombus formation.
Conclusions: Procoagulant platelets are key mediators in HIT. Targeting PS may offer a therapeutic approach to prevent thromboembolic events in HIT patients.
Keywords
Heparin-induced thrombocytopenia; Platelets; Thrombosis; Phosphatidylserine; Immune-mediated disorder.
