Abstract Number: PB1865
Meeting: ISTH 2020 Congress
Background: Refractory and relapsing thrombotic microangiopathy (TMA) is characterized by increased morbidity and mortality. Physicians are reluctant to use novel efficacious treatments, such as caplacizumab or eculizumab, due to increased cost and lack of validated laboratory testing in many hospitals.
Aims: We evaluated ADAMTS13 activity and complement testing in refractory and relapsing TMA patients.
Methods: We enrolled consecutive TMA patients with samples referred to our Center (01/2018-2020). Severe ADAMTS13 deficiency (< 10%) established thrombotic thrombocytopenic purpura (TTP) diagnosis. ADAMTS13 was also measured in refractory and relapsing patients. If ADAMTS13>10%, complement testing was performed in patients with an indication for complement inhibition. ADAMTS13 activity and the complement marker soluble C5b-9 were measured with commercially available ELISA kits (Technozym and Quidel, respectively). Clinical data were retrospectively collected from referring centers, responsible for treatment decisions.
Results: We studied 80 TMA patients. The majority of patients with relapsing TTP (25/28) had already received rituximab treatment and presented with ADAMTS13< 10% at relapse. During remission, 6/10 patients with available measurements had ADAMTS13< 50% and 2/10 ADAMTS13< 20% , suggesting an imminent relapse.
Patients with secondary TMAs (ADAMTS13>10%) received etiologic treatment, achieving TMA resolution. C5b-9 levels were elevated (median 525 ng/ml, range 313-913 ng/ml) in patients without secondary causes (ADAMTS13>10%); confirming HUS diagnosis. Among HUS, 2 were shiga-toxin associated and resolved with symptomatic treatment in pediatric patients. In atypical HUS, only 1/5 patients received eculizumab and achieved TMA resolution. The other 4 patients succumbed to TMA-related complications. In transplant-associated TMA, 8/16 patients not responding to first-line treatment received eculizumab due to elevated C5b-9 levels (median 253 ng/ml, range 281-1252 ng/ml) and achieved TMA resolution.
Conclusions: Our real-world data confirm that ADAMTS13 and complement testing are valuable tools in relapsing and refractory TMAs, but also highlight the unmet need of using available novel prognostic tools and treatments in clinical practice.
To cite this abstract in AMA style:
Gavriilaki E, Koravou E-, Chatzikonstantinou T, Kalpadaki C, Printza N, Ximeri M, Christoforidou A, Karavalakis G, Tassi I, Tzellou M, Spyridonidis A, Kapsali E, Kollios K, Mandala E, Vlachaki E, Tsirigotis P, Papadaki E, Lalayanni C, Sakellari I, Anagnostopoulos A, Thrombotic Microangiopathy Study Group . Relapsing or Refractory Thrombotic Microangiopathies: The Key Role of ADAMTS13 Activity and Complement Testing [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/relapsing-or-refractory-thrombotic-microangiopathies-the-key-role-of-adamts13-activity-and-complement-testing/. Accessed March 22, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/relapsing-or-refractory-thrombotic-microangiopathies-the-key-role-of-adamts13-activity-and-complement-testing/