Platelet-vessel wall interaction is mediated by von Willebrand factor (VWF), which thereby plays a major role in physiological hemostasis and thrombotic disease. VWF is released as ultralarge multimers from endothelial cells, whereupon it is cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type I repeats-13). The prohemostatic properties of VWF are dependent of its multimeric size; hence, ADAMTS13 activity is an important determinant in platelet-vessel wall interaction. Deficiency of ADAMTS13 in its most classical form in thrombotic thrombocytopenic purpura can lead to severe thrombotic microangiopathy. However, there is a growing variety of diseases in which ADAMTS13 levels have been found to be decreased and in which reduced cleavage of VWF may play a role. Hence, targeting of VWF cleavage by pharmacological modulation of ADAMTS13 levels is an interesting approach in some of these conditions. This review discusses the available evidence for a role of ADAMTS13 in various disease states and the potential therapeutic benefit of restoration of ADAMTS13 levels.
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