Thrombotic microangiopathy: differential diagnosis, pathophysiology and therapeutic strategies

Several disease states manifest as thrombotic microangiopathies (TMA), most prominently thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). The recent discovery of the von Willebrand factor cleaving protease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif), found to be deficient in TTP, has helped separate these entities. In contrast, HUS is caused by direct endothelial damage by bacterial toxins, while in familial cases inappropriate complement activation through deficient factor H appears to be a major pathogenetic mechanism. Although enormous progress has been made towards understanding these syndromes, the diagnostic tools and therapies used have hardly changed in the last 20 years, with the standard of care remaining plasma exchange in most cases. In this review, we will cover the multiple etiologic factors for TMAs, with the resultant differential diagnoses, as well as provide insight into the latest pathophysiologic findings and possible implications for treatment.