Shades of Grey-The brain in TTP.

In their paper, Hannan et al. suggest that new approaches to the management of the acute and remission phases of thrombotic thrombocytopenic purpura should be considered to address white matter changes seen in patients undergoing magnetic resonance imaging. Timely intervention may have significant implications for the long-term physical and mental health of patients. Commentary on: Hannan et al. Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI. Br J Haematol 2024;204:1005-1016.

Real-world use of thrombopoietin receptor agonists for the management of immune thrombocytopenia in adult patients in the United Kingdom: Results from the TRAIT study.

Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA. A platelet count ≥30 × 109/L was achieved in 89% of patients with the first TPO-RA treatments, while 68% achieved a platelet count ≥100 × 109/L. Treatment-free response (TFR; platelet count ≥30 × 109/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO-RAs, most of whom achieved platelet counts ≥30 × 109/L with the second TPO-RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO-RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO-RAs had similar efficacy and safety profiles to those reported in clinical studies.

Practical Considerations for the Use of the Rapid AcuStar® ADAMTS13 Activity Assay in the Diagnosis of Acute Thrombotic Thrombocytopenic Purpura (TTP).

Introduction: Conventional practice in the management of acute TTP entails empirical treatment of suspected cases whilst awaiting confirmatory ADAMTS13 deficiency testing. Rapid ADAMTS13 assays offer increased accessibility and rapid diagnostics. The new automated HemosIL AcuStar® ADAMTS13 assay has seen increasing use among UK TTP Specialist Centres alongside the traditional ELISA method to confirm severe ADAMTS13 deficiency. Methods: A multi-centre retrospective case-control study was performed to review patients demonstrating discrepant ADAMTS13 activity results measured using rapid (AcuStar®) and ELISA assays in parallel from September 2019 to December 2021. Cases were compared with a cohort of suspected TTP patients exhibiting no difference in assay results and in relation to their presenting characteristics and pre-test probability of a diagnosis of TTP. Results: Where the clinical index of suspicion for TTP was high at presentation, acute TTP was confirmed using the AcuStar® assay < 0.2 IU/dL and subsequently < 10 IU/dL by ELISA with zero incidence of discrepancy. For patients with low clinical suspicion of acute TTP, a discrepancy between the AcuStar® and ELISA assay results was observed in 2% of cases; 5-10 IU/dL in AcuStar®, confirmed as >20 IU/dL by ELISA. A concurrent cancer diagnosis or sepsis was observed in 40% of discrepant cases. Conclusions: Where acute TTP is strongly suspected, there is a good correlation between the rapid AcuStar® ADAMTS13 assay and the conventional ELISA assay. Where the clinical suspicion of acute TTP is low, caution should be exercised in the interpretation of the ADAMTS13 activity using the AcuStar® assay. Accurate interpretation requires robust ADAMTS13 testing algorithms to be incorporated into diagnostic pathways.

Caplacizumab in paediatric immune thrombotic thrombocytopenic purpura (iTTP): the UK TTP Registry experience.

Paediatric thrombotic thrombocytopenic purpura (TTP) is an ultra-rare disease. Immune TTP (iTTP) is driven by anti-ADAMTS13 autoantibodies causing an imbalanced VWF:ADAMTS13 axis, and rarer still in children, but potentially life-threatening. Caplacizumab is licensed for iTTP treatment in adults and adolescents aged 12 years and older who weigh 40kg plus. There is a need to clarify whether caplacizumab can be used in younger children. We retrospectively describe caplacizumab use in 16 patients under 18 years of age from the UK TTP Registry, including 4 children aged less than 12 years. For patients weighing less than 40kg (n=3), caplacizumab was dosed at 5mg od. The youngest patient was 33 months old at diagnosis. Plasma exchange (PEX) was used in 15 patients, with a median of 5 exchanges required before platelet count normalisation (range 2-9). One patient was managed without plasma exchange. All patients achieved normalisation of platelet count (median 5.5 days, range 3-28) and ADAMTS13 activity (median 35 days, range 8 to 149), with a median hospital admission of 11 days (range 5 to 26). There were no refractory patients. One patient relapsed at 9 months post presentation. Bleeding requiring VWF supplementation and reduction of caplacizumab use occurred in one patient with severe epistaxis, with no significant intracranial or gastrointestinal bleeding. We demonstrate the efficacy and safety of caplacizumab in the paediatric population, synonymous with the adult trial data: primarily, reduction of PEX compared with the pre-caplacizumab era. This has implications for intensification and duration of admission, particularly relevant in paediatric care.