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Key Role of Platelet Procoagulant Activity in Tissue Factor‐and Collagen‐Dependent Thrombus Formation in Arterioles and Venules In Vivo Differential Sensitivity to Thrombin Inhibition
Author(s) -
Kuijpers Marijke J.E.,
Munnix Imke C.A.,
Cosemans Judith M.E.M.,
Vlijmen Bart J. Van,
Reutelingsperger Chris P.M.,
Egbrink Mirjam G.A. Oude,
Heemskerk Johan W.M.
Publication year - 2008
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680701653517
Subject(s) - thrombus , tissue factor , platelet , phosphatidylserine , thrombin , platelet activation , chemistry , coagulation , intravital microscopy , microcirculation , microbiology and biotechnology , pathology , medicine , biology , biochemistry , phospholipid , membrane
Objective : Blood coagulation and platelet activation are mutually dependent processes, but contribute differently to venous and arterial thrombosis. We investigated the interplay of these processes in vivo in a mouse model of arteriolar and venular thrombus formation. Methods : Thrombus formation was studied by intravital (fluorescence) microscopy after topical application of FeCl 3 on mouse mesenteric microvessels. Results : Both in arterioles and venules, the thrombus‐forming process relied on tissue factor‐factor VII(a) interaction, collagen exposure, and glycoprotein VI–mediated platelet activation. Arterial thrombus formation was impaired by mild thrombin inhibition or platelet inhibition, while venous thrombosis was only suppressed by strong thrombin inhibition or by mild thrombin inhibition together with platelet inhibition. Phosphatidylserine‐exposing platelets were present in thrombi of both vessel types, as detected with fluorescently labeled annexin A5. Injection of annexin A5 to shield exposed phosphatidylserine abolished thrombus formation in arterioles and venules, while mutant M1234‐annexin A5 was ineffective. Arterial and venous thrombus formations were only slightly affected in mice carrying the factor V Leiden mutation, suggesting insensitivity to factor Va inactivation. Conclusions : In this microvascular model, the formation of both arterial and venous thrombi relies on collagen‐induced platelet activation and tissue factor–induced thrombin generation. Activated, phosphatidylserine‐exposing platelets play a key role in thrombus growth in arterioles and venules.