Thrombophilia Testing Recommendations

Key Indications for Thrombophilia Testing

The American College of Medical Genetics recommends testing for patients under age 50 with any venous thrombosis, those with thrombosis in unusual sites, recurrent thrombosis, strong family history of thrombotic disease, and pregnant women or women on oral contraceptives who develop venous thrombosis 1
Testing should be performed in patients with venous thrombosis under age 50, as recommended by the American College of Medical Genetics 2, 1
The American College of Medical Genetics indicates testing for venous thrombosis in unusual sites, such as hepatic, mesenteric, or cerebral veins 2, 1
Recurrent venous thrombosis warrants thrombophilia testing, according to the American College of Medical Genetics 2, 1
Patients with venous thrombosis and a strong family history of thrombotic disease should be tested, as recommended by the American College of Medical Genetics 2, 1
The American College of Medical Genetics recommends testing for venous thrombosis in pregnant women or women taking oral contraceptives 2, 3
Myocardial infarction in female smokers under age 50 is an indication for testing, according to the American College of Medical Genetics 2
Young patients under 50 years who develop acute arterial thrombosis without other risk factors for atherosclerotic disease may benefit from testing, as recommended by the American College of Medical Genetics 2

Venous thrombosis in patients over age 50, except when active malignancy is present, may be considered for testing, according to the American College of Medical Genetics 2
Relatives of individuals known to have factor V Leiden, particularly when knowledge may influence pregnancy management or oral contraceptive use decisions, should be considered for testing, as recommended by the American College of Medical Genetics 2
Women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine growth restriction, or stillbirth should be considered for testing, according to the American College of Medical Genetics 2, 1

Random screening of the general population is not recommended, as stated by the American College of Medical Genetics 2
Routine testing for patients with personal or family history of arterial thrombotic disorders, except specific situations noted above, is not recommended, according to the American College of Medical Genetics 2
Routine screening for asymptomatic women contemplating or using oral contraceptives is not recommended, as stated by the American College of Medical Genetics 3
Screening of asymptomatic individuals with environmental risk factors such as surgery, trauma, paralysis, and malignancy is not recommended, according to the American College of Medical Genetics 3

Either direct DNA-based genotyping or a factor V Leiden-specific functional assay is recommended initially, as stated by the American College of Medical Genetics 2, 1
Patients who test positive by functional assay should undergo confirmatory DNA testing to distinguish heterozygotes from homozygotes, according to the American College of Medical Genetics 2, 1
Patients on heparin therapy or with known lupus anticoagulant should proceed directly to molecular testing, as recommended by the American College of Medical Genetics 2
When testing relatives of individuals with known factor V Leiden, DNA testing is recommended, according to the American College of Medical Genetics 2

When testing for factor V Leiden, consider concurrent testing for other common thrombophilias, particularly prothrombin 20210A mutation, as recommended by the American College of Medical Genetics 4, 1
Protein S, protein C, and antithrombin III deficiencies should be considered, especially with strong family history of venous thrombosis, according to the American College of Medical Genetics 4
Hyperhomocysteinemia should be considered in patients positive for factor V Leiden, as recommended by the American College of Medical Genetics 4, 1

Factor V Leiden homozygotes should be considered for lifetime antithrombotic prophylaxis after a thrombotic event, according to the American College of Medical Genetics 1
Patients heterozygous for both factor V Leiden and prothrombin 20210A mutation have high recurrence risk and should be considered for indefinite anticoagulation, as recommended by the American College of Medical Genetics 1
Knowledge of thrombophilia status can guide prophylaxis decisions during high-risk periods, particularly postpartum, according to the American College of Medical Genetics 1
The risk of major bleeding with chronic warfarin therapy may reach 8% per year, requiring careful risk-benefit assessment, as stated by the American College of Medical Genetics 1

Patients should be informed that thrombophilia testing is genetic, has implications for family members, and may have confidentiality and insurance implications, as recommended by the American College of Medical Genetics 4

The American College of Medical Genetics recommends testing for prothrombin G20210A in all patients who test positive for Factor V Leiden, as it is the most common other thrombophilia with overlapping phenotype for which testing is readily available 5
The prothrombin mutation is present in 1-2% of the general population 5
Its involvement in venous thromboembolism is well-established 5
The DNA test is as simple as that for Factor V Leiden and can even be multiplexed with it 5

The combination of multiple thrombophilias creates synergistic risk that exceeds either mutation alone 5

The American College of Medical Genetics recommends that physicians ordering Factor V Leiden testing should also consider the utility of screening for other heritable thrombophilic factors, especially prothrombin 20210A and plasma homocysteine levels 5
Test for prothrombin G20210A mutation now 5
Consider measuring plasma homocysteine levels as another potential risk factor 5
Functional coagulation assays for Protein S, Protein C, and antithrombin III deficiencies may be considered, especially given the strong family history of thrombophilia 5

Testing should ideally be performed when not on anticoagulation to avoid interference with functional assays, though DNA testing for prothrombin mutation is not affected by anticoagulation status 5