Abstract
Bleeding tendency as a result of clotting factor deficiency is common knowledge. The counterpart, i.e. thrombophilia due to high clotting factor levels, is not surprising, but an association between factor level and thrombosis risk has just recently been described. The role of high factor VIII (FVIII) levels is well documented. The risk of high FVIII levels for the first event is similarly high as that of APC resistance. There is a familiar background of high FVIII levels. Alterations within the FVIII or the von Willebrand factor genes seem to be not causal since polymorphisms of these genes are not associated with venous thromboembolism. An increased FVIII/VWF ratio indicates a reduced FVIII clearance. Probably, the low-density lipoprotein receptor-related protein, i.e. the receptor mediating the hepatic clearance of the FVIII-VWF-complex, is involved. The well known prothrombin G20210A polymorphism is associated with high prothrombin levels perhaps contributing to thrombosis risk via clot resistance against fibrinolysis.
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