Abstract

Severe ADAMTS13 deficiency in thrombotic microangiopathies (TMA) was reported with a variable frequency, which ranges from 13% to 50%. Whether clinical presentation allows to predict accurately severe ADAMTS13 deficiency remains a matter of controversy. To assess this question, we considered all adult (≥ 18 year-old) patients with idiopathic TMA and ADAMTS13 deficiency (< 15% of normal activity) of our Registry, whose clinical characteristics were compared with those of patients with idiopathic TMA and a detectable (≥ 15% normal activity) ADAMTS13 activity. Inclusion criteria were the association of a microangiopathic hemolytic anemia (< 12 g/dL) with a thrombocytopenia (< 150 × 109/L), and no other identifiable cause for cytopenias (transplantation, cancer and chemotherapy, or HIV infection). Patients were included prospectively from October, 2000, to January, 2007, from 17 National centers. One hundred and thirty-five patients were consecutively included. One hundred and two had a severe ADAMTS13 deficiency (58/96 had a plasma inhibitor), and 33 had a detectable ADAMTS13 activity (mean ADAMTS13 activity: 52.7± 29%). Patients with a severe ADAMTS13 deficiency were younger, displayed a lower platelet count and creatinin level, and presented more frequently antinuclear antibodies (ANA) at diagnosis (39.9± 15 versus 49.6± 17.9 year-old, 20± 19.2 versus 56.6± 42.9 × 109/L, 127± 106 versus 425± 335 μmol/L, and 61.8% versus 24.4%, respectively, p<0.001 in all cases). Chronic renal failure occurred more frequently among patients with a detectable ADAMTS13 activity (19.2% versus 1.1%, p<0.001). In a multivariate logistic analysis, patients with severe ADAMTS13 deficiency were more likely to have ANA (Estimated Odds ratio [OR] 4.81, 95% confidence interval [CI] 1.5–15.4), a lower platelet count (OR 0.98, 95% CI 0.96–1), and a lower creatinin level (OR 0.99, 95% CI 0.98–0.99) than patients with detectable ADAMTS13 activity (p< 0.01, 0.14, and < 0.01, respectively). Positive ANA with a platelet count <31 × 109/L and a creatinin level <194 μmol/L represented a set of criteria that allowed to identify patients with a severe ADAMTS13 deficiency with 52% sensitivity, but with a high specificity, at 97%. These criteria had a high positive predictive value for a severe ADAMTS13 deficiency, at 98.2%, and a negative predictive value of 39.5%. ANA, platelet count and creatinin level can predict accurately a severe acquired ADAMTS13 deficiency in idiopathic TMA. This set of criteria may be helpful in the management of patients that require targeted therapies, in association with plasma exchanges.

Author notes

Disclosure: No relevant conflicts of interest to declare.