Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition associated with severe fetal thrombocytopenia and intracerebral haemorrhage. Antenatal management of subsequent pregnancies relies on intravenous immunoglobulin (IVIg); yet, practice varies internationally and UK data are limited. We conducted a national survey to characterise the current antenatal management of FNAIT across UK regional fetal medicine centres using an electronic, scenario-based design. Responses were analysed descriptively, with ≥75% concordance considered strong agreement. Sixteen of 22 regional fetal medicine centres (73%) responded; all respondents were fetal medicine specialists or haematologists. There was strong consensus to treat standard- and high-risk pregnancies associated with anti-human platelet antigen (HPA)1a or anti-HPA5b antibodies using weekly IVIg, most commonly at a dose of 1 g/kg/week. Earlier initiation of IVIg was favoured for high-risk pregnancies, while timing was more variable for standard-risk cases. Corticosteroids were not routinely used in standard-risk pregnancies but were considered in high-risk scenarios. Fetal blood sampling and intrauterine platelet transfusion were generally avoided. Considerable variation was observed in delivery planning and in the management of pregnancies at risk without a prior confirmed diagnosis. This survey demonstrates the areas of both consistency and variation in UK practice, highlighting gaps in the evidence base and priorities for future research and guidelines development.

Background: Cambridge University Hospitals NHS Foundation Trust provides an adult intestinal/multivisceral transplant service to the United Kingdom. These patients can have complex thrombotic histories and are at risk of bleeding and thrombosis posttransplant. Objectives: We describe our experience of (a) bleeding and thrombosis posttransplant, (b) transplantation for acute abdominal vascular catastrophe, and (c) use of direct oral anticoagulants (DOACs) posttransplant. Methods: A retrospective study of recipients of intestinal transplants at our center between 2007 and June 2023 was conducted. Results: Of 138 recipients (who received 145 grafts), 96 (70%) had a history of thrombosis pretransplant. Of the 145 grafts, 138 (95%) received blood products in the immediate operative period (up to 24 hours postoperatively; day +1) and 6 of 145 (4%) had an intraoperative thrombosis. Major bleeding and thrombosis rates from day +2 to +92 posttransplant were 38.0% (95% CI, 30.0%-46.0%) and 26.1% (95% CI, 19.1%-33.5%), respectively. Bleeds were predominantly gastrointestinal, surgical site, or intra-abdominal. The majority of thromboses (32 of 38 [84%]) were venous (especially catheter associated). No particular relationship between thrombotic and bleeding complications was observed. Eight recipients were transplanted as salvage procedures due to abdominal vascular catastrophe with generally favorable results, although in 3 recipients, no etiology was identified, and anticoagulant failures were seen. Five received DOACs posttransplant, and adequate peak drug levels were seen without bleeding or thrombotic complications. Conclusion: Patients who undergo intestinal transplant are at high risk of bleeding and thrombosis posttransplant. Intestinal transplant was used successfully as a salvage treatment for acute abdominal vascular catastrophe. DOACs were used in selected posttransplant patients. Further multicenter studies are required.

ABSTRACT:Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultrarare thrombotic microangiopathy mediated through inherited deficiency in a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13). To date, >200 ADAMTS13 genetic variants have been associated with cTTP. We report longitudinal follow-up from the UK TTP registry in 104 confirmed cTTP cases (91 consented for follow-up) in a large multiethnic national cohort of patients with cTTP, including a large Black African cTTP cohort. A total of 71 ADAMTS13 variants were identified, with N-terminal variants associated with earlier age at presentation. During the follow-up period (median, 63 months; range, 1-179), 80.2% of patients received regular (plasma derived) prophylaxis, which reduced end organ damage, including stroke/transient ischemic attack (19.0%-1.5%) and renal impairment during follow-up. Postpresentation acute TTP episodes were reduced with prophylaxis (0.68 vs 0.06 acute episodes per follow-up year). Despite regular prophylaxis, symptom control remained apparent on plasma-derived therapy (including headache 42.6%, depression/anxiety 13.2%, fatigue 16.2%, and abdominal pain 13.2%). Most patients with cTTP in the United Kingdom have now switched to recombinant ADAMTS13 (n = 43 [58.9%]), owing to inadequate symptom control (53.5%), plasma reactions (30.2%), or subclinical disease activity (16.3%). This work shows the breadth of ADAMTS13 genetic variants in cTTP and demonstrates efficacy of regular prophylaxis in (1) reducing acute TTP episodes and (2) preventing end organ damage, but despite advances, cTTP related symptoms and the use of blood products remained problematic.

Venous thromboembolism (VTE) remains a leading cause of cardiovascular morbidity and mortality, despite advances in imaging and anticoagulation. VTE arises from diverse and overlapping risk factors, such as inherited thrombophilia, immobility, malignancy, surgery or trauma, pregnancy, hormonal therapy, obesity, chronic medical conditions (e.g., heart failure, inflammatory disease), and advancing age. Clinicians, therefore, face challenges in balancing the benefits of thromboprophylaxis against the bleeding risk. Existing clinical risk scores often exhibit only modest discrimination and calibration across heterogeneous patient populations. Machine learning (ML) has emerged as a promising tool to address these limitations. In imaging, convolutional neural networks and hybrid algorithms can detect VTE on CT pulmonary angiography with areas under the curves (AUCs) of 0.85 to 0.96. In surgical cohorts, gradient-boosting models outperform traditional risk scores, achieving AUCs between 0.70 and 0.80 in predicting postoperative VTE. In cancer-associated venous thrombosis, advanced ML models demonstrate AUCs between 0.68 and 0.82. However, concerns about bias and external validation persist. Bleeding risk prediction models remain challenging in extended anticoagulation settings, often matching conventional models. Predicting recurrent VTE using neural networks showed AUCs of 0.93 to 0.99 in initial studies. However, these lack transparency and prospective validation. Most ML models suffer from limited external validation, "black box" algorithms, and integration hurdles within clinical workflows. Future efforts should focus on standardized reporting (e.g., Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis [TRIPOD]-ML), transparent model interpretation, prospective impact assessments, and seamless incorporation into electronic health records to realize the full potential of ML in VTE.

This practice review addresses the management of haemophilia and heritable bleeding disorders in the ED. These disorders are uncommonly encountered by the emergency physician, but prompt and appropriate management is critical to ensure good outcomes. This practice review describes the principles of emergency care for people with bleeding disorders, with an emphasis on a pragmatic clinical approach, and provides examples of challenging emergencies.

In many patients referred with signi ficant bleeding phenotype, laboratory testing fails to de fine any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses signi ficant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool. Patients with increased bleeding assessment tool scores should progress to hemostasis laboratory testing. To diagnose bleeding disorder of unknown cause (BDUC), normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function, coagulation factors VIII, IX, and XI, and platelet light transmission aggregometry should be the minimum laboratory assessment. In some laboratories, additional specialized hemostasis testing may be performed to identify other rare causes of bleeding. We recommend that patients with a signi ficant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of BDUC in preference to other terminology. Global hemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical signi ficance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for BDUC patients include tranexamic acid, desmopressin, and platelet transfusions.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

Background For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens. Methods This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period. Results Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients. Conclusion This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings.

BACKGROUND:Bleeding disorder of unknown cause (BDUC) is characterized by a bleeding phenotype in the setting of normal hemostatic testing. No standardized diagnostic criteria or treatment algorithms exist for people with BDUC. To address the unmet need, the International Society on Thrombosis and Haemostasis von Willebrand Factor Scientific Subcommittee performed a real-world survey aimed at addressing knowledge gaps, developing consensus pathways, and ultimately improving care. OBJECTIVES:We sought to determine current international clinical practices in the investigation, registration, and treatment of people with BDUC internationally. METHODS:An online structured survey was conducted of healthcare providers who managed patients with bleeding disorders using the ISTH RedCap tool. RESULTS:Two hundred sixteen respondents from 39 countries were included in the final analysis. The clinical assessment of those with a possible bleeding disorder varied, with only 55% excluding hypermobility but high levels (80%) of bleeding assessment tool usage. In hemostatic testing, only the prothrombin time and activated partial thromboplastin time tests gained universal support. Tranexamic acid was favored for prophylaxis for minor (71%)/major (59%) surgeries and pregnancy (58%), but advice on the treatment if bleeding occurred was heterogeneous. The management of heavy menstrual bleeding in women despite combined oral contraceptive pill use also proved challenging, with healthcare providers selecting multiple alternative strategies. CONCLUSION:Significant variation exists in the recognition, registration, and management of people with BDUC worldwide. This survey emphasizes the need for consensus pathways to diagnose and treat BDUC to standardize and improve care for patients internationally.

Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition usually associated with IgG antibody-mediated destruction of the disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) enzyme. In the United Kingdom, acute TTP is treated with plasma exchange (PEX), methylprednisolone, rituximab and caplacizumab.1, 2 Plasma exchange is typically continued until the platelet count is ≥150 × 109/L for two consecutive days, and caplacizumab is continued until ADAMTS13 activity of 30 IU/dL or more on two consecutive occasions after completing plasma exchange.3 A small proportion of patients have a persistent low ADAMTS13 after treatment despite platelet recovery.4 The optimal immunosuppression regimen for these patients is unclear and several strategies have been tried including mycophenolate,5 azathioprine,6 bortezomib7 and more recently daratumumab.8 Van den Berg et al published a case series of two patients with relapsed/refractory TTP,8 both of whom had rapid eradication of the anti-ADAMTS13 IgG antibody titre and normalisation of ADAMTS13 activity within 2 weeks after starting daratumumab. We report the outcomes for the first two patients treated with daratumumab for refractory immune-mediated TTP in the United Kingdom. In case 1, daratumumab was started for refractory TTP because of a persistently undetectable ADAMTS13 activity 105 days after diagnosis. Daratumumab was administered subcutaneously at a standard dose of 1800 mg with 20 mg of oral dexamethasone. Montelukast 10 mg, chlorphenamine 4 mg and paracetamol 1 g were administered to prevent infusion reactions. 20 mg dexamethasone was given for 2 days after daratumumab. The dose of dexamethasone was reduced to 12 mg for the subsequent dose of daratumumab. This patient reached a partial ADAMTS13 response (ADAMTS13 activity 20 IU/dL or greater) after 32 days and was still in partial ADAMTS13 remission at 90 days. The anti-ADAMTS13 IgG antibody titre was 66 IU/mL prior to daratumumab and was undetectable at 90 days (Table 1; Figure 1). Refractory anti-ADAMTS13 IgG antibody Clinical relapse on stopping caplacizumab on day 81. Restarted caplacizumab from day 97 until day 166 Anti-ADAMTS13 IgG antibody titre 66 IU/mL Antigen 54 IU/dL Activity 0 IU/dL Anti-ADAMTS13 IgG antibody titre 129 IU/mL Antigen 53 IU/dL Activity 0 IU/dL In case 2, daratumumab was started for refractory TTP because of a persistently undetectable ADAMTS13 activity 238 days after diagnosis. Daratumumab was given weekly via the intravenous route at 16 mg/kg with dexamethasone 20 mg each time. Chlorphenamine 10 mg and paracetamol 1 g were administered to prevent infusion reactions. The anti-ADAMTS13 IgG antibody titre was 129 IU/mL prior to daratumumab and undetectable at 90 days. ADAMTS13 activity remained undetectable at 90 days. The subcutaneous 1800 mg of daratumumab and weight-based intravenous dosing have been directly compared and have been shown to have equivalent in terms of pharmacokinetics and efficacy in myeloma patients.9 Both patients provided written consent for off-label use of daratumumab. The daratumumab was funded on an individual basis by the hospital trusts. ADAMTS13 activity (TECHNOZYM® ADAMTS13 Activity ELISA Kit), ADAMTS13 antigen (TECHNOZYM® ADAMTS13 Antigen ELISA Kit) and anti-ADAMTS13 IgG antibody titres (TECHNOZYM® ADAMTS13 INH ELISA Kit) were determined by ELISA method. ADAMTS13 activity was typically performed within 24 h of sample collection, whereas ADAMTS13 antigen and anti-ADAMTS13 IgG antibody titres were analysed in batches, delaying incorporation of the results into the clinical management. Remission criteria followed the recommendations of the International Working Group for Thrombotic Thrombocytopenic Purpura consensus report.10 In both cases, the anti-ADAMTS13 IgG antibody improved after the administration of daratumumab and was negative 90 days after daratumumab. In case 1, the patient reached partial ADAMTS13 remission 38 days after two doses of daratumumab. In case 2, the anti-ADAMTS13 IgG antibody was negative by 90 days but this did not correspond with an increase in ADAMTS13 activity. In case 1, there may have been a better response if the patient had completed four doses of daratumumab. In both cases, the anti-ADAMTS13 IgG antibody titre had started falling prior to starting daratumumab and this may represent a delayed effect from the previous immunosuppressant treatments. By contrast to our results, in the Van den Berg case series,8 there was rapid improvement in ADAMTS13 activity within 2 weeks for both the patients they reported. The majority of evidence in treating relapsed/refractory TTP is for anti-CD20 therapy.11, 12 However, in patients who are refractory to these, additional therapies to bring down the anti-ADAMTS13 IgG antibody and restore ADAMTS13 activity are an unmet need. In these patients, if caplacizumab is stopped, they are at risk of clinical relapse, as was demonstrated by case 1. No therapies have clear evidence of efficacy in patients who are refractory to rituximab and oral immunosuppression. While it is an elegant proposal that targeting plasma cells rather than B cells will lead to a rapid clearance of the anti-ADAMTS13 IgG antibody, our results show that this is not the case in all patients. Xie et al.13 have recently published a case series of daratumumab used as part of initial combination treatment. In all three patients, clinical remission was achieved. Given the small numbers, it is unclear whether daratumumab improves the chance of clinical remission after initial treatment. Daratumumab is principally used as a treatment for plasma cell dyscrasias. However, there are case reports of Daratumumab being used to treat patients to remission for autoimmune haematological disorders including immune thrombocytopenia and warm autoimmune haemolytic anaemia.14 In summary, we present the data on the first two patients treated in the UK with daratumumab for refractory immune TTP. Both had a reduction in anti-ADAMTS13 IgG antibody titres after daratumumab and had negative anti-ADAMTS13 IgG antibody titres by 90 days. One patient reached partial ADAMTS13 remission and one had an unchanged ADAMTS13 activity 90 days after treatment. As daratumumab was given after other immunosuppressant therapies and in both cases the anti-ADAMTS13 IgG antibody titres were starting to fall before starting daratumumab, it is possible that they may have confounded the interpretation of response to daratumumab. Further studies are needed to ascertain the role plasma cell-directed therapy may play in the treatment of relapsed/refractory TTP. AA wrote the first draft of the manuscript and performed the analysis with input from WT and MJRD. WT and MJRD conceived the idea for the manuscript. DW performed laboratory analysis. SP, WT and MJRD managed the patients. All authors critically reviewed the manuscript. AA and MJRD had access to the full data set. We would like to thank Peter Baker and Sarah Harper for running the ADAMTS13 assays in Oxford. We would like to thank Ruth Jolley and Viv Garcia for clinical care of the patients in Cambridge. WT—advisory boards for Sanofi and Ablynx. Support to attend educational meetings from Octapharma. Advisory boards and speakers fees from Takeda are all unrelated to this work. MJRD—advisory boards or speakers' fees for Amgen, Pfizer, Portola, Sanofi and Takeda all unrelated to this work. SP—received fees for educational talks and advisory boards from Sanofi and Alexion. The other authors have no conflicts of interest to declare. Dr Desborough and Dr Thomas will consider requests to share anonymised data via email at: [email protected]. Submitted requests will require a protocol detailing hypothesis, aims, analyses and intended tables and figures. Where possible, we will perform the analyses; alternatively, de-identified data and a data dictionary will be supplied for the necessary variables for remote analysis. Any sharing will be subject to a signed data access agreement.

BACKGROUND:Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are because of peribiliary vascular fibrin microthrombi. We sought to determine the prevalence and consequence of occult fibrin within deceased donor livers undergoing normothermic ex situ perfusion (NESLiP) and evaluate a role for fibrinolysis.METHODS:D-dimer concentrations, products of fibrin degradation, were assayed in the perfusate of 163 livers taken after 2 h of NESLiP, including 91 that were transplanted. These were related to posttransplant outcomes. Five different fibrinolytic protocols during NESLiP using alteplase were evaluated, and the transplant outcomes of these alteplase-treated livers were reviewed.RESULTS:Perfusate D-dimer concentrations were lowest in livers recovered using in situ normothermic regional perfusion and highest in alteplase-treated livers. D-dimer release from donation after brain death livers was significantly correlated with the duration of cold ischemia. In non-alteplase-treated livers, Cox proportional hazards regression analysis showed that D-dimer levels were associated with transplant survival ( P  = 0.005). Treatment with alteplase and fresh frozen plasma during NESLiP was associated with significantly more D-dimer release into the perfusate and was not associated with excess bleeding postimplantation; 8 of the 9 treated livers were free of cholangiopathy, whereas the ninth had a proximal duct stricture.CONCLUSIONS:Fibrin is present in many livers during cold storage and is associated with poor posttransplant outcomes. The amount of D-dimer released after fibrinolytic treatment indicates a significant occult fibrin burden and suggests that fibrinolytic therapy during NESLiP may be a promising therapeutic intervention.

Introduction The therapeutic goal in the management of von Willebrand disease (VWD) is to treat or prevent bleeding events by correcting the deficiency of von Willebrand factor (VWF) and coagulation factor VIII (FVIII). Plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento®​/Biostate®​) is indicated in all age groups for prophylaxis and treatment of haemorrhage or surgical bleeding in patients with VWD when desmopressin is ineffective or contraindicated. A systematic literature review was conducted to evaluate the efficacy, safety and consumption of pdVWF/FVIII in the treatment of patients of all ages with mild, moderate and severe inherited VWD.

Disease relapse is recognized as a risk in immune-mediated thrombotic thrombocytopenic purpura (iTTP) after treatment of the acute presenting episode. Identification of patients at risk of relapse and its patterns are yet to be clearly established. We reviewed patients with iTTP having had >3 years of follow-up over 10 years in the United Kingdom to identify patient characteristics for relapse, assess relapse rates and patterns, and response to anti-CD20 therapy in those with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) relapses (ADAMTS13 activity of <20% without thrombocytopenia). We identified 443 patients demonstrating relapse rates of 40% at 5-year follow-up. At 10-year follow-up, no difference in relapse was observed irrespective of whether rituximab was used at acute presentation (P = .39). Black Caribbean ethnicity increased the risk of disease relapse in the British population. There was a distinct population of patients (6%) that relapsed early with subsequent frequent relapses occurring on average within 2 years (average time to relapse in subgroup, 1.7 years). Overall, nearly 60% of relapses described were ADAMTS13 relapses, with subsequent treatment reducing the risk of progression to clinical relapses. We demonstrate that iTTP diagnosed in the latter part of the study period had lower rates of clinical relapses (22.6% vs 11.1%, P = .0004) with the advent of regular monitoring and preemptive rituximab. In ADAMTS13 relapses, 96% responded to anti-CD20 therapy, achieving ADAMTS13 activity of >20%. Anti-CD20 therapy was demonstrated to be an effective long-term treatment regardless of relapse pattern and there was no loss of this treatment response after subsequent treatment episodes.

In the early 2000s, Professor Ingrid Pabinger, working at the Medical University of Vienna and the Vienna General Hospital, noticed that many patients in the hematology clinic referred with an apparent bleeding tendency had no demonstrable laboratory defect on conventional laboratory tests. Subsequently, this was called unclassified bleeding disorder or bleeding of unknown cause; however, recently, the term bleeding disorder of unknown cause (BDUC) has been agreed as a preferred term. BDUC has previously been defined as “a clear bleeding tendency with normal laboratory tests of haemostasis where non-haematological causes of bleeding (eg, scurvy or liver disease) have been excluded” [1,2].

Summary Rituximab, an anti‐CD20 monoclonal antibody, can be used to treat immune thrombotic thrombocytopenic purpura (iTTP) during acute presentation or disease relapse. Undesirable side‐effects include severe hypersensitivity reactions, particularly anaphylaxis and rituximab‐induced serum sickness, with a minority not maintaining a response to treatment. Alternative humanised anti‐CD20 treatments, obinutuzumab and ofatumumab, have been used. A review of the UK TTP Registry showed 15 patients received these drugs over 26 treatment episodes (eight obinutuzumab and 18 ofatumumab). Indications for alternative anti‐CD20 treatment were severe infusion‐related reactions, acute rituximab‐induced serum sickness and a short duration of disease remission. All patients achieved disease remission (ADAMTS13 [A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] activity ≥30 iu/dl) after a median 15 days and 92% of episodes achieved complete remission (≥60 iu/dl). Seven patients required further treatment for disease relapse with a median relapse‐free survival of 17.4 months. All patients continued to respond to re‐treatment with the preceding drug when relapse occurred. There were four adverse events in 26 treatment episodes (15%) – two infections and two infusion reactions. These results suggest that obinutuzumab and ofatumumab may be considered as an alternative option to rituximab in the treatment of iTTP with a comparable safety profile, absence of significant hypersensitivity reactions and sustained normalisation of ADAMTS13.

A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293 units/L and bilirubin of 228 µmol/L, refractory to standard treatment with corticosteroids and rituximab. An emergency splenectomy was performed that slowed haemolysis but did not completely ameliorate it. Eculizumab, a terminal complement pathway inhibitor, was initiated to arrest intravascular haemolysis and showed a favourable response. AIHA is rare but described after the SARS-CoV-2 Pfizer-BioNTech vaccine. This case highlights the rare complication of AIHA, the use of emergency splenectomy for disease control, and the use of eculizumab.