Von Willebrand factor and cardiovascular disease. Restricted relevance

Von Willebrand's disease, a bleeding disorder, is caused by deficiencies of an endothelia-derived multimeric glycoprotein receiving the deserved name von Willebrand factor (vWf). Since this factor mediates the interaction between blood platelets and the vessels wall, it was presumed that an increase of its plasma level could be a marker of endothelial lesions and may be also involved in the pathogeny of cardiovascular disease including thrombotic complications. Actually, the unchecked release of ultralarge vWf multimers may cause widespread platelet aggregation into the microcirculation, thereby producing thrombotic thrombocytopenic purpura. More recently, it was demonstrated that such a dramatic condition is normally prevented by the intervention of a protease (ADAMTS-13) which cleaves the ultralarge and large vWf multimers into smaller multimers less active functionally although endowed with antigenic epitopes. The relevance of an immunologic assessment of vWf plasma levels as vWf:Ag should therefore be cautiously considered because this test, more accessible to clinical laboratories, does not provide information about the actual level of large multimers which are functionally active and possibly prothrombotic. It was also reported that an acute phase reaction occurring in various disease states is accompanied by increased plasma vWf levels as the result of endothelial response to adrenergic or proinflammatory stimuli. Clinical and laboratory investigations are highly suggestive that an increased plasma vWf level does not necessarily reflect its leakage from injured endothelia and the laboratory data should be considered in context with the clinical condition and the overall hemostatic balance.