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Factor 7a Recombinant Brand Names- NovoSeven | NovoSeven RT
What is Factor 7a Recombinant (rF7a)
Factor 7a Recombinant (rF7a) is a glycoprotein similar to human plasma-derived factor VII, a vitamin K-dependent clotting factor. Recombinant FVIIa consists of 406 amino acid residues with a molecular weight of 50 kD.
Originally developed for the treatment of patients with hemophilia A or B with inhibitors, rFVIIa is now also used for on-demand treatment and perioperative management of bleeding in patients with acquired hemophilia, factor VII deficiency, and Glanzmann’s thrombasthenia refractory to platelet transfusions.
Before initiating immune tolerance induction (ITI) in patients with hemophilia A and inhibitors, rFVIIa is preferred first-line for the treatment of bleeding to avoid exposure to FVIII contained in activated prothrombin complex concentrates (aPCC) that may trigger anamnesis.
Recombinant FVIIa has also been used off-label in the treatment of von Willebrand’s disease and to normalize prolonged prothrombin time in patients with liver disease or with excessive warfarin dosage.
One of the limitations of recombinant FVIIa treatment is the short dosing interval required to provide therapeutic concentrations. Continuous infusion, compared to intermittent infusion, has been reported to decrease the amount of rFVIIa required by up to 50%.
However, studies have utilized a broad range of dosing with variable efficacy; a clear correlation between doses used and hemostatic efficacy is not always present.
Continuous infusion of rFVIIa is only approved for use in perioperative management during major surgery.
Although there is the potential to induce thrombotic events, rFVIIa has been associated with very few adverse events in both hemophilia and non-hemophilia settings.
Indications
- acquired hemophilia
- coumarin toxicity
- factor VII deficiency
- Glanzmann’s thrombasthenia
- hemophilia A
- hemophilia B
- hemorrhage
- surgical bleeding
- variceal bleeding
- von Willebrand’s disease
For the on-demand treatment and control of hemorrhage and perioperative management of surgical bleeding in patients with hemophilia A or hemophilia B with inhibitors, congenital factor VII deficiency, Glanzmann’s thrombasthenia, or acquired hemophilia
for the on-demand treatment of and control of hemorrhage in patients with hemophilia A or B with inhibitors
Mechanism of Action of Factor 7a Recombinant
Recombinant factor VIIa (rFVIIa) functions as native activated factor VII (FVIIa) in the plasma.
Recombinant factor VIIa may exert its effects through tissue factor (TF) dependent or independent mechanisms or, most likely, a combination of these mechanisms.
TF is normally located in the deeper layers of the vessel wall without any direct contact with the circulation.
Low concentrations of FVIIa are constitutively present in serum accounting for about 1% (4 mg/mL) of the total amount of factor VII protein. At the site of tissue injury, TF and FVIIa form complexes and initiate the extrinsic coagulation cascade by activating factor IX and factor X.
Factor Xa, in combination with other factors, then converts prothrombin to thrombin leading to the formation of a hemostatic plug and local hemostasis by conversion of fibrinogen into fibrin.
At concentrations obtained therapeutically, rFVIIa activates enough factor IX and X on the surface of activated platelets to restore the formation of thrombin by platelets.
This would allow each platelet to produce more thrombin leading to a stable fibrin network even in the absence of an optimal initial platelet plug.
Localization of rFVIIa on activated platelets would tend to restrict the activity of rFVIIa to the sites of injury.
In addition, the platelet surface activity of rFVIIa could explain its effect in patients with thrombocytopenia and platelet function defects
Side Effects
- anaphylactic shock
- anaphylactoid reactions
- angina
- angioedema
- antibody formation
- arthralgia
- disseminated intravascular coagulation (DIC)
- dizziness
- dyspnea
- fever
- headache
- hypertension
- increased intracranial pressure
- infusion-related reactions
- myocardial infarction
- nausea
- phlebitis
- pruritus
- pulmonary embolism
- rash
- stroke
- thromboembolism
- thrombosis
- wheezing
Monitoring Parameters
- activated partial thromboplastin time (APTT)
- clotting inhibitor titers
- factor VII concentrations
- prothrombin time (PT)
Contraindications
- arteriosclerosis
- bovine protein hypersensitivity
- breast-feeding
- cerebrovascular disease
- coronary artery disease
- hamster protein hypersensitivity
- hepatic disease
- murine protein hypersensitivity
- pregnancy
- sepsis
- thromboembolic disease
- thromboembolism
- trauma
Interactions
- Antihemophilic Factor, AHF, Factor VIII
- Antihemophilic Factor, Fc Fusion Protein, Recombinant
- Antihemophilic Factor, Porcine Sequence, Recombinant
- Emicizumab
- Factor IX
- Factor XIII A-Subunit, Recombinant
- Factor XIII Concentrate
- Prothrombin Complex Concentrate, Human
