Factor II Activity (Prothrombin)

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Turnaround Time: 2 - 3 days
CPT Code:


Test Type: 1 mL Plasma, frozen


Evaluate an isolated prolonged PT or when there is prolongation of both the aPTT and PT and to document specific factor II deficiency6-8

Direct Xa or thrombin inhibitor therapy may cause factitiously low results.

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

1. Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. Am J Clin Pathol. 1997; 107(1):105-110. PubMed 8980376

2. Reneke J, Etzell J, Leslie S, Ng VL, Gottfried EL. Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant. Am J Clin Pathol. 1998 Jun; 109(6):754-757. PubMed 9620035

3. National Committee for Clinical Laboratory Standardization. Collection, Transport, and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays; Approved Guideline. 5th ed. Villanova, Pa: NCCLS; 2008. Document H21-A5:28(5).

4. Gottfried EL, Adachi MM. Prothrombin time and activated partial thromboplastin time can be performed on the first tube. Am J Clin Pathol. 1997 Jun; 107(6):681-683. PubMed 9169665

5. McGlasson DL, More L, Best HA, Norris WL, Doe RH, Ray H.Drawing specimens for coagulation testing: Is a second tube necessary? Clin Lab Sci. 1999 May-Jun; 12(3):137-139. PubMed 10539100

6. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook. Aurora, Colo: Esoterix-Colorado Coagulation; 2006.

7. Roberts HR, Escobar MA. Less common congenital disorders of hemostasis. In: Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis. Philadelphia, Pa: WB Saunders Co; 2002: 57-71.

8. Triplett DA. Coagulation abnormalities. In: McClatchey KD, ed. Clinical Laboratory Medicine. 2nd ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2002:1033-1049.

9. McGlennen RC, Key NS. Clinical and laboratory management of the prothrombin G20210A mutation. Arch Pathol Lab Med. 2002 Nov; 126(11):1319-1325. PubMed 12421139

Adcock DM, Gosselin R. Direct oral anticoagulants (DOACs) in the laboratory: 2015 review. Thromb Res. 2015 Jul; 136(1):7-12. PubMed 25981138

Collection Details:

Patient Preparation:

Ideally the patient should not be on anticoagulant therapy. Avoid warfarin (Coumadin®) therapy for two weeks prior to the test and heparin, direct Xa, and thrombin inhibitor therapies for about three days prior to testing.

Collection Instructions:

Blue-top (sodium citrate) tube.

Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate.1 Evacuated collection tubes must be filled to completion to ensure a proper blood-to-anticoagulant ratio.2,3 The sample should be mixed immediately by gentle inversion at least six times to ensure adequate mixing of the anticoagulant with the blood. A discard tube is not required prior to collection of coagulation samples unless the sample is collected using a winged (butterfly) collection system. With a winged blood collection set a discard tube should be drawn first to account for the dead space of the tubing and prevent under-filling of the evacuated tube.4,5 When noncitrate tubes are collected for other tests, collect sterile and nonadditive (red-top) tubes prior to citrate (blue-top) tubes. Any tube containing an alternative anticoagulant should be collected after the blue-top tube. Gel-barrier tubes and serum tubes with clot initiators should also be collected after the citrate tubes.