The significance of ADAMTS13 deficiency in adult
thrombotic microangiopathy (TMA) remains controversial. In an attempt to define the characteristics of adult TMA with severe ADAMTS13 deficiency, we determined 2 groups of patients on the basis of ADAMTS13 activity (undetectable or detectable). Clinical presentation, laboratory values, autoimmune manifestations, and outcome were compared between the groups. Patients were included retrospectively from 12 centers. All fulfilled the diagnosis criteria of TMA. Patients with a history of
transplantation,
cancer and
chemotherapy, and Centers for Disease Control and Prevention (CDC) stage C human immunodeficiency virus (
HIV) infection were not included. Forty-six patients were included. Thirty-one patients had an undetectable ADAMTS13 activity (<5%), and the remaining 15 patients had ADAMTS13 activity of >25%. Severe ADAMTS13 deficiency was associated with a plasmatic inhibitor in 17 cases (55%), suggesting an immune-mediated mechanism. Patients with undetectable ADAMTS13 were more frequently of Afro-Caribbean origin than patients with detectable ADAMTS13 activity (48.4% vs 13.3%, respectively; p = 0.03). As opposed to patients with detectable ADAMTS13 activity, patients with severe ADAMTS13 deficiency displayed various autoimmune manifestations that consisted of nondestructive
polyarthritis (4 cases) associated in 1 case with
malar rash and extramembranous
glomerulonephritis, discoid lupus (3 cases), and autoimmune endocrinopathies,
Raynaud phenomenon, and
sarcoidosis-like disease (1 case each). In patients with severe ADAMTS13 deficiency,
antinuclear antibodies, anti-
double-stranded DNA antibodies, and
anticardiolipin antibodies were positive in 22 (71%) cases, 3 (9.7%) cases, and 1 (3.2%) case, respectively. One patient fulfilled the criteria for the diagnosis of
systemic lupus erythematosus. During follow-up, 1 patient with severe ADAMTS13 deficiency developed
antinuclear antibodies, and 3 others developed anti-
double-stranded DNA antibodies, in association with
neurologic manifestations and
anticardiolipin antibodies in 1 case. Patients with severe ADAMTS13 deficiency also had a lower platelet count (12 x 10(9)/L; range, 2-69 x 10(9)/L) and less severe
renal failure (estimated glomerular filtration rate: 78 mL/min; range, 9-157 mL/min) than patients with detectable ADAMTS13 activity (49.5 x 10(9)/L; range, 6-103 x 10(9)/L; p = 0.0004, and 15.8 mL/min; range, 5.6-80 mL/min; p < 0.0001, respectively).
End-stage renal failure occurred in 1 patient with severe ADAMTS13 deficiency and in 3 patients with detectable ADAMTS13 activity (3.2% vs 21.4%, respectively; p = 0.08). Flare-up and relapse episodes and survival were comparable between the groups. Taken together, these data indicate that adult
idiopathic thrombotic thrombocytopenic purpura, as defined by severe ADAMTS13 deficiency, may occur preferentially in a particular ethnic group, and is characterized by severe
thrombocytopenia, mild renal involvement, and a wide spectrum of autoimmune manifestations that may be completed during follow-up. Indeed, apparently
idiopathic thrombotic thrombocytopenic purpura may be considered a specific
autoimmune disease.