ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura

Abstract

Background: Despite an increase in our understandings of pathogenesis of thrombotic thrombocytopenic purpura (TTP), the approaches for initial diagnosis and management of TTP vary significantly. Objective: The evidence-based guidelines of the International Society on Thrombosis and Haemostasis (ISTH) are intended to support patients, clinicians, and other health care professionals in their decisions about the initial diagnosis and management of acute TTP. Methods: In June 2018, ISTH formed a multidisciplinary panel that included hematologists, an intensive care physician, nephrologist, clinical pathologist, biostatistician, and patient representatives, as well as a methodology team from McMaster University. The panel composition was designed to minimize the potential conflicts of interests. The panel used the Grading of Recommendations Assessment, Development, and Evaluation approach and the Population, Intervention, Comparison, Outcome framework to develop and grade their recommendations. Public comments were sought and incorporated in the final document. Results: The panel agreed on three recommendations covering the initial diagnosis with emphasis on the importance of ADAMTS13 testing (eg, activity, anti-ADAMTS13 IgG or inhibitor) and assessment of the pretest probability of TTP by clinical assessment and/or the risk assessment models like the PLASMIC or French score. The panel noted how availability and turnaround time of ADAMTS13 test results might affect early diagnosis and management, in particular the use of caplacizumab. Conclusions: There is a lack of high-quality evidence to support strong recommendations for the initial diagnosis and management of a suspected TTP. The panel emphasized the importance of obtaining ADAMTS13 testing in a proper clinical context. | 2487 ZHENG Et al.

ISTH guidelines for treatment of thrombotic thrombocytopenic purpura

“…Therefore, caplacizumab use is conditional on the capacity to rapidly identify patients with high likelihood of iTTP (e.g., high clinical suspicion with evidence of severe deficiency of plasma ADAMTS13 activity and presence of inhibitors or anti‐ADAMTS13 IgG). Practically, when treating physicians are considering caplacizumab, they should consider administration of the drug even before the results of plasma ADAMTS13 activity become available (Recommendations 1‐3 in the Guidelines for the Diagnosis of TTP) 1 ; this raises the possibility of overuse in patients who do not actually have the diagnosis of TTP.…”

A multicenter laboratory assessment of a new automated chemiluminescent assay for ADAMTS13 activity

“…In practice, ADAMTS13 levels ≤ 10% (“severe deficiency”) are considered “diagnostic” for TTP 3 . Nevertheless, the 10% cut‐off is relatively arbitrary, and International Society on Thrombosis and Haemostasis (ISTH) guidance identifies results of 10% to 20% as potentially “equivocal.” 11 …”

Should all patients with immune‐mediated thrombotic thrombocytopenic purpura receive caplacizumab?

“…F I G U R E 1 Therapeutic strategy of iTTP, adapted from previous work. 9,19,24 ADAMTS13 activity availability still requires several days in most countries, and a probabilistic approach is usually needed to initiate an optimal therapy immediately. In centers where ADAMTS13 activity is available immediately, the full treatment associating TPE, immunosuppression, and caplacizumab should be started as soon as severe ADAMTS13 deficiency (activity < 10%) is documented.…”