Real-world data on emicizumab use and monitoring in paediatric severe haemophilia A (HA) patients are scarce. We therefore sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks. Emicizumab levels, activated partial thromboplastin time (aPTT) values, and thrombin generation were measured before and during therapy. Twenty patients experienced zero bleeds. All bleeding was trauma-related, and bleeding risk was positively correlated with the length of emicizumab prophylaxis. Sixteen surgical interventions were performed in 12 patients, with no thrombotic complications or thrombotic microangiopathy. Prolonged aPTT values normalised after emicizumab initiation, correlating with an increase in emicizumab plasma levels. Elevation in the thrombin generation was observed following emicizumab prophylaxis, with lower values recorded in younger infants. Emicizumab prophylaxis was safe and well tolerated. As all bleedings were trauma-related, laboratory monitoring could not predict bleeding risk. Our results do not support routine thrombin generation monitoring in children treated by emicizumab, yet further studies are warranted in the context of surgical procedures.

Introduction Real‐world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce. Aim To study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort. Methods HA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled. Bleeding, adverse events and surgeries were documented. FVIII inhibitors, emicizumab levels and thrombin generation (TG) were sequentially measured. Results A total of 107 patients, including 58 children (whose median (IQR) age was 6 (1–11) years) with severe HA, composed the study cohort. Twenty‐nine per cent (31/107) of our HA patients had FVIII inhibitors. Patients were followed for a median of 67 weeks (up to 144 weeks). Fifty‐three patients, whose median follow‐up was 53 weeks, experienced zero bleeds. Most bleeds (94%) among children were trauma‐related, whereas 61% of adults sustained spontaneous joint bleeds. Four patients experienced major bleeds, with a fatal outcome in one infant, who also presented with central venous line thrombosis. No other serious adverse events were encountered. Seven patients have decided to stop emicizumab treatment for various reasons. Emicizumab plasma levels increased after emicizumab prophylaxis initiation, and values were maintained during follow‐up, in all but one patient, suspected of anti‐drug antibodies. A significant reduction of FVIII inhibitor levels was noted among inhibitor patients. TG was increased and sustained yet could not prognosticate bleeding risk. Conclusion Emicizumab prophylaxis was mostly well tolerated, although 50% of patients experienced breakthrough bleeds. Routine TG monitoring is not obligatory, and further studies are warranted in selected patient populations.

Introduction: Emicizumab (Hemlibra™) is approved for prophylaxis of Haemophilia A (HA) patients with and without inhibitors. However, real-world data on emicizumab use in the elderly HA patients with concomitant cardiovascular risk factors are lacking. Aim: To evaluate the safety and efficacy of emicizumab in a real-world cohort of elderly HA patients. Methods: A prospective longitudinal observational study on HA patients over 50 years old treated, followed and monitored during emicizumab prophylaxis was conducted. We documented any bleeding or adverse events and collected plasma samples for emicizumab levels, aPTT and thrombin generation (TG). Results: Seventeen HA patients (2 with inhibitor), whose median age was 62.4 years (range: 51.5-77.1) composed the cohort, including 9/17 with multiple cardiovascular risk factors (high risk group). Seven patients had chronic HIV infection. The median follow-up of our cohort was 400 days (range 89-805, IQR 211-479 days). The median annualized bleeding rate (ABR) significantly decreased for all patients. Among patients who displayed significant bleeding tendencies, emicizumab steady state levels as well as TG were lower as compared with the group. The ABR of four patients concomitantly treated by antiplatelet agents was significantly higher compared with the rest of the cohort. Neither thrombosis nor thrombotic microangiopathy (TMA) was encountered. Conclusions: Emicizumab prophylaxis for HA patients older than 50 years including those with cardiovascular risk factors was well tolerated. As lower emicizumab and TG levels were observed among bleeding patients, we suggest that monitoring laboratory assays could be of value within this age group.

Bolus injection (BI) of sucrose-formulated recombinant factor VIII (rFVIII-FS) is an approved treatment for haemophilia patients undergoing major surgery. Continuous infusion (CI) during surgery has potential benefits by providing steady administration of replacement factor to the patient, avoiding high peaks and low troughs. We tested the stability of rFVIII-FS under CI conditions and conducted a single-centre, open-label, phase III study to evaluate the efficacy and safety of CI using rFVIII-FS in haemophilia A patients undergoing surgery. Patients received bolus rFVIII-FS to achieve >or=80% FVIII levels 30-60 min presurgery, followed by CI of rFVIII-FS at a rate calculated to maintain haemostatic factor levels until days 8-10 post surgery. The rate of infusion was adjusted according to daily calculations derived from the actual clearance. The stability of rFVIII-FS was found to be appropriate for CI for 7 days under the same conditions as clinical settings. Fourteen patients (mean age 37.8 years) receiving on-demand FVIII treatment without a history of inhibitors underwent 15 surgical procedures including joint replacements, synovectomies, multiple tooth extractions, and cholecystectomy. Bleeding was similar to that observed in non-haemophilia patients undergoing similar operations in the same department. Haemostasis during surgery was considered by the attending surgeons as 'excellent' or 'good' in all cases; study investigators rated all 15 cases as 'excellent' overall. There were no adverse events, including inhibitor formation, related to rFVIII-FS. rFVIII-FS was found to be suitable for use in CI in haemophilia A patients undergoing major surgery.