Predictive Features of Severe Acquired ADAMTS13 Deficiency in Idiopathic Thrombotic Microangiopathies: The French TMA Reference Center Experience

Abstract

Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <30×109/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4–24.2, P<.001), serum creatinine level ≤200 µmol/L (OR 23.4, 95% CI 8.8–62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0–8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

“…The platelet nadir in our cohort is quite close to the mean platelet nadir in ADAMTS 13 activity-deficient patients with thrombotic thrombocytopenia (42), which may lead to diagnostic difficulties.…”

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

“…The rarity of TTP has made registry-based methods an important tool for studying this disease (Vesely et al, 2003;Coppo et al, 2010). These registries have helped address important questions in the diagnosis, management and follow up of TTP patients.…”

“…When any one of these criteria is met in a case of suspected TTP, the sensitivity and specificity to identify cases with severe ADAMTS13 deficiency were 98Á8% and 48Á1%, respectively. When all three criteria were met, sensitivity declined to 46Á9% while specificity increased to 98Á1% (Coppo et al, 2010). This effort highlights the need for a more sophisticated, externally validated, and bedside-deployable clinical risk scoring system to rapidly identify patients with severe ADAMTS13 deficiency who would benefit from prompt treatment with TPE.…”

Egészségügyi szakmai irányelv – A thromboticus thrombocytopeniás purpura (TTP) és a haemolyticus uraemiás syndroma (HUS) kezeléséről

“…A francia munkacsoport adatai alapján az ADAMTS13 deficiens betegek döntő többségének az induló kreatinin értéke <200 mikromol/L [9]. Az akut vesekárosodás (AKI) pontos megítélését ld.…”