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

Thromb Haemost. 2013 Aug;110(2):316-22. doi: 10.1160/TH13-02-0159. Epub 2013 May 2.

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.

MeSH terms

  • Blood Coagulation / physiology*
  • Blood Platelets / physiology*
  • Factor VIII / antagonists & inhibitors
  • Factor VIII / physiology*
  • Fibrin / biosynthesis*
  • Hemophilia A / blood
  • Hemophilia A / therapy
  • Hemorheology
  • Humans
  • Immobilized Proteins / physiology
  • Perfusion
  • Platelet Adhesiveness
  • Platelet Aggregation
  • Surface Properties
  • Thrombosis / blood
  • Thrombosis / etiology
  • von Willebrand Factor / physiology

Substances

  • Immobilized Proteins
  • von Willebrand Factor
  • Factor VIII
  • Fibrin