The recent characterization of a von Wille-brand factor cleaving protease, now called ADAMTS13, was a major breakthrough in understanding the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Congenital deficiency of ADAMTS13 causes chronic relapsing TTP, and acquired antibodies that inhibit ADAMTS13 often cause TTP in adults. Nevertheless, the value of ADAMTS13 data for diagnosis or to guide treatment remains uncertain. ADAMTS13 deficiency reportedly is present in almost all patients with “idiopathic” TTP who lack both pre-existing medical conditions and acute renal failure (Tsai and Lian, N Engl J Med. 1998; 339:1585-1594), but the correlation between ADAMTS13 deficiency and thrombotic microangiopathy appears less perfect in less highly selected patient groups (Veyradier et al, Blood. 2001;98:1765-1772). Another unanswered question is whether ADAMTS13 assays can predict the efficacy of plasma exchange therapy.
Vesely and colleagues (page 60) have addressed these points in a prospective study of 142 consecutive patients with thrombotic microangiopathy. Treatment was remarkably uniform, and follow-up was almost complete. The results confirm an association of ADAMTS13 deficiency with idiopathic thrombotic microangiopathy but also show that many such patients have normal ADAMTS13 levels. Futhermore, some patients with ADAMTS13 deficiency had acute renal failure, and apparent responses to plasma exchange therapy occurred at all ADAMTS13 activity levels.
The results for all patients, not just those with idiopathic disease, suggest a potential role for ADAMTS13 assays in identifying patients with an especially poor prognosis. For example, for ADAMTS13 levels of 9% or lower, the death rate was 12%, whereas for ADAMTS13 levels greater than 10%, the death rate was a disappointing 40%. This study represents an important step toward learning when or whether to use ADAMTS13 assays in thrombotic microangiopathy, and the results may help to identify subgroups for whom the role of plasma exchange therapy should be re-evaluated.