Should we consider caplacizumab as routine treatment for acute thrombotic thrombocytopenic purpura? An expert perspective on the pros and cons.

INTRODUCTION: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disorder. Caplacizumab has been the latest drug incorporated into the initial treatment of acute episodes, allowing for faster platelet recovery and a decrease in refractoriness, exacerbation, thromboembolic events, and mortality. However, caplacizumab is also associated with a bleeding risk and higher treatment costs, which prevent many centers from using it universally. AREAS COVERED: Studies that included iTTP and/or caplacizumab to date were selected for this review using PubMed and MEDLINE platforms. We describe outcomes in the pre-caplacizumab era and after it, highlighting the benefits and risks of its use early in frontline, and also pointing out special situations that require careful management. EXPERT OPINION: It is clear that the availability of caplacizumab has significantly and favorably impacted the management of iTTP patients. Whether this improvement is cost-effective still remains uncertain, and data on long-term sequelae and different healthcare systems will help to clarify this point. In addition, evidence of the bleeding/thrombotic risk of iTTP patients under this drug needs to be better addressed in future studies.

Multicentric evaluation of the new HemosIL Acustar® chemiluminescence ADAMTS13 activity assay.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy (TMA) characterized by the severe deficiency of ADAMTS13 activity (<10%). Rapid ADAMTS13 testing is crucial for early diagnosis and optimal management of TTP patients and other TMAs. The objective of this study was to retrospectively evaluate the performance of the recently commercialized HemosIL Acustar® ADAMTS13 activity chemiluminescent immunoassay (Instrumentation Laboratory, Bedford, Massachusetts, United States) in a multicentric study between Spain and Portugal. METHODS: A comparison method was performed to compare HemosIL Acustar® with an in-house FRETS-VWF73 assay and two commercial ELISA assays: the TECHNOZYM® ADAMTS13 Activity (Technoclone GmbH, Vienna, Austria) and the DG-EIA ADAMTS-13 Activity (Diagnostic Grifols, SA, Barcelona, Spain). A set of 241 frozen plasma samples with known ADAMST13 levels was used. Agreement between methods was assessed with focus on two cut-off ADAMTS13 activity values: <10% (the clinical accepted cut-off value to confirm TTP diagnosis) and <5%. RESULTS: HemosIL AcuStar® showed high agreement with the other methods in correctly classify patients with ADAMTS13 values below 10% (Kappa = 0.89) and even below 5% (Kappa = 0.94) with no false negatives and few false positives (5.40%; 95% CI: 2.20 to 8.60%). However, it also tended to underestimate ADAMTS13 levels, especially for the high assay range values (>40%) (absolute mean bias of 8.40% (95% CI: 6.53 to 10.42%)) when compared to other assays. CONCLUSIONS: HemosIL AcuStar® is highly sensitive to detect ADAMTS13 values below 10% and 5%. A large prospective validation study is needed to corroborate its utility in clinical practice.