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DOI: 10.1160/TH13-02-0159
Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces
Financial support: This study was supported in part by grants (No. 19591129) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to M. Sugimoto), and a grant from the Ministry of Health, Labor and Welfare of Japan for Clinical Research of Myocardial Infarction, Stroke and Diabetes Mellitus (to M. Sugimoto).
Publikationsverlauf
Received:
21. Februar 2013
Accepted after major revision:
16. April 2013
Publikationsdatum:
04. Dezember 2017 (online)
Summary
Coagulation factor VIII (FVIII) plays an essential role in haemostasis. To date, physiologic activity of FVIII circulating in the bloodstream (S-FVIII) is evaluated by classic coagulation assays. However, the functional relevance of FVIII (-von Willebrand factor complex) immobilised on thrombogenic surfaces (I-FVIII) remains unclear. We used an in vitro perfusion chamber system to evaluate the function of I-FVIII in the process of mural thrombus formation under whole blood flow conditions. In perfusion of either control or synthetic haemophilic blood, the intra-thrombus fibrin generation on platelet surfaces significantly increased as a function of I-FVIII, independent of S-FVIII, under high shear rate conditions. This I-FVIII effect was unvarying regardless of anti-FVIII inhibitor levels in synthetic haemophilic blood. Thus, our results illustrate coagulation potentials of immobilised clotting factors, distinct from those in the bloodstream, under physiologic flow conditions and may give a clue for novel therapeutic approaches for haemophilic patients with anti-FVIII inhibitors.
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