Recombinant activated factor VIIa in uncontrolled bleeding: a haemostasis laboratory study in non-haemophilia patients

Abstract

Extensive surgery and massive tissue trauma are often associated with severe bleeding. We present retrospective data on the use of recombinant factor VIIa in haemostatic emergencies in13 non-hemophilia patients with uncontrolled bleeding. Recombinant factor VIIa was administered in doses ranging from 16 mug/kg bodyweight to 60 microg/kg bodyweight. Blood loss during 24 h before and after the infusion was registered, showing that 10 out of 13 patients (77%) had a 70% or greater reduction in transfusion requirement decreasing significantly in mean from 28.1 to 9.9 red blood cell units. Coagulation parameters were studied in blood samples collected 10 min before and 10-15 min after the injection of recombinant factor VIIa. Factors VII:C, II:C, and X:C increased significantly while the activated partial thromboplastin time, platelet numbers, and concentration of fibrinogen and D-dimers were unchanged. The dose of rFVIIa correlated significantly with the rise in factor X:C and inversely with transfusion requirements. Dynamic clot velocity of whole blood was recorded before and after rFVIIa infusion in four patients. Judged from red blood cell usage no improvement in haemostasis was seen in one patient suffering thrombocytopenia and low fibrinogen. This patient died 6 h after recombinant factor VIIa infusion, and three other patients died before 1 month. None of the fatalities appeared to be related to recombinant factor VIIa usage. No thromboembolic complications were seen. In conclusion, 12 out of 13 patients survived the first 24 h after treatment with relatively low doses of recombinant factor VIIa for large-scale bleeding. Recombinant factor VIIa was well tolerated and safe in these non-hemophilia patients. With quite low doses of recombinant factor VIIa (<or= 60 microg/kg), the dose of recombinant factor VIIa correlated positively with efficacy. Activation of factor X appeared to predict haemostatic efficacy.