الفهرس 
Anatomy & Pathophysiology of HaemostasisOnly 14 pages are availabe for public view
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Abstract
Recombinant FVIIa is a vitamin-K dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. No human serum or proteins are used in the production of rFVIIa. It is manufactured by cloning of the human factor VII gene and is expressed in baby hamster kidney cells, then cultured in bovine albumin. This process eliminates the risk of human blood-borne infection ( Novoseven , 2013 ).
Recombinant FVIIa is a recombinant human coagulation factor that is intended for promoting hemostasis through activation of the extrinsic pathway of the coagulation cascade. It does this by bypassing the coagulation cascade and creating a “thrombin burst”, thereby leading to a stable fibrin clot (Agarwal and Patnaik, 2005 ).
There are numerous theories about the exact mechanism of rFVIIa in vivo. In hemophilia A and B (factor VIII and IX deficiencies), it has been shown that factor VIIa will bind to platelets and activate factor X to factor Xa, resulting in thrombin generation, despite deficiencies in the intrinsic pathway. There has also been shown to be a dose-response relationship between the amount of rFVIIa and thrombin formation, so increasing doses of rFVIIa can increase thrombin generation even in the absence of factor VIII and IX. In addition to upregulation of thrombin formation, it has also been shown that rFVIIa inhibits fibrinolysis by activation of thrombin activatable fibrinolytic inhibitor in factor VIII-deficient plasma (Roberts and White, 2004 ).
rFVIIa was originally developed as a bypassing agent for the treatment of bleeding in hemophilia A and hemophilia B patients with inhibitors to replacement factor VIII and factor IX. However, recent research has supported its use in numerous other hematological conditions. Its safety and efficacy in congenital factor VII deficiency has been shown, and it has been used as prophylaxis for bleeding associated with surgery as well as used in the management of acute bleeding episodes as in severe postpartum hemorrhage, DIC,traumatic bleeding, drug induced coagulopathy, acute intracerebral hemorrhage. Also, it can be used in bleeding due to liver disease, renal failure & platelet disorders (Kubisz and Stasko , 2004 ).
It has been reported that in patients with congenital factor VII deficiency and hemophilia, the half-life of rFVIIa is 2.96 (2.82–3.11) and 2.3 (1.7–2.7) hours, respectively, and therefore it needs to be dosed frequently. According to current recommendations, when used in patients with factor VII deficiency, the doses range from 15 to 30 μg/kg every 4–6 hours, but higher doses may be required for life-threatening hemorrhage ( Novoseven , 2013 ).
Effective treatment requires at least three doses to be administered for adequate hemostasis. These dosage recommendations vary dramatically from the dosing guidelines for patients with hemophilia, in which rFVIIa is currently recommended at 90 μg/kg every 2 hours until hemostasis is achieved. It has been suggested by Tran et al that continuous infusion of rFVIIa during surgery results in the desired hemostasis as well as requiring a significantly reduced amount of rFVIIa, when compared with bolus injections. Such infusional dosing has not become regarded as standard and therefore bolus dosing remains recommended ( Tran et al., 2011).
There have been several case reports which address safety concerns and administration both in the setting of bleeding prophylaxis as well as the complications that may occur. Although bleeding improved in all patients, there are also reports of rFVIIa causing significant side effects. Due to the fact that rFVIIa is a potent thrombin generator, thrombosis resulting in serious events should be of concern to the prescribing physician. Review of the literature reveals reports of cerebral infarction, cerebral ischemia, angina pectoris, myocardial infarction, pulmonary embolism, and deep vein thrombosis. In 2011, Girolami et al reported a series of patients who developed significant thrombotic events after factor replacement, emphasizing that although these patients have severe clotting defects, there is still a risk of thrombosis ( Girolami et al., 2011 ).