VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP

Absent or severely diminished activity of ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) resulting in the intravascular persistence and accumulation of highly thrombogenic ultra large von Willebrand factor (UL-VWF) multimers is the pathophysiological mechanism underlying throm-botic thrombocytopenic purpura. Reduced VWF-cleaving protease lev-els, however, are not uniquely restricted to primary thrombotic micro-angiopathy (TMA), e. g. thrombotic thrombocytopenic purpura, but also occur in other life-threatening thrombocytopenic conditions: se-verely decreased ADAMTS13 activity is seen in severe sepsis, dissemi-nated intravascular coagulation (DIC) and complicated malarial infec-tion. The clinical relevance of these secondary thrombotic microangio-pathies is increasingly recognised, but its therapeutic implications have not yet been determined. The presence of a secondary TMA in certain diseases may define patient groups which possibly could bene