Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

Abstract

SummaryThe Harvard TMA Research Collaborative is a multi-institutional registrybased effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93Á0% vs. 47Á5%, P < 0Á0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13Á2-63Á8%, P < 0Á0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0Á98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.

Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score–matched study

“…These cases of TMA comprise a diverse group of conditions, including drug‐associated TMA, transplant‐associated TMA, disseminated intravascular coagulation (DIC), and metastatic cancer, for which data supporting the use of TPE is poor. Despite evidence‐based guidelines recommending against the routine use of TPE for cases of transplant‐ or cancer‐associated TMA, our findings indicate that approximately 20% to 30% of such patients still receive this therapy . Additionally, some have reported that patients with TMA of unclear etiology but without severe ADAMTS13 deficiency appear to benefit from treatment with TPE, while others have shown that these patients can be safely managed without TPE .…”

“…Subsequently, a FRETS‐based assay utilizing the VWF73 substrate was used for all assays performed at both laboratories. Severe deficiency in ADAMTS13 was defined as an activity level of not more than 10% based on previous work indicating that this cutoff provides excellent sensitivity and specificity for idiopathic TTP …”

“…Nevertheless, practice patterns across these hospitals vary substantially with regard to the use of TPE in patients presenting with TMA and an ADAMTS13 activity level of more than 10%. Taking advantage of this “natural experiment,” we have recently shown no difference in 90‐day mortality across treatment sites for TMA patients without severe ADAMTS13 deficiency despite much less frequent use of TPE at one site compared to the others . These findings prompted us to further study the outcomes in this patient population.…”

Atypical Hemolytic Uremic Syndrome: A Brief Review

“…Such disorders include idiopathic TTP (which is confirmed by the finding of completely suppressed ADAMTS-13, is less likely to present with profound renal impairment, 30,31 and is typically more responsive to plasma exchange), STEC-HUS, Drug Induced TMA (which includes cases occurring in the post-transplant setting and often calcineurin-inhibitor related), HIV-related, 32 disseminated intravascular coagulation (which can produce a MAHA pattern but as opposed to classic TMA, also engenders coagulopathy), hypertensive emergencies, malignancy-related TMA, 33,34 cobalamin deficiency, 35-38 pregnancy related conditions such as hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, and others. 39 …”

Thrombotic Microangiopathy Following Chemotherapy with S-1 and Cisplatin in a Patient with Gastric Cancer: A Case Report

“…TMA ranges from typical thrombotic thrombocytopenic purpura (TTP) to localized renal TMA (1,2). This disease is associated with a broad range of conditions, including infection, organ transplantation, autoimmune disease and pregnancy (3). TMA is also a well-described complication of both cancer and its treatment (4).…”