The disappearing act of factor VIII

Factor VIII (FVIII) is a plasma protein critical to the haemostatic system. This notion is illustrated by the severe bleeding disorder that is associated with its functional absence, known as haemophilia A. In addition, several epidemiological studies have revealed an association between the presence of elevated levels of FVIII and thrombotic complications. In view of its relation to thrombotic and haemorrhagic disorders, it is not surprising that FVIII has gained wide attention from the research community in the previous decades. This research has led to a better understanding of not only the structural, functional and physiological aspects of this intriguing protein, but also of the pathogenesis of haemostatic defects associated with FVIII. In the present review, focus will be on the interaction between FVIII and surface receptors that are able to capture FVIII. These interactions are of importance for FVIII, as they may affect both function and survival of FVIII.