ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Vesely SK, George JN, Lammle B, Studt JD, Alberio L, El-Harake MA, Raskob GE. Blood 2003;102(1):60-68.

ABSTRACT:

Initial management of patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic criteria, high mortality without plasma exchange (PE) treatment, and risks of PE. Recent findings suggest that absent or low levels of ADAMTS13 (normally present in plasma) activity may allow the accumulation of ultra-large multimers of von Willebrand factor in plasma. It is hypothesized that these ULVWF cause the intravascular platelet aggregation characteristic of TTP. Although severe ADAMTS13 deficiency may be specific for TTP, the role of ADAMTS13 activity measurements for initial management decisions is unknown. This report describes the role of ADAMTS13 activity measurements in management decisions by describing the relationship of ADAMTS13 activity to presenting features and clinical outcomes in 142 patients with TTP-HUS. ADAMTS13 was measured before beginning PE treatment in 142 (88%) of 161 consecutive patients with clinically diagnosed TTP-HUS with assignment to one of four categories: less than 5% (severe deficiency), 5% to 9%, 10% to 25%, and more than 25%. Eighteen (13%) of 142 patients had severe ADAMTS13 deficiency. Among six predefined clinical categories (stem cell transplantation, pregnant/postpartum, drug association, bloody diarrhea, additional/alternative disorder, idiopathic), severe deficiency occurred only among pregnant/postpartum (2 of 10) and idiopathic (16 of 48) patients. Among those with bloody diarrhea, one (10%) was in the 5-9% category and 9 (90%) were in the more than 25% category measuring ADAMTS13. In addition, 60% of those with bloody diarrhea had severe neurologic abnormalities, 70% had acute renal failure, 80% responded to PE therapy, 40% had a TTP-HUS-associated death, and none relapsed. The presenting features and clinical outcomes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinct from the 32 patients with idiopathic TTP-HUS who did not have severe ADAMTS13 deficiency. Many patients in all ADAMTS13 activity categories apparently responded to PE treatment. Therefore, severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to PE treatment.