- Recombinant factor VIIa was initially developed and approved for the treatment of hemophilia and congenital factor deficiencies.
- The recognition of injury-exposed tissue factor (TF) binding to activated factor VII as the principle trigger of clot formation after trauma led to interest in using recombinant factor VIIa for the management of acute traumatic coagulopathy.
- Recombinant human factor VIIa is an adjunctive treatment for coagulopathy associated with trauma, but should be reserved for salvage therapy.
- When used, it is important to correct acidosis, hypothermia, thrombocytopenia, and hypofibrinogenemia prior to its use.
High-dose rFVIIa was originally thought to act by increasing the activity of the extrinsic tissue factor (TF)-associated coagulation pathway, as occurs with physiologic levels of FVIIa at sites of injury However, when administered to supraphysiologic concentrations, rFVIIa binds to the surface of activated platelets in a TF-independent manner and promotes factor X (FX) activation and thrombin generation on the activated platelet surface.
Binding of FVIIa to platelets appears to involve the glycoprotein Ib/IX/V complex and anionic phospholipids expressed on activated platelets. However, additional mechanisms may contribute to platelet binding. A potential role for TF-dependent activity in the hemostatic effect of rFVIIa has not been completely ruled out. This is especially true in certain off-label uses. Because there is a very large amount of TF in the brain, FVIIa may indeed act by a TF-dependent mechanism when used to control intracerebral hemorrhage.
The off-label use of recombinant factor VIIa only for hemorrhage should be reserved for bleeding that has not responded to transfusion or other conventional therapy. Appropriate uses would include patients who are currently experiencing, or are likely to experience, life-threatening bleeding and meet one or more of the following additional criteria:
●No response to, or inability to tolerate, conventional therapy
●Appropriate blood products (eg, compatible red cells) are unavailable or are refused by the patient
●Presence of coagulopathic bleeding
●Bleeding conditions for which no other therapy is available
There is currently no means of determining the optimal dose and dosing regimen of rFVIIa for a given individual or a given condition, and clinical practices vary widely. Since there is no laboratory test that correlates well with the clinical efficacy of rFVIIa, dosing must be determined empirically.
Dosing should be proportionate to the degree of hemostatic impairment and be given before hypothermia and acidosis impair effectiveness of the coagulation system.
At Maine Medical Center, the suggested 1st dose is in the range of 40-80 mcg/kg, using Ideal Body Weight (listed on EPIC).
The half-life of rVIIa in the circulation is 2 hours.
There are few data to guide the duration of therapy. Administration of rFVIIa is generally continued until bleeding has stopped. Additional doses after bleeding has stopped are generally NOT given, in order to minimize the potential risk of thrombosis.
Before giving rVIIa:
- Surgical Bleeding must be controlled
- Platelets must be >50k
- arterial pH >7.2
- correct hypofibrinogenemia
- Body Temperature > 33 C, but higher is better
Contact the MMC Pharmacy (662-3333)
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