What is the pharmacologic effect of recombinant factor VIIa (rFVIIa)?

From the Guidelines

Recombinant factor VIIa (rFVIIa) is a potent procoagulant that promotes hemostasis by activating the extrinsic pathway of the coagulation cascade, and its use as an adjunctive treatment for massive bleeding is recommended in certain clinical scenarios, such as blunt trauma, postpartum hemorrhage, and uncontrolled bleeding in surgical patients 1. The pharmacologic effect of rFVIIa is characterized by its ability to bind to tissue factor exposed at sites of vascular injury, leading to activation of factor X to factor Xa, which then converts prothrombin to thrombin, resulting in the formation of a fibrin clot at the site of bleeding. At pharmacologic doses, rFVIIa also directly activates factor X on the surface of activated platelets, bypassing the need for factor VIII or IX, which makes it useful in treating hemophilia patients with inhibitors. Some key points to consider when using rFVIIa include:

• The medication is typically administered as an intravenous bolus at doses ranging from 90-120 mcg/kg, which may be repeated every 2-3 hours until hemostasis is achieved 1.
• The half-life is relatively short (2-3 hours), necessitating repeated dosing for ongoing bleeding.
• Side effects include potential thrombotic complications such as myocardial infarction, stroke, or venous thromboembolism, particularly in patients with underlying risk factors.
• The localized action at sites of tissue damage helps explain why systemic coagulation is not typically activated despite the potent procoagulant effects of this medication. It is essential to carefully evaluate the risks and benefits of using rFVIIa in each patient, taking into account the underlying clinical condition, the severity of bleeding, and the potential for thrombotic complications, as recommended by the European perspective on the use of rFVIIa as an adjunctive treatment for massive bleeding 1.

From the FDA Drug Label

By Treatment Regimen NOVOSEVEN only 44 109 101 (92.7) 2 (1.8) 4 (3.7) 2 (1.8) In HTRS, there were 7 patients that were treated with NOVOSEVEN RT for 23 bleeding episodes. Treatment was reported effective in 21 of 23 (91. 3%) episodes.

The pharmacologic effect of recombinant factor VIIa is to promote hemostasis in patients with bleeding episodes.

• The drug is effective in 92.7% of episodes when used alone.
• It is also effective in 91.3% of episodes in patients treated in the HTRS registry. The main pharmacologic effect is to enhance coagulation and stop bleeding, as supported by studies such as 2.

From the Research

Pharmacologic Effect of Recombinant Factor VIIa

The pharmacologic effect of recombinant factor VIIa (rFVIIa) is to induce hemostasis in patients with bleeding disorders. The key effects of rFVIIa include:

• Enhancement of thrombin generation on activated platelets, leading to the formation of tight hemostatic fibrin plugs resistant to premature lysis 3, 4
• Induction of hemostasis in patients with hemophilia, thrombocytopenia, functional platelet defects, and profuse bleeding triggered by extensive surgery or trauma 3, 4
• Generation of a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury 5

Mechanism of Action

The mechanism of action of rFVIIa involves:

• Binding to the surface of thrombin-activated platelets, leading to enhanced thrombin generation 3, 4
• Interaction with tissue factor to produce a thrombin burst, resulting in accelerated fibrin clot formation 5
• Induction of hemostasis through the formation of tight fibrin hemostatic plugs resistant to premature proteolysis 4

Clinical Use

rFVIIa is used clinically to:

• Treat bleeding episodes in patients with congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders 5
• Provide hemostatic cover during surgery in patients with severe hemophilia and inhibitors 4, 5
• Induce hemostasis in non-hemophilia patients with profuse, heavy bleeding 4, 6

Safety and Efficacy

The safety and efficacy of rFVIIa have been evaluated in several studies, which suggest that:

• rFVIIa is generally well tolerated and effective in treating bleeding episodes and providing hemostatic cover during surgery 5, 6
• High doses of rFVIIa seem to be safe, probably due to its localized effect 4
• rFVIIa should be used with caution in cases with known hypercoagulability, excessive bleeding in the setting of disseminated intravascular coagulation, or other states of generalized activation of the hemostatic system 6