Human recombinant factor VIIa-is a vitamin K-dependent protein for treatment of bleeding from hemophilia A and B inhibitors, acquired inhibitors, congenital factor VII deficiency.
Recombinant activated factor VII is approved for the treatment of bleeding in patients with hemophilia A or B or who have inhibiting antibodies to factor VIII or IX.
Indications have been increased to include treatment of bleeding episodes and prevention of such episodes related to surgery or invasive procedures in patients with congenital and acquired hemophilia, Factor VII deficiency or Glanzmann’s thrombasthenia.
Human recombinant factor VIIa-complexes to tissue factor and activates factor X to Xa, activates factor IX to IXa and generates thrombin.
A trypsin like serine protease.
An initiator of thrombin generation acts at the site of tissue injury complexed with tissue factor and acts on the surface of platelets, independent of tissue factor.
Forms an active complex with tissue factor which is present in the sub endothelial layer of the blood vessel wall.
Can activate factors IX and X on the platelet membrane, in the absence of tissue factor, and is responsible for the majority of fibrin generated by a local injury.
Human recombinant factor VIIa-reduces surgical blood loss and the need for transfusion in patients undergoing radical retropubic prostatectomy.
Human recombinant activated factor VII reported to be successful in the management of severe traumatic injuries, control the bleeding during surgery, control the bleeding during transplantations, treatment of the intracerebral hemorrhage, and management of bleeding related to anticoagulation therapy ( Levi M et al).
Activated factor VII is administered at doses up to 1000 times the physiological level.
Activated factor VII has a half-life of approximately 2.5 hours.
While recombinant factor VIIa acts by generation of thrombin on from that and-activated platelets and is theoretically localized to the sight of blood vessel wall injury, systemic activation of the coagulation system may occur (Hedner U ey al).
Has been used to reduce heavy bleeding after pregnancy, trauma, back surgery and liver resection.
Human recombinant factor VIIa-can be used in coagulopathies encountered in obstetric, gynecologic patients, with DIC, liver insufficiency and can reverse effects of heparin and warfarin.
With intracerebral hemorrhage the use of activated Factor VII results in improved functional outcome and decreased mortality rate at 3 months (29% to 18%).
With intracerebral hemorrhage use of activated Factor VII result in 3 fold increase in severe arterial and venous thromboembolism at 90 days.
Human recombinant factor VIIa-associated with adverse events in less than 1% of treated patients and include DIC, myocardial infarction and thrombosis.
The use of the recombinant factor VIIa in patients with hemophilia, liver disease, trauma, surgical management, anti-coagulation reversal, and co-agulation disorders in 483 published studies revealed an incidence rate of thromboembolic advance of 1-2% ( Levi M et al).
In the report of the Adverse Event Reporting System of the FDA 185 thromboembolic events occurred in 168 reports involving approved and off label uses of recombinant factor VIIa, although in 38% of cases other hemostatic agents were used as well ( O’Connell KA et al).
In an analysis of 35 randomized clinical trials among 4468 individuals the use of recombinant activated factor VIIa in placebo-controlled trials resulted in significantly increased risk of arterial but not venous thromboembolic events, especially among the elderly ( Levi M et al).
In the above study the rate of coronary arterial thromboembolic events among patients receiving activated factor VIIa was 2.6 times that of patients who received placebo (Levi M et al).
In the above study the risk of arterial thromboembolic advance after activated factor VIIa treatment increased with an odds ratio of 2.4 among patients 65 years of age or older and 3.0 among patients 75 years of age or older, and the rates were higher among patients who received higher doses.
Patients with hemorrhagic stroke randomized to placebo or factor VIIa revealed that there was an increased risk of myocardial infarction and cerebral infarction with 2% vs. 7% events, respectively.
Human recombinant factor VIIa-administration may correct coagulation functions when FFP is ineffective.
In a review of the efficacy and safety of recombinant factor VIIa in patients with hemophilia who had a congenital or acquired inhibitory anti-bodies against factor VIII or IX with approximately 800,000 standard dose is administered a total of 30 thromboembolic events were reported, with six deaths: suggesting the use of recombinant factor VIIa approved for indication of bleeding episodes in patients with hemophilia is associated with a rate of thromboembolic events of less than 1%. (Abeshire T).
In a study of 12 644 hospitalizations for patients who received rFVIIa during a hospital stay 97% of uses were off-label with adult and pediatric cardio-vascuar surgery use 29%, trauma use 29%,and intracranial hemorrhage use 11% (Logan AC et al.
In the above study in-hospital mortality was 27% of patients dicharged to home.