Platelet activation and apoptosis induced by pathogenic immune complexes containing platelet factor 4



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Abstract

A severe complication of heparin therapy is heparin-induced thrombocytopenia, which manifests as thrombophilia, including diffuse microthrombosis One of the main triggers of thrombosis are immune complexes formed by antibodies against platelet factor 4 and heparin , followed by massive activation of platelets probably under the influence of these pathogenic immune complexes The mechanisms of platelet impairment by the antigen-antibody complexes are largely unknown. In this work direct effects of the immune complexes formed by recombinant platelet factor 4 and a pathogenic anti-platelet factor 4 monoclonal antibody on isolated human platelets in vitro were investigated. Morphological and biochemical changes in platelets were studied by scanning electron microscopy and flow cytometry It is shown that the pathogenic immune complexes cause platelet activation including formation of pseudopods and platelet aggregation In addition, an increase of phosphatidylserine exposure on the platelet surface and a decrease in mitochondrial membrane potential were observed accompanied by formation of platelet-derived microparticles bearing phosphatidylserine The results indicate that the platelet factor 4-containing pathogenic immune complexes induce platelet activation and apoptosis, which can be an important part of the pathogenesis of thrombocytopenia and microthrombosis complicating heparin administration

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About the authors

T. A Nevzorova

Kazan (Volga region) Federal University

Email: Tatyana.Nevzorova@kpfu.ru

E. R Mordakhanova

Kazan (Volga region) Federal University

I. A Andrianova

Kazan (Volga region) Federal University

R. I Litvinov

Kazan (Volga region) Federal University

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