Prothrombin Gene Mutation Thrombophilia
Let's continue our thrombophilia series with prothrombin gene mutation
What is Prothrombin?
Prothrombin, also known as Factor II, is a clotting factor produced by the liver. It's a precursor protein that gets converted to thrombin during the clotting cascade. Thrombin plays a central role in hemostasis by converting fibrinogen to fibrin and helping to stabilize the blood clot.
What is Prothrombin Gene Mutation?
The prothrombin gene mutation (also called prothrombin G20210A or Factor II mutation) is a variant in the prothrombin gene that results in elevated levels of prothrombin in the blood. The mutation is a single nucleotide change (G to A) at position 20210 in the 3' untranslated region of the prothrombin gene. This leads to increased prothrombin production, which in turn increases the risk of clot formation. Like Factor V Leiden, it can be present in heterozygous or homozygous states.
Prevalence:
2-3% of Caucasian population have heterozygous prothrombin gene mutation
Homozygous state is rare, occurring in less than 0.01% of the population
Less common in Hispanic populations and rare in Asian, African, and Native American populations
Second most common inherited thrombophilia after Factor V Leiden
Risk of VTE:
Heterozygous prothrombin gene mutation increases the risk of developing VTE by 2 to 5 fold
Homozygous prothrombin gene mutation is rare but carries a higher risk, estimated at 10-20 fold increased risk
Like Factor V Leiden, additional risk factors are often present when patients develop clots, such as estrogen/testosterone exposure, immobilization, surgery, pregnancy, or malignancy
Having prothrombin gene mutation does not significantly increase the risk of arterial thrombosis (heart attacks and strokes)
Fun fact: Patients who are compound heterozygotes (having both Factor V Leiden AND prothrombin gene mutation) have a significantly higher VTE risk than either mutation alone - approximately 20-fold increased risk!
Management:
1st Acute VTE episode: same as initial provoked/unprovoked VTE
Recurrent provoked VTE: consider long-term anticoagulation
Recurrent unprovoked VTE: likely benefit from long-term anticoagulation
Pregnancy: close monitoring with consideration for prophylactic anticoagulation based on personal or strong family history of VTE, particularly in the postpartum period when risk is highest
Overall, the VTE risk with prothrombin gene mutation alone is moderate and does not typically warrant prophylactic anticoagulation in the absence of additional risk factors.
Reference: ASH SAP 8th edition, Poort et al, Blood 1996
I hope you found this helpful! In the next post, we'll continue with other inherited thrombophilias.
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