The primary clinical manifestation of prothrombin thrombophilia is VTE. The relative risk for VTE is increased two- to fivefold in 20210GA heterozygotes . Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are the most common VTE. The most common site for DVT is the legs, but upper-extremity thrombosis also occurs.

Source: GeneReviews — "Prothrombin Thrombophilia"

Prothrombin thrombophilia testing may be considered in individuals who have less specific findings, including the following:

Source: GeneReviews — "Prothrombin Thrombophilia"

For high-risk individuals (e.g., those with a history of recurrent VTE, especially at a young age, or those with strong family history of VTE at a young age), evaluation should also include assays of the following:

• Protein C activity

• Antithrombin activity

• Protein S activity or free protein S antigen

Note: Measurement of the following is NOT recommended:

• Plasma concentration of homocysteine, since no data support a change in duration of anticoagulation or the use of vitamin supplementation in individuals with hyperhomocysteinemia and a history of VTE

• MTHFR variants, as no clinical rationale for this testing exists

• Factor VIII and other clotting factor levels

Treatment of Manifestations

Treatment of VTE in Adults

The management of thrombosis in individuals with prothrombin thrombophilia depends on the clinical circumstances. The first acute thrombosis should be treated according to standard guidelines . For initial treatment of VTE, current guidelines suggest a direct oral anticoagulant (dabigatran, edoxaban, rivaroxaban, or apixaban) over warfarin because of a lower bleeding risk and greater co...

Source: GeneReviews — "Prothrombin Thrombophilia"

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

Farah R (2025). [PMID: 39545718](https://pubmed.ncbi.nlm.nih.gov/39545718/). *Haemophilia*. [Epidemiology / Natural History]