title: Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces.
abstract: 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.
authors: Department of Regulatory Medicine for Thrombosis, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan. sugi-ped@naramed-u.ac.jp
authors: Masaaki
authors: M
authors: Doi
authors: Mitsuhiko
authors: M
authors: Sugimoto
authors: Hideto
authors: H
authors: Matsui
authors: Yasunori
authors: Y
authors: Matsunari
authors: Midori
authors: M
authors: Shima
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000502:physiology*; D005337:Fibrin / Q000096:biosynthesis*; D006467:Hemophilia A / Q000097:blood / Q000628:therapy; D018056:Hemorheology; D006801:Humans; D055767:Immobilized Proteins / Q000502:physiology; D010477:Perfusion; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D013499:Surface Properties; D013927:Thrombosis / Q000097:blood / Q000209:etiology; D014841:von Willebrand Factor / Q000502:physiology
chemical_list: D055767:Immobilized Proteins; D014841:von Willebrand Factor; D005169:Factor VIII; D005337:Fibrin