THE PROTHROMBIN VARIANT
Franklin A. Bontempo, M.D., Medical Director, Coagulation Laboratory
The recent discovery of a new mutation in clotting factor II, the prothrombin variant (PV), has enhanced the ability of finding a congenital cause of both venous and arterial thrombosis in a significant number of patients.
Prothrombin is the precursor of thrombin (the activated form of factor II) in the clotting cascade and its production leads to the formation of fibrin from fibrinogen.
A nucleotide substitution of G to A at position 20210 in the untranslated portion of the prothrombin gene on chromosome 11 causes an elevation of the level of functional prothrombin in plasma which is associated with an increased risk of thrombosis.
1-2% of studied populations in Europe and the United States have consistently been found to carry the mutation. The frequency in African-Americans is currently estimated to be 0.4%.
Interestingly, as many as 15-40% of thrombotic patients found to be heterozygous for the factor V Leiden mutation have also been found to be carriers of the PV, probably due to the effect of selection. In addition, current estimates are that up to 25% of patients presenting with deep venous thrombosis (DVT) have either the factor V Leiden mutation, the PV, or both.
DIAGNOSIS AND TESTING
PV is diagnosed by a polymerase chain reaction (PCR) test on WBCs usually requiring a yellow top collection tube at room temperature. No plasma-based screening test is available as yet but one is currently under investigation.
Estimates of thrombotic risks, both venous and arterial, in persons heterozygous for the PV compared to the general population are summarized in the following table:
Because only a few patients homozygous for the prothrombin variant have been reported, risk estimates are currently unclear.
Asymptomatic patients with PV are not routinely anticoagulated but are counselled to avoid oral contraceptives, smoking, inactivity, and obesity. Heterozygous patients should be given DVT prophylaxis for surgery and those with 2 or more thrombotic events should receive indefinite anticoagulation. Whether patients with one thrombotic event should receive lifelong anticoagulation is a matter of clinical judgment depending on the patients age, the severity of the initial thrombosis, and whether other prothrombotic risk factors can be altered. Risks and recommendations for pregnant patients are as yet not clearly defined. Screening of selected relatives of patients with PV should be considered in an attempt to determine their thrombotic risk.
The PV is a common prothrombotic mutation associated with both venous and arterial thrombosis, second in frequency among mutations currently described only to factor V Leiden. Testing is recommended for PV when assessing thrombotic risks and making a diagnosis in patients with a suspected prothrombotic tendency.
For questions regarding The Prothrombin Variant, please contact Franklin A. Bontempo, M.D. at (412) 209-7322, or by e-mail: email@example.com
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