To general haemostasis--the evidence-based route

Recombinant factor VIIa (rFVIIa) was developed for the treatment of bleeding in haemophilia patients with inhibitors and has also been used successfully in non-haemophilia patients with acquired antibodies against FVIII (acquired haemophilia). Based on dose-finding trials and a compassionate-use programme, rFVIIa was approved for use in haemophilia patients with inhibitors in 1996. At pharmacological doses, rFVIIa has been found to enhance thrombin generation on already activated platelets. Therefore, it is likely that rFVIIa will also be beneficial in providing haemostasis in other situations characterised by profuse bleedings and an impaired thrombin generation. Patients with thrombocytopenia have a decreased number of platelets and thus an impaired thrombin generation. A reduction in bleeding time was reported in approximately 50% of patients with thrombocytopenia and a prolonged bleeding time who participated in a trial of rFVIIa. Moreover, in 8 patients with 9 overt bleeds who were involved in the study, bleeding stopped in 7 episodes after rFVIIa administration. Case reports on the haemostatic effect of rFVIIa in thrombocytopenia have also been published. Reports have also been published on the successful use of rFVIIa in patients with platelet function deficiencies such as Glanzmann's thrombasthenia and Bernard-Soulier syndrome. A number of haemostatic changes occur after extensive trauma, surgery and bleeding, all of which potentially contribute to an impaired thrombin generation. The effect of rFVIIa has been demonstrated in a number of patients after trauma and bleeds and upper gastrointestinal bleeding episodes. Reports on the beneficial use of rFVIIa in liver transplantation have also been published. Several randomised blinded studies are now underway in e.g. hepatectomy, upper gastrointestinal bleedings, transplantations and intra-cerebral bleeds. In summary, rFVIIa may be an effective and safe method to induce haemostasis in patients within areas of coagulation factor deficiency or platelet disorders and the ongoing and planned randomised studies may lead the way to the use of rFVIIa in general haemostasis.