Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura

Abstract

Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P < .00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% (Ϸ 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (> 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P < .02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment. (Blood. 2004;103:4043-4049)

Púrpura trombocitopênica trombótica: o papel do fator von Willebrand e da ADAMTS13

“…Peyvandi et al 35 e Zheng et al 36 relataram deficiência grave da atividade da enzima em apenas 48 dos 100 pacientes avaliados. Paradoxalmente, uma deficiência da atividade da ADAMTS13 tem sido relatada em outros casos de microangiopatias trombóticas distintos da PTT.…”

ADAMTS13 activity and inhibitor

“…A typical reference interval is 0.4 inhibitor units. Recent PE therapy may raise ADAMTS13 activity and reduce the inhibitor levels [1,16].…”

“…Patients without severe ADAMTS13 deficiency tended to have TTP secondary to conditions such as bone marrow transplantation and metastatic cancer, and attributed the higher mortality to the underlying disease. Zheng et al analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP [16]. Eight patients with ADAMTS13 activity lower than 5% and no inhibitor at presentation had a complete clinical remission and a rise in ADAMTS13 level after PE.…”

Diagnosis of thrombotic thrombocytopenic purpura with normal ADAMTS13 activity and absence of its inhibitor (anti‐ADAMTS13 antibodies)

“…Although the low levels of ADAMTS13 are typically seen in idiopathic TTP [1], this is not the case for secondary TTP, in particular, drugassociated TTP. Indeed, in most case series, drug-associated TTP does not present with severe deficiency of ADAMTS13 activity levels (defined as <5% activity) or the presence of an ADAMTS13 inhibitor [2][3][4]. Despite the lack of severe ADAMTS13 deficiency in drug-associated TTP, the majority of reported cases show a response to plasma exchange and/or immunosuppressive agents [3,4].…”

“…Indeed, in most case series, drug-associated TTP does not present with severe deficiency of ADAMTS13 activity levels (defined as <5% activity) or the presence of an ADAMTS13 inhibitor [2][3][4]. Despite the lack of severe ADAMTS13 deficiency in drug-associated TTP, the majority of reported cases show a response to plasma exchange and/or immunosuppressive agents [3,4]. To what extent the ADAMTS13 protease contributes to the pathogenesis of secondary/nonidiopathic TTP remains to be defined.…”