Background Marzeptacog alfa (activated) (MarzAA), a novel recombinant activated human factor VII (FVIIa) variant, was developed to provide increased procoagulant activity, subcutaneous (SC) administration, and longer duration of action in people with hemophilia. Objectives To investigate if daily SC administration of MarzAA in subjects with inhibitors can provide effective prophylaxis. Methods This multicenter, open‐label phase 2 trial (NCT03407651) enrolled men with severe congenital hemophilia with an inhibitor. All subjects had a baseline annualized bleeding rate (ABR) of ≥12 events/year. Subjects received a single 18 μg/kg intravenous dose of MarzAA to measure 24‐hour pharmacokinetics (PK) and pharmacodynamics (PD), single 30 μg/kg SC dose to measure 48‐hour PK/PD, then daily SC 30 μg/kg MarzAA for 50 days. If spontaneous bleeding occurred, the dose was sequentially escalated to 60, 90, or 120 μg/kg, with 50 days at the final effective dose without spontaneous bleeding to proceed to a 30‐day follow‐up. The primary end point was reduction in ABR. Secondary end points were safety, tolerability, and antidrug antibody (ADA) formation. Results In the 11 subjects, the mean ABR significantly reduced from 19.8 to 1.6, and the mean proportion of days with bleeding significantly reduced from 12.3% to 0.8%. Of a total of 517 SC doses, six injection site reactions in two subjects were reported. No ADAs were detected. One fatal unrelated serious adverse event occurred: intracerebral hemorrhage due to untreated hypertension. Conclusions The data demonstrated that MarzAA was highly efficacious for prophylactic treatment in patients with inhibitors by significantly decreasing bleed frequency and duration of bleeding episodes.

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A 28-year-old man was taken to our hospital with sudden onset of severe headache. The computed tomography (CT) scan revealed subcortical hemorrhage of the right temporal lobe. The patient has past medical history of hemophilia C (XI factor deficiency). On neurological examination no deficit was observed (Glasgow Coma Scale (GCS) -15). 10 hours after admission, his GCS and CT scan of the brain were unchanged. After consultation with the hematologist, he received fresh frozen plasma, mannitol, tranexamic acid during the treatment. But 36 hours after admission, the neurological status was worsened (GCS -12)․ A decision was made to immediately perform a temporal craniotomy with evacuation of intracerebral hematoma. Surgery and the postoperative period were uneventful․ The patient was discharged without neurological deficit․ This case highlights the importance of adequate preparation of the patient presurgically as much as possible to minimizes the risk of complications (rebleeding) during the operation and in the postoperative period.

Հոդվածում քննարկվում է Ժան Պիաժեի կոգնիտիվ զարգացման տեսությունը՝ ժամանակակից կրթական մոտեցումների համատեքստում։