Treatment and Outcome of Primary and Secondary Thrombotic Microangiopathies

include classical ADAMTS13 deficient acquired (primaryidiopathic) TTP, Shiga toxin-mediated TMA (also called hemolytic-uremic syndrome (HUS)), drug-mediated TMA and complement-mediated TMA (so called atypical HUS). In addition to these, systemic infections, disseminated cancer, severe preeclampsia inc. Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome, malignant hypertension, autoimmune disorders (e.g. systemic lupus erythematosus (SLE), systemic sclerosis (SS), catastrophic antiphospholipid syndrome (CAPS)) and hematopoietic stem-cell (HSCT) or organ transplantations are sometimes associated with TMA. Also, there is a distinct clinical entity resembling TTP occurring after surgical procedures, which is called ‘postoperative TTP’ (pTTP) [6] . In the cohort of Dahlan et al. [4] , nearly half of the patients had no identifiable cause, whereas the other half were found to be with some medical conditions, mainly including infections, drug use, malignancies. Among the cases with secondary TMAs, 10 patients had confirmed HUS secondary to Shiga toxin-producing Escherichia coli O157:H7, of which nine fully recovered with TPE, whereas one died due to brain stem infarction. Drug-induced TMA was identified among 17 patients, and 12 patients had an underlying malignancy (both hematological and solid tumors) [4] . In patients with druginduced TMA, nearly 30% of them died, whereas the remaining 12 survived, of which some fully recovered and some went into remission with renal and neurological sequelae. As expected, the mortality rate among malignancy-associated TMA was as high as 75%. Connective tissue disease (mainly SLE, SS and CAPS) was identified in elevThe first description of thrombotic microangiopathy (TMA), presumably thrombotic thrombocytopenic purpura (TTP), was by Moschcowitz in 1924 [1] . It was a disease presenting with a pentad consisting of anemia, thrombocytopenia, fever, hemiparesis and hematuria, and the postmortem evaluation showed widespread thrombi, mainly composed of platelets, in the terminal circulation of several organs. Although TTP was first characterized by the classical diagnostic pentad, it can present without all of these findings, and the presence of otherwise unexplained microangiopathic hemolytic anemia (MAHA) and thrombocytopenia strongly suggests TTP, which are considered ‘sine qua non’ . Unusually large multimers of von Willebrand factor (vWF) were observed in patients with TTP [2] , which then led to the discovery of a vWF-cleaving proteaseADAMTS13 [3] . ADAMTS13 cleaves vWF multimers that are secreted from vascular endothelial cells, and acquired TTP is an autoimmune disorder caused by inhibitory effects of autoantibodies on ADAMTS13 enzymatic activity. In this issue of American Journal of Nephrology , Dahlan and colleagues shared their experience in 137 patients with primary and secondary TMAs, which were referred to their center for suspected TTP and received therapeutic plasma exchange (TPE) as a first-line treatment for over a decade [4] . The authors displayed the demographic data of the patients as well as the treatment modalities and outcomes. The primary TMA syndromes can be either hereditary (including hereditary TTP (also called Upshaw – Schulman syndrome)) or acquired [5] . Acquired TMA syndromes Published online: July 14, 2015 Nephrology American Journal of