Factor V

Coagulation factor V is a central regulator in the early phases of blood clot formation. It is a large, single chain, glycoprotein which is an essential component in the blood coagulation cascade. During coagulation, the procofactor, factor V, is converted to the active cofactor, factor Va, by thrombin.

Factor Va serves as a cofactor for Factor Xa, both of which assemble assemble on a phospholipid surface in a calcium-dependent manner, to form the prothrombinase complex. This complex can rapidly convert prothrombin to the active serine protease, thrombin. The Factor Va-dependent step increases thrombin generation some 300,000-fold over Factor Xa alone. This potent acceleration of thrombin generation is partly downregulated by Activated Protein C, which inactivates Factor Va.

Genetic deficiency of Factor V results in a rare bleeding disorder called parahemophilia. It is relatively rare and may (even more rarely) also occur in association with Factor VIII deficiency. The disease is similar to hemophilia, except bleeding into joints is uncommon. Bleeding can occur almost anywhere in the body, and death from hemorrhage may occur. Excessive menstrual bleeding and postpartum hemorrhage occurs frequently. Men and women are affected equally.

Factor V deficiency may be suspected in a patient with prolongations of both PT and APTT. However, since similar findings may occur with deficiencies of Factors II and X, specific Factor V assay is necessary to confirm the diagnosis. FV deficiency may be seen in severe liver disease or DIC. Acquired deficiency of FV has also been described as a complication of primary systemic amyloidosis, and in association with Xigris therapy.

Acquired inhibitors to FV occur rarely, but have been described in elderly patients with no prior history of coagulapathy treated with β lactam or aminoglycoside antibiotics, in association with malignant disease or idiopathically.There are reports of patients developing FV inhibitors after a surgical procedure during which topical bovine thrombin or fibrin glue that was prepared from bovine thrombin was used. These products contain small amounts of bovine FV which stimulate the production of antibodies to bovine FV. These neutralizing antibodies cross-react with human factor V, which in turn can cause hemorrhagic complications.

Fresh frozen plasma (FFP) is the usual treatment for Factor V deficiency. In some cases, such as with an acquired factor V inhibitor, platelet transfusions may be effective since they are a source of platelet factor V.

Assays of the coagulation factors are functional measurements of the individual clotting proteins. They are measured by testing the ability of the patient's plasma to correct the clot time of a plasma known to be completely deficient in the clotting factor under test. By comparing the degree of correction with dilutions of a normal plasma, the actual clotting factor level of the test plasma can be calculated. Factor assays are either based on the Prothrombin Time (Factors II, V, VII and X) or the APTT (Factors VIII, IX, XI and XII).

The normal range for Factor V activity in the Hemostasis and Thrombosis Laboratory is 70- 135%.

Please note that Factor V assay is NOT helpful in excluding the presence of the Factor V Leiden gene mutation.

An inhibitor should be suspected if the mixing studies with patient plasma and pooled normal plasma do not correct the prolonged PT and APTT. Further indication of a specific FV inhibitor would include a Factor V assay showing a low activity and a positive Bethesda assay specific for an inhibitor to factor V in the absence of a Lupus Anticoagulant.