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Therapeutic uses of recombinant coagulation factor VIIa in non-hemophiliacs

Maureane Hoffman, MD, PhD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


A recombinant activated human factor VII produced by transfection of the human factor VII gene into cultured hamster cells is commercially available (Novo-Seven). Its US Food and Drug Administration (FDA)-approved indication in the United States is for promoting hemostasis in individuals with hemophilia who have antibody inhibitors to coagulation factors VIII or IX, patients with acquired hemophilia, and those with congenital factor VII deficiency. This product is licensed in Europe for the above indication as well as for treatment Glanzmann's thrombasthenia [1]. (See "Factor VIII and factor IX inhibitors in patients with hemophilia", section on 'Recombinant human factor VIIa'.)

Early in its development, recombinant FVIIa was investigated as a hemostatic agent in bleeding conditions other than hemophilia. Its apparent safety and utility in a variety of settings, most of which are not supported by clinical trials [2-5], has led to its use in less emergent conditions. It is in these "off-label" settings that most practitioners will encounter the use of rFVIIa.

In this review, we will present an appraisal of the potential benefits, risks, and costs of recombinant human activated factor VIIa in non-hemophilic patients. We recognize that few high-quality studies are available to guide its use in these areas. FVIIa is often used off-label as a rescue therapy when transfusion and other approaches to hemostasis have failed. It is difficult, if not impossible, to obtain informed consent and conduct a randomized trial that reflects the use of a drug in this type of urgent situation. Therefore, the decision to use FVIIa will need to be made on the basis of less than perfect data.

The role of factor VII in coagulation is discussed separately. (See "Overview of hemostasis", section on 'Extrinsic pathway'.)


Patients with hemophilia A or B who develop antibodies to the deficient factor (FVIII or FIX) can be difficult to manage. It is often not possible to neutralize high titer inhibitors even with administration of very high levels of replacement therapy. For this reason, it was a high priority in the 1970s and 80s to develop products that could "bypass" the need for the deficient factor and establish hemostasis in hemophiliacs with inhibitors. Such products are referred to as "bypassing agents." In 1969 prothrombin complex concentrates (PCCs) were noted to improve hemostasis in a patient with hemophilia A with an inhibitor [6]. PCCs are mixtures of the vitamin K-dependent clotting factors prepared from plasma, which were used at that time as a source of coagulation factor IX to treat patients with hemophilia B. Newer products containing increased levels of activated coagulation factors (activated prothrombin complex concentrates or aPCCs) were prepared in an attempt to increase the efficacy of bypassing therapy [7-9]. However, PCCs, and especially aPCCs, were associated with an increased risk of thrombosis [10].


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