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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
1   Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan
3   Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
,
Mitsuhiko Sugimoto
1   Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan
,
Hideto Matsui
1   Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan
,
Yasunori Matsunari
1   Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Nara, Japan
2   Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan
,
Midori Shima
3   Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
› Author Affiliations 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).
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Publication History

Received: 21 February 2013

Accepted after major revision: 16 April 2013

Publication Date:
04 December 2017 (online)

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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
 

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