Summary. Recombinant activated factor VII (rFVIIa, NovoSeven 1 ) represents an effective treatment for hemophilia patients with inhibitors, but no consensus as to the best dosing regimen exists. We assessed the efficacy and safety of a rFVIIa 'megadose' (300 mg kg À1 bolus) as treatment for bleeds in three young inhibitor patients. Of 114 bleeds, 95 responded to a single dose. Pain relief was faster and therapy duration significantly shorter than with continuous infusion (CI) regimens or standard boluses (90 mg kg À1 every 3 h). Rebleeding occurred in 9.6% of cases and 19/114 episodes required a second bolus injection. Although rFVIIa consumption per bleed (median: 300 mg kg À1 ) was higher than with standard boluses (180-270 mg kg À1 ), patients found single bolus administration more convenient than recurrent injections or CI. With two exceptions, no complications occurred within 3 h of treatment, despite high FVII:C levels (median: 27.4 U mL À1 ; range: 19.8-54 U mL À1 ). Treatment of bleeds with a rFVIIa megadose in young inhibitor patients is effective and well tolerated.

Background and Purpose-The objective was to investigate the role of infant and maternal thrombophilia in a cohort of mothers and infants presenting with perinatal arterial ischemic stroke. Methods-Forty-seven infants with clinically and radiologically confirmed perinatal arterial ischemic stroke underwent thrombophilia workup: factor V Leiden (FVL), PII20210A mutation, Methylene-tetrahydrofolate reductase 677T polymorphism, protein C, protein S, antithrombin, FVIII, and antiphospholipid antibodies. Thrombophilia data were available for 23 mother-infant pairs and compared with control populations to evaluate the risk for PAS. Results-Thirty of 47 (64%) infants and 15 of 22 mothers (68%) had evidence of thrombophilia. In 18 of 23 (78%) mother-infant pairs, there was at least 1 thrombophilic risk factor, but 15 pairs were mismatched in pathology. Among infants, FVL, protein C deficiency, and presence of antiphospholipid antibodies prevailed (OR, 4.2; 95% CI, 1.5-11.3; OR, 12.2; 95% CI, 2.5-59.9; OR, 4.1; 95% CI, 1.4 -12.2, respectively). Interestingly FVL prevailed in almost one-third of mothers (OR, 8.5; 95% CI, 4.1-17.5) and 18% of mothers had antiphospholipid antibodies (OR, 3.8l; 95% CI, 1.5-10.0). Conclusions-Maternal

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.

Background: An international, multicenter extension study evaluated recombinant fusion protein linking recombinant coagulation factor IX (FIX) with recombinant human albumin (rIX-FP) in hemophilia B (FIX ≤ 2%) patients previously enrolled in a phase III study or who initiated rIX-FP prophylaxis following surgery.Objectives: To investigate the long-term safety and efficacy of rIX-FP prophylaxis in adult previously treated patients (PTPs) with hemophilia B.Methods: Male PTPs were treated with a 7-(35-50 IU/kg), 10-or 14-day regimen (50-75 IU/kg). Patients ≥18 years who were well-controlled on a 14-day regimen for ≥6 months could switch to a 21-day regimen (100 IU/kg). Results:A total of 59 patients (aged 13-63 years) participated in the study. Following a single dose of 100 IU/kg rIX-FP, in patients eligible for the 21-day regimen, the mean terminal half-life was 143.2 hours. Mean steady-state FIX trough activity levels ranged from 22% with the 7-day regimen to 7.6% with the 21-day regimen. Median (Q1, Q3) annualized spontaneous bleeding rates were 0.00 (0.00, 1.67), 0.28 (0.00, 1.10), 0.37 (0.00, 1.68), and 0.00 (0.00, 0.45) for the 7-, 10-, 14-, and 21-day regimens, respectively. Comparable efficacy was demonstrated for both the 14-and 21-day regimens compared to the 7-day regimen. Overall, 96.5% of bleeding episodes were treated successfully with 1 to 2 rIX-FP infusions. No patients developed an inhibitor and treatment was well tolerated.Conclusions: rIX-FP extended interval prophylaxis provides dosing flexibility and, in selected patients, a 21-day regimen may provide an alternative option to minimize treatment burden and individualize treatment.