Factor VII Assay

Factor VII circulates as a single-chain zymogen with a molecular weight of about 50,000 daltons. It has the shortest half-life of the procoagulant factors, approximately 3-6 hours. ^[1] The human factor VII gene is located on chromosome 13, very close to the gene for factor X. ^[1] Research indicates that embryos deficient in factor VII develop normally, without evidence of hemorrhage. Nevertheless, factor VII–deficient newborns sometimes develop fatal intra-abdominal or intracranial hemorrhage. ^{[2, 3]}

The reference range for factor VII is 65-140% of normal. ^[4]

Factor VII is increased in the following:

• Oral contraceptive use and pregnancy

• An increase in factor VII has been associated with thrombophilia

A congenital deficiency of factor VII has been linked to the following :

• Variable hemorrhagic diathesis in homozygotes

Acquired conditions leading to its deficiency include the following:

• Liver disease

• Vitamin K deficiency

• Treatment with vitamin K antagonists

In a survey, Peltier et al found that among 25 patients with congenital factor VII deficiency, initial bleeding symptoms included skin bruising (58%), epistaxis (56%), and menorrhagia (47% of reproductive-age females). Moreover, more than 100 bleeds (any severity) were reported to have occurred in 24% of the patients over the previous year. ^[5]  

See the list below:

• Specimen: Plasma

• Container: Blue-top vacuum tube

• Collection method: Routine venipuncture

All samples must be sent in a sealed, leak-proof container marked with a biohazard sticker to comply with Occupational Safety and Health Administration (OSHA) safety standards.

See the list below:

• Quantitative functional assays of coagulation factors

Description

Factor VII circulates as a single-chain zymogen with molecular weight of about 50,000 daltons. It has the shortest half-life of the procoagulant factors, approximately 3-6 hours. ^[1] The human factor VII gene is located on chromosome 13, very close to the gene for factor X. ^[1]  Research indicates that embryos deficient in factor VII develop normally without evidence of hemorrhage. Nevertheless, factor VII–deficient newborns sometimes develop fatal intra-abdominal or intracranial hemorrhage. ^[2]

Factor VII binds to tissue factor. Once bound to its cofactor, factor VII can be activated by a number of different proteases. Carboxylation by vitamin K is necessary to activate this factor. The physiologic activator of factor VII is thought to be factor Xa, although significant auto-activation by factor VIIa can occur. ^[6] The factor VIIa/TF complex activates both factors IX and X. It is inhibited by tissue factor pathway inhibitor (TFPI) in complex with factor Xa. It is also inhibited by antithrombin (AT), but only in the presence of heparin.

The US Food and Drug Administration (FDA) approved recombinant activated factor VII (synthetic vitamin K–dependent protein) for the treatment of bleeding and perioperative management in patients with hemophilia A or B who have developed inhibitors against replacement coagulation factors. It has also been approved for such use in acquired hemophilia, congenital factor VII deficiency, and Glanzmann thrombasthenia with refractoriness to platelets. Recombinant activated factor VII (rFVIIa) binds to exposed tissue factor at the place of tissue and vascular injury. Thrombin generated by this process activates platelets and the coagulation cascade. It has been used in controlling hemorrhage from surgery, trauma, and other causes with success. ^[7] It has also been found useful in the treatment of obstetrical hemorrhage in women with or without hemophilia.

Indications/Applications

Factor VII testing is indicated when Factor VII deficiency is suspected.

Considerations

Its shortest half-life of all the clotting factors is reflected in the initial rapid prolongation of prothrombin time (INR) in therapy with vitamin K antagonists.

Recombinant FVIIa has also been used to control severe obstetric bleeding in women without hemophilia. ^[8] In that series, bleeding was diminished or arrested in over 80% of patients with no complications due to rFVIIa. However, Lewis et al mention that rFVIIa administration will not be effective if plasma fibrinogen is depleted, particularly if the levels are decreased to 50 mg/dL or less. ^[9]

A concern in rFVIIa use is the specter of thrombosis. ^[7] Thrombotic events may affect as many as 7% of treated patients but appear so far to be uncommon in obstetric patients. ^[10]  (Using Mendelian randomization analysis, de Vries et al found evidence that factor VII activity can be tied to the etiology of ischemic stroke. ^[11] )

Evidence differs, however, regarding the likelihood of thrombosis. A retrospective study by Rajpurkar et al indicated that in the FDA-approved indications for rFVIIa, the risk of thrombotic events is lower than that stated above. For congenital hemophilia with inhibitors, Glanzmann thrombasthenia with refractoriness to platelets, congenital factor VII deficiency, and acquired hemophilia the risk was, respectively, 0.11%, 0.19%, 0.82%, and 1.77%. Risk factors for thrombotic events in rFVIIa use were found to include age of 65 years or above, as well as concomitant cardiac or vascular disease and activated prothrombin complex concentrate use. ^[12]

An intranasal form of desmopressin is also an option for use in hemophilia and is more frequently used at home than the subcutaneous route. A single spray in a single nostril (150 micrograms total dose) is adequate for children more than 5 years old (< 50 kg). A single spray in each nostril is used (300 micrograms total dose) for adolescents (>50 kg) and adults. This dose of intranasal desmopressin increases the factor VIII level by 2-3 times. This therapy can be repeated every 8-12 hours; however, with repetitive use, the patient's stores of factor VIII will be depleted, and, subsequently, the effect will be reduced significantly. Desmopressin is an antidiuretic agent, and fluid restriction may be needed during use. ^[13]

Limitations of the test include partially clotted specimens due to poor mixture of anticoagulant (3:2 sodium citrate as per manufacturer’s blue-topped tube), overfilled or underfilled test tubes altering the ratio of blood to anticoagulant (9:1); improperly stored plasma; contamination with heparin or dilution of collected sample if indwelling catheters are used; or analytical errors such as lipemic, icteric, or hemolyzed plasma, which may interfere with photoelectric measuring instruments. ^[14]