The course of ADAMTS‐13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine

Abstract

Summary The therapeutic efficacy of plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) is attributed to the restoration in ADAMTS‐13 (a disintegrin and metalloproteinase with thrombospondin motif‐13) activity by substitution of the enzyme and removal of ADAMTS‐13‐neutralizing autoantibodies. We explored this rationale by analysing ADAMTS‐13 activity and corresponding inhibitor levels during PE‐treatment in 27 episodes from 23 adults with TTP. All patients with an initial episode of TTP (n = 14) and nine of 11 patients with a relapse showed severe ADAMTS‐13 deficiency. ADAMTS‐13 inhibitors were detected in 81% of these patients. Twenty‐one patients responded to PE‐therapy and two patients died. For patients with severe ADAMTS‐13 deficiency, 15 patients (71%) showed a PE‐induced recovery in ADAMTS‐13 activity and six patients (29%) had persistent severe ADAMTS‐13 deficiency despite clinical response. Three patients with recurrent TTP demonstrated a permanent increase in inhibitor titre during therapy. Six patients (43%) with an initial episode of TTP displayed a transient increase in inhibitor titre during PE‐therapy, which was associated with deterioration in clinical and haematological symptoms of TTP. Treatment with vincristine induced an immediate increase in platelet count and ADAMTS‐13 activity in seven of eight patients. We conclude that ADAMTS‐13 activity and inhibitor levels, as measured using current methodology, do not solely determine the clinical course of TTP.

Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative

“…By comparison, the fraction of autoimmune TTP with ADAMTS13 activity levels <5% that is reported in the literature varies from 33% to 100% (Furlan et al, 1998;Tsai & Lian, 1998;Veyradier et al, 2001;Vesely et al, 2003;Kremer Hovinga et al, 2004;Matsumoto et al, 2004;Zheng et al, 2004;Bohm et al, 2005;Sadler, 2008). The high sensitivity reported in this study probably reflects the stringency of our clinical definitions and our careful attention to secondary causes of TMA.…”

High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study

“…However, contrasting results have been obtained by the few studies aimed at establishing whether ADAMTS13 testing during the acute episode helps to identify patients' prognosis and can be used to guide their management [17][18][19][20]. On this basis, there is general agreement that all patients in the acute phase have to receive the most effective treatment [21], and we suggest that, at least presently, the best option is represented by concomitant PE and high dose corticosteroids.…”

Management of Concurrent Severe Preeclampsia and Thrombotic Thrombocytopenic Purpura (TTP)

“…According to severe recent studies those kind of TTP associated with severe deficiency of ADAMTS 13 activity less mortality rate than those with detectable ADAMTS 13 [46][47][48][49]. By contrast, Coppo et al [51] reported much high mortality rate in patients with severe ADAMTS 13 deficiency in comparison to those with non-severe deficiency. Higher mortality rate of patients with detectable ADAMTS 13 activity could be related to the lethal fault of their underlying diseases.…”

“…Define the strong relation between inhibitory anti ADAMTS 13 testing and mortality rate. Overall, we come to the conclusion that existence of anti ADAMTS 13 is associated with a worse prognosis [47][48][49][50][51]. Moreover there are some reports of a positive correlation between high inhibitor titers and severity of clinical manifestations, treatment refractoriness and the rate of deaths [48,52,53].…”