Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets

Elena I. Sinauridze; Dmitry A. Kireev; Nadezhda Y. Popenko; Aleksei V. Pichugin; Mikhail A. Panteleev; Olga V. Krymskaya; Fazoil I. Ataullakhanov

doi:10.1160/TH06-06-0313

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2007; 97(03): 425-434
DOI: 10.1160/TH06-06-0313

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets

Authors

Elena I. Sinauridze

¹National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia
Dmitry A. Kireev

¹National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia
Nadezhda Y. Popenko

¹National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia
Aleksei V. Pichugin

²Institute of Immunology, Ministry of Health, Moscow, Russia
Mikhail A. Panteleev

¹National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia
Olga V. Krymskaya

¹National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia
Fazoil I. Ataullakhanov

¹National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia

³Faculty of Physics, Moscow State University, Moscow, Russia

⁴Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia

Abstract

Summary

Platelet microparticles (PMPs) are small vesicles released from blood platelets upon activation. The procoagulant activity of PMPs has been previously mainly characterized by theirability to bind coagulation factors VIII and Va in reconstructed systems. It can be supposed that PMPs can contribute to the development of thrombotic complications in the pathologic states associated with the increase of their blood concentration. In this study we compared procoagulant properties of calcium ionophore A23187-activated platelets and PMPs using several in-vitro models of hemostasis. Surface densities of phosphatidylserine, CD61, CD62P and factor X bound per surface area unit were determined by flow cytometry. They were 2.7-, 8.4-, 4.3-, and 13-fold higher for PMPs than for activated platelets, respectively. Spatial clot growth rate (V_clot) in the reaction-diffus ion experimental model and endogenous thrombin potential (ETP) were determined in plasma, which was depleted of phospholipid cell surfaces by ultra-centrifugation and supplemented with activated platelets or PMPs at different concentrations. Both V_cllot and ETP rapidly increased with the increase of PMP or platelet concentration until saturation was reached. The plateau values of V_clot and ETP for activated platelets and PMPs were similar. In both assays, the procoagulant activity of one PMP was almost equal to that of one activated platelet despite at least two-orders-of-magnitude difference in their surface areas. This suggests that the PMP surface is approximately 50- to 100-fold more procoagulant than the surface of activated platelets.

Keywords

Platelet - PMPs - procoagulant activity - spatial dynamics of coagulation - thrombin generation - factor X - phosphatidylserine - CD-61 - CD-62P

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Referenzen

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