Factor II Activity

Factor II is a 72-kilodalton vitamin K-dependent glycoprotein coagulation factor that is produced by the liver.⁶ Normal factor II plasma concentration is approximately 100 mg/mL and half-life is about 60 hours.⁶ Factor II activation occurs by both the extrinsic and intrinsic pathways. Factor II deficiency should be considered when a patient with bleeding history has both extended protime (PT) and activated partial thromboplastin time (aPTT). Inhibitors to factor II may develop in select patients with lupus anticoagulants and tends to occur more frequently in a pediatric population. These inhibitors bind factor II in plasma and clear the antibody-antigen complex resulting in a factor II deficiency and enhanced bleeding potential. A factor II Bethesda (inhibitor) assay is negative in this instance. The dilute Russell's viper venom time (dRVVT) will be prolonged in patients with factor II deficiency.^7,8

Congenital factor II deficiency is rare (fewer than 100 cases have been reported) and is inherited as an autosomal recessive trait.^6,7 This condition affects both males and females, and the prevalence of factor II deficiency is equal in all ethnic groups.⁶ A few cases of combined congenital factor II, VII, IX, and X deficiencies have been reported.⁶ Acquired deficiencies occur with significant hepatic dysfunction, with oral anticoagulant (coumarin) therapy, and in individuals with vitamin K deficiency.^7,8 Diminished levels that can be associated with bleeding can be observed in some patients with lupus anticoagulants due to enhanced clearance of prothrombin/antibody complexes.^6,7

Symptoms of factor II deficiency include easy bruising, hematoma formation, postsurgical hemorrhage, menorrhagia, epistaxis and umbilical cord hemorrhage.^6,7 Heterozygous individuals typically have factor II activities near 50% and are asymptomatic or have minor bleeding complications associated with trauma or surgery.⁷ Factor II plasma activity <30%, as can be observed in individuals with homozygous deficiency, may result in excessive bleeding following a traumatic event.^6,8 Spontaneous bleeding or hemarthroses are rare but may occur in homozygotes with very low activity.^6-8

Factor II activity in excess of 115% has been associated with an increased risk of thrombosis.⁶ The G20210A mutation in the prothrombin gene can be associated with increased plasma prothrombin levels.^6,9 This polymorphism can be identified in 1% to 2% of the US population but is highly race-dependent. This mutation is relatively uncommon in African Americans, Asians and native Americans.⁹ A recent consensus conference of the College of American Pathologists on diagnostic issues in thrombophilia concluded that the prothrombin G20210A mutation is a significant risk factor of venous thromboembolism and should be considered in the initial evaluation of potential inherited thrombophilia.⁹