Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces

Masaaki Doi; Mitsuhiko Sugimoto; Hideto Matsui; Yasunori Matsunari; Midori Shima

doi:10.1160/TH13-02-0159

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(02): 316-322
DOI: 10.1160/TH13-02-0159

Platelets and Blood Cells

Schattauer GmbH

Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces

Masaaki Doi

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

,

Mitsuhiko Sugimoto

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

,

Hideto Matsui

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

,

Yasunori Matsunari

¹Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan

²Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan

,

Midori Shima

³Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan

› Author Affiliations

Abstract

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.

Keywords

Factor VIII - von Willebrand factor - flow - fibrin generation - haemophilia

Full Text

References

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