[A new thrombophilia risk factor: the increase of plasma factor VIII].

Factor VIII (FVIII) is key component of the fluid phase of the blood coagulation system. Recent evidence suggests a direct relationship between high plasma levels of FVIII and an increased risk for arterial and venous thrombosis. Thus material reviews the most important clinical and epidemiological evidence about this prothrombotic association. Main function of FVIII is to activate FX functioning as a cofactor for activated FIX in the presence of phospholipids and calcium. Since its deficiency has been historically associated with a hemorrhagic disease (namely hemophilia A), it was never studied its role in thrombosis. In order to explain the association FVIII and thrombosis, defects in its synthesis that increase its plasma concentration as well as postranslational modifications that allow a higher activity, have been proposed. Since 1977 it was suggested that increased plasma concentrations of FVIII and thrombosis may be associated. Shortly after, several other studies confirmed this association. Indeed, patients with stroke of acute myocardial infarction having high plasma levels of FVIII have a shorter survival. On the other hand, deep venous thrombosis is more frequent in patients with high plasma levels of FVIII. This rise in plasma FVIII concentration is also associated with recurrent venous thrombosis. The increment of plasma FVIII concentration is not due to an acute phase reaction. Plasma concentrations of FVIII above 100-150 IU/dL increase 3-fold the risk of thrombosis while concentrations above 150 IU/dL increase the the same risk 6-fold. While it is established the real importance of FVIII as a cause of thrombosis, every patient at risk of thrombosis must have a quantification of this factor. Evaluation of plasma FVIII concentration must be performed in patients with suspected thrombophilia since there is evidence that shows that high plasma FVIII levels is an independent thrombophilic risk factor. There are not effective therapeutic interventions able to normalize the high concentrations of FVIII. Therefore, appropriate prophylaxis during high thrombosis risk clinical episodes is the best alternative for the patient.