Clinical features and outcomes in patients with thrombotic microangiopathy not associated with severe ADAMTS13 deficiency

Abstract

BACKGROUND The a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity assay has become important in distinguishing autoimmune thrombotic thrombocytopenic purpura from other forms of thrombotic microangiopathy (TMA). Although the significance of severe deficiency in ADAMTS13 (activity levels 10% or less) has been well defined, little data are available on the clinical importance of mild to moderate deficiency (activity levels 11%‐70%) among patients with TMA. STUDY DESIGN AND METHODS We conducted a retrospective study using the Harvard TMA Research Collaborative Registry. Among 254 patients who met the inclusion criteria for TMA, 186 patients with ADAMTS13 activity levels greater than 10% were divided into moderate‐deficiency (11%‐40%), mild‐deficiency (41%‐70%), and no‐deficiency (greater than 70%). RESULTS Compared with mild or no deficiency, moderate ADAMTS13 deficiency correlated with older age; higher bilirubin and international normalized ratio; and increased frequency of sepsis, shock, or multiorgan failure. Platelet counts, lactate dehydrogenase levels, and the presence of renal or neurologic dysfunction did not vary across the three patient cohorts. While moderate ADAMTS13 deficiency was associated with increased 90‐day mortality in univariate analysis, this association was no longer significant in multivariate analysis. Variables that independetly predicted 90‐day mortality in this cohort of patients included Charlson comorbidity index, alanine aminotransferase level, platelet count, creatinine, and the presence of sepsis, shock, or multiorgan failure. CONCLUSION Moderately deficient ADAMTS13 activity identifies a cohort of patients with TMA who are at increased risk for 90‐day mortality. The ADAMTS13 activity level in this group is not an independent predictor of poor outcomes but instead appears to be a marker of disease acuity.

Deficiency of complement factor H-related proteins and autoantibody-positive hemolytic uremic syndrome in an infant with combined partial deficiencies and autoantibodies to complement factor H and ADAMTS13

“…The 3-month-old infant described in this report had a severe episode of acute renal failure in association with both reduced FH antigen levels (∼25% of normal infant levels) and reduced functional ADAMTS13 activity (39%) [ 17 ] ADAMTS13 activity levels in aHUS studies are typically >10%. Patients with <10% plasma ADAMTS13 usually have severe thrombotic thrombocytopenic purpura (TTP), however, ADAMTS13 levels of 11–25% [ 18 ] and 11–70% [ 19 ] have been reported in two large TMA patient studies.…”

Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension

“…On the other hand, there was no relationship between plasma ADAMTS13 and vWF levels in men with myocardial infarction [25]. The LDH levels were not correlated with ADAMTS13 activity in a group of 254 patients with TMA [26]. Moderately reduced ADAMTS13 activity may suggest a thrombotic tendency in hypertensive emergency, which was indicated by higher levels of Fg in patients with MHT.…”

Successful plasma exchange in a 34‐year‐old woman with diabetic ketoacidosis and a thrombotic microangiopathy

“…As reported recently, patients who have TMA with ADAMTS13 activity levels >10% have a range of diagnoses, presentations, outcomes, and responses to TPE . Deciphering the exact role of ADAMTS13 activity and the underlying mechanism of TMA in differing clinical conditions remains to be elucidated.…”

“…TTP can be distinguished from other causes of TMA by a severe deficiency of ADAMTS13 activity, usually below 10% . However, there are other conditions, such as sepsis and autoimmune diseases, that can be associated with a TMA . In these cases, ADAMTS13 activity is decreased, but not deficient, and lies within a “grey zone.” In such cases, TPE may be initiated, but the response is variable and usually unfavorable.…”