eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders
Factor VII: Treatment & Medication
Updated: Feb 14, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Replacement therapy for persons with factor VII deficiency depends on the site and severity of bleeding and the baseline factor VII activity.
- Long-term prophylaxis with 10-50 U/kg 1-3 times per week has been successful in children with severe factor VII deficiency. Mild bleeding associated with bruising and skin lacerations may not require any replacement and can be controlled by applying local pressure at the bleeding site. Minimal mucosal bleeding episodes, such as occurs with epistaxis and during dental procedures, can be managed with antifibrinolytic agents or fibrin glue.
- For spontaneous hemorrhage or mild trauma, therapeutic factor VII levels of 5-10% are sufficient to stop bleeding. This level may be achieved by administering plasma at a dose of 5-10 mL/kg of body weight and repeating the dose every 8-12 hours for 1-2 days.
- For major hemorrhage or surgery, plasma may be administered in a loading dose of 15-20 mL/kg and followed by 3-6 mL/kg every 8-12 hours until the surgical wound heals. This may require 5-7 days of treatment. Plasma infusion may be associated with disadvantages such as volume overload, infectious complications, or an inability to achieve high levels of factor VII. Highly purified factor VII concentrates are useful in patients with severe bleeding or as prophylaxis for surgery. Unlike factor VIII and factor IX deficiencies, for which levels of 100% are required before surgery, factor VII deficiency requires levels in the range of 10-15% to produce efficient hemostasis. For major surgery, trough levels of factor VII must not fall to less than 20 U/dL.
- Prothrombin complex concentrates are also a source of factor VII but carry the risk of infectious complications and thrombosis. When prothrombin concentrates are used, doses of 50 U/kg every 8 hours for 24 hours, followed by plasma infusions, have been shown to be effective for major orthopedic surgery.
- Recombinant factor VIIa (rFVIIa) has proven effective in clinical trials as a treatment for bleeding in hemophilia A patients with inhibitors and in limited numbers of factor VII–deficient patients. rFVIIa is produced by recombinant technology and thus does not carry the risk of infectious complications.
- rFVIIa may be the treatment of choice for previously untreated patients with factor VII deficiency but is currently an expensive treatment. An online registry, the Seven Treatment Evaluation Registry (STER) has been set up, which helps in prospective study to evaluate the efficacy and safety of various therapies with which FVII-deficient patients may be treated.17
- rFVIIa has been effective in the treatment of blood loss associated with various conditions, but reports from larger studies are not yet available to confirm these findings.18
- rFVIIa is reportedly effective in controlling intracranial bleeding when administered within 3-4 hours of onset (from phase II studies, class IIb, level of evidence B), this is being confirmed in larger studies.19
Surgical Care
Prophylactic administration of factor VII concentrates or plasma may help minimize bleeding during surgery. For surgery, factor VII concentrates have been used in doses ranging from 8-40 U/kg every 4-6 hours.
- Fibrin glue or fibrin tissue adhesives have been used as adjunctive therapy to achieve hemostasis. Fibrin glue contains fibrinogen, thrombin, and factor XIII.
- Antifibrinolytic agents such as epsilon-aminocaproic acid and tranexamic acid have been used to enhance hemostasis during dental procedures as an adjunct to replacement therapy.
Consultations
Obtain consultations with orthopedists, physical therapists, general surgeons, dental surgeons, and genetic counselors as needed.
Diet
Instruct patients to maintain a regular, healthy diet without restrictions.
Activity
Recommend that patients limit activity of the involved joints or muscles during acute bleeding episodes. Early physical therapy is recommended once bleeding is resolved to prevent contractures or deformity.
Medication
Recombinant factor VIIa
rFVIIa is licensed by the US Food and Drug Administration for the treatment of bleeding in individuals with hemophilia A and B with acquired inhibitors and for persons with congenital factor VII deficiency. rFVIIa is produced in vitro in baby hamster kidney cells that are transfected with F7.
Although originally developed for the treatment of inhibitor-complicated hemophilia A and B, novel indications for rFVIIa (based on case reports and smaller clinical trials) include use in patients with liver disease, thrombocytopenia, or qualitative platelet dysfunction and in patients with no coagulation disorders who are bleeding as a result of extensive surgery or major trauma.5,20,13,21,22
Antihemophilic agents, drug-product derivatives
The mechanism by which factor VIIa maintains normal hemostasis is unknown. Clot-promoting activity of rFVIIa is primarily mediated through the tissue factor pathway, although direct activation of primary hemostasis may also occur.
Tissue factor-dependent and tissue factor-independent enhancement of thrombin generation have been suggested to play a role.23,21 Factor VIIa alone, in the absence of tissue factor, can generate factor IXa and factor Xa on the surface of activated platelets, which, in turn, induces the coagulation cascade to form thrombin.24
Mechanism of action of rFVIIa in patients with Glanzmann thrombasthenia and Bernard-Soulier syndrome is thought to be from thrombin generation on the surface of platelets, resulting in faster platelet activation and aggregation.5
In a recent study that evaluated rFVIIa in patients with acute intracerebral hemorrhage, the mortality was relatively reduced by 38% at 3 months when rFVIIa was administered within 4 hours of the hemorrhage. Accelerated thrombin generation from activated platelets at the sites of ruptured arterioles after administration of rFVIIa provides hemostatic effect and improved the outcome of these patients.25
By similar mechanisms, rFVIIa is also effective at controlling refractory bleeding in trauma patients.26 Gastrointestinal bleeding in patients with cirrhosis has responded positively to rFVIIa.
Coagulation factor VIIa, recombinant (NovoSeven)
Supplied in 1.2- and 4.8-mg vials. Half-life of rFVIIa is 2-3 h. Cleared from plasma more rapidly in children than in adults.
Adult
35-120 mcg/kg IV bolus q3-6h; dose adjustments made depending on severity of bleeding; in hemophilia A or B with inhibitors, 90 mcg/kg IV bolus q2h
Administration of rFVIIa as a single 270 mcg/kg dose to treat hemarthroses in patients with hemophilia and inhibitors was at least as efficacious and safe as the 90 mcg/kg x 3 regimen, in a multicenter study (Kavakli, 2006)
Bleeding in patients with factor VII deficiency has responded to lower doses (15-20 mcg/kg IV q2-3h) (Roberts, 2004)
The megadose (300 mcg/kg) of rFVIIa in persons with hemophilia is thought to result in higher peaks of thrombin generation and to be effective; this off-label use is not FDA approved
Pediatric
Not established
None reported
Documented hypersensitivity to mouse, hamster, or bovine proteins; DIC; advanced atherosclerotic disease; septicemia; crush injury
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Administer only under direct supervision of physician specialized in management of bleeding disorders; extent of thrombotic events unknown (considered to be low); patients should be monitored for signs and symptoms of activation of coagulation system or thrombosis; if intravascular coagulation or thrombosis confirmed, reduce dosage or cease administration; caution in prolonged administration (limited studies available on posthemostatic dosing); counsel patients on early signs of hypersensitivity reactions; assays of PT, aPTT, and factor VII clotting activity (FVII:c) may yield different results with different reagents (monitor patients for bleeding); avoid simultaneous use of activated prothrombin complex concentrates
Blood products
These agents are indicated for the correction of abnormal hemostatic parameters.
Fresh frozen plasma
FFP is used to correct coagulation factor deficiency when hemostasis is urgently required. FFP is separated within 8 h of whole blood collection and frozen at -18°C. Each unit of FFP contains 200 U of each coagulation factor. Volume transfused should correct factor VII level to at least 30% of normal levels.
Adult
Initial: 15-20 mL/kg IV
Maintenance: 5 mL/kg IV q6-24h
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Carries risk of transmitting viral infections; allergic or anaphylactic reactions occur infrequently; volume overload may occur in patients with poor cardiac reserve
Factor IX complex (Proplex, BeneFix, Hemodyne)
Contains factor VII 68-91 U/mL. Viral inactivation with dry heat (60°C [140°F] for 144 h). Prothrombin complex concentrates contain variable amounts of factors II, VII, IX, and X.
Adult
50 U/kg IV q8h for 24 h, followed by plasma infusion or maintenance prothrombin complex concentrates at 10-20 U/kg IV q6-24h
Pediatric
Administer as in adults
Simultaneous administration with rFVIIa may cause thrombotic complications; risk of thrombosis may increase when used in combination with antifibrinolytic agents
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Earlier preparations of PCCs were themselves associated with a risk of thromboembolic events; more recent preparations have largely eliminated this complication; may induce an anamnestic response
Antifibrinolytic agents
These agents increase circulating plasmin levels and decrease plasminogen levels.
Aminocaproic acid (Amicar)
Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Main problem is that the thrombi that form during treatment are not lysed and effectiveness is uncertain.
Adult
5 g PO initially, followed by 1 g/h PO for 8 doses or until active bleeding controlled, then taper; alternatively, 5 g IV over 30 min to 1 h initially, followed by 1 g/h IV; 1 g q1h or equivalent dose q2-4h PO/IV or 0.1 g/kg q4-6h IV maintenance; not to exceed 30 g/d
Pediatric
100-200 mg/kg IV over 30 min initially, followed by 30 mg/kg IV q1h or 100 mg/kg q6h maintenance; not to exceed 18 g/m2
Coadministration with estrogens may result in hypercoagulable state
Documented hypersensitivity; evidence of active intravascular clotting process
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer unless a definite diagnosis of hyperfibrinolysis has been made; caution in cardiac, hepatic, or renal disease; because aminocaproic acid can be fatal in patients with DIC, important to differentiate between hyperfibrinolysis and DIC; thrombi that forms during treatment are not lysed and effectiveness is uncertain
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References
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Further Reading
Keywords
FVII, F7 gene, proconvertin, stable factor, serum prothrombin conversion accelerator, SPCA, autoprothrombin I, recombinant factor VIIa, rFVIIa, NovoSeven, coagulation, procoagulants, coagulation cascade, anticoagulant factors, Dubin-Johnson syndrome, Rotor syndrome, prothrombin conversion accelerator deficiency, coagulation disorder, blood disorder blood disease, hemophilia A, hemophilia, hemophilia B
