In vitro characterization of rare anti-α IIb β 3 isoantibodies produced by patients with Glanzmann thrombasthenia that severely block fibrinogen binding and generate procoagulant platelets via complement activation.
Autor: | Lee CSM; ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia., Huguenin Y; Competence Centre for Inherited Bleeding Disorders, University Hospital of Bordeaux, Bordeaux, France., Pillois X; French Reference Centre for Inherited Platelet Disorders, University Hospital of Bordeaux, Pessac, France., Moulieras M; French Reference Centre for Inherited Platelet Disorders, University Hospital of Bordeaux, Pessac, France., Marcy E; French Reference Centre for Inherited Platelet Disorders, University Hospital of Bordeaux, Pessac, France., Whittaker S; ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia., Chen VMY; ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia.; Department of Haematology, Concord Repatriation General Hospital and NSW Health Pathology, Sydney, New South Wales, Australia., Fiore M; French Reference Centre for Inherited Platelet Disorders, University Hospital of Bordeaux, Pessac, France.; Department of Haematology, University Hospital of Bordeaux, Pessac, France.; Inserm U1034, Biology of Cardiovascular Disease, Pessac, France. |
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Jazyk: | angličtina |
Zdroj: | Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2023 Nov 04; Vol. 8 (1), pp. 102253. Date of Electronic Publication: 2023 Nov 04 (Print Publication: 2024). |
DOI: | 10.1016/j.rpth.2023.102253 |
Abstrakt: | Background: Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet α Objectives: In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties. Methods: Twelve patients with GT were evaluated for anti-α Results: Only 2 samples were able to severely block integrin function. We observed that these 2 sera caused a reduction in platelet size similar to that observed when platelets become procoagulant. Mixing healthy donor platelets with patients' sera or purified IgGs led to microvesiculation, phosphatidylserine exposure, and induction of calcium influx. This was associated with an increase in procoagulant platelets. Pore formation and calcium entry were associated with complement activation, leading to the constitution of a membrane attack complex (MAC) with enhanced complement protein C5b-9 formation. This process was inhibited by the complement 5 inhibitor eculizumab and reduced by polyvalent human immunoglobulins. Conclusion: Our data suggest that complement activation induced by rare blocking anti-α (© 2023 The Authors.) |
Databáze: | MEDLINE |
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