Potential role of NovoSeven (R) in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage

Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the ra te of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern t hat recombinant activated factor VII (NovoSeven(R), Novo Nordisk A/S, Bagsv aerd, Denmark) might increase the risk of cerebral ischaemia while stabiliz ing the clot at the site of aneurysmal rupture, an open-label, dose-escalat ion safety study has been developed in collaboration with the UK Spontaneou s Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid hae morrhage verified by computerized tomography scan or lumbar puncture. Safet y evaluation includes clinical observation, monitoring of laboratory variab les, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO(2)) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven(R) 80 mu g/kg single bolus (n = 2), NovoSeven(R) 80 mu g/kg sin gle bolus followed by continuous infusion at 3.5 mu g/kg per h (n = 2) or 7 mu g/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcra nial Doppler ultrasound and PET studies revealed no evidence of cerebral is chaemia in the first nine patients treated with NovoSeven(R). The last pati ent developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation. Blood Coagul Fibrinolysis 11 (suppl 1):S117-S120 (C) 2000 Lippincott Willia ms & Wilkins.