Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria - PubMed (original) (raw)

Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria

Yukinori Kozuma et al. Br J Haematol. 2011 Mar.

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Abstract

Thrombosis in paroxysmal nocturnal haemoglobinuria (PNH) has been suggested to be due to several pathophysiological states: a suppressed fibrinolytic system, increased leucocyte-derived tissue factor, complement (C')-mediated damage to platelets and endothelia, or increased platelet- and endothelium-derived microparticles (MPs). Because haemolytic attack is often accompanied by thrombosis in PNH, we studied the role of C'-induced release of MPs in the thrombogenesis of PNH. C' activation induced procoagulant alteration in PNH red blood cells (RBC), when assessed by thrombin generation in the presence of C'-activated PNH RBC, which was abolished by their subsequent treatment with annexin V. Significant amounts of procoagulant MPs, measured by phosphatidylserine-binding prothrombinase activity, were released from PNH RBC in association with the formation of C5b-9, but not significantly before C5b-8. Generation of procoagulant, annexin V-binding, MPs from C'-activated RBC was studied also by flow cytometry. While phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), induced the release of MPs from normal RBC as well as PNH RBC, C'-induced release of MPs from PNH RBC was Ca(2+) -independent and not associated with the activation of PKC, calpain or caspase. Procoagulant properties of MPs released from PNH RBC could contribute to the thrombogenesis of PNH.

© 2011 Blackwell Publishing Ltd.

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