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Inherited thrombophilia.


Venous thromboembolism is a common problem in internal medicine practice. The British Committee for Standards in Haematology recently published an update of their 2001 evidence-based guideline to assist clinicians in appropriately using heritable thrombophilia testing in the prevention, screening, and management of thromboembolic disease.


The guideline was restricted to guidance regarding the genetic factors known to increase the risk of venous thromboembolism (VTE) by two or more times (odds ratio, more than 2), specifically antithrombin, protein C, and protein S deficiencies, and factor V Leiden and the prothrombin gene mutations.

Antithrombin, protein C, and protein S deficiencies are considered "severe" or "high-risk" thrombophilias in individuals. Unfortunately, there are no validated criteria to define which families are particularly prone to VTE and should be classified as high-risk families.

Testing of asymptomatic relatives of persons with venous thrombosis has not been demonstrated to reduce the incidence of VTE, and the annual risk of unprovoked clots in family members demonstrated to have thrombophilia is low.

No evidence demonstrates that a heritable factor should lead to modification of the intensity of anticoagulation in a patient with acute VTE.

A first-degree relative with a history of VTE is a relative contraindication to the use of systemic estrogen-containing hormone preparations.

Pregnant women have a 5- to 10-fold increased risk of VTE compared with non-pregnant women; this risk is increased 100 times in women with previous thrombosis.

Persons with VTE prior to age 40 years have been demonstrated to be at increased risk for acute MI; however, the contribution of heritable thrombophilia to risk has not been established.


Testing at the time of an acute venous thrombosis is not indicated; it does not affect acute treatment, and the active thrombotic process can influence some test results.

Testing for heritable thrombophilia is not indicated in unselected patients with a first episode of lower-extremity venous thrombosis (deep vein thrombosis, DVT); pulmonary embolus; or upper-extremity DVT, including those patients with catheter-associated thrombosis. Anticoagulation therapy in VTE patients should be initiated and maintained at the same intensity regardless of the presence of an inherited thrombophilia.

Testing for hereditary thrombophilia in patients following a first episode of intra-abdominal thrombosis or cerebral sinus thrombosis does not clearly predict the risk of recurrence, and it does not provide evidence-based data on which to determine the duration of treatment.

In the majority of patients with VTE, decisions regarding the duration of anticoagulation should be based on whether the initial VTE was provoked, the risk of anticoagulation-related bleeding, and other clinical risk factors. In selected patients, such as those with a strong family history of recurrent unprovoked VTE, testing for an inherited thrombophilia may alter decisions regarding the length of anticoagulation.

Adults who develop skin necrosis associated with the use of coumarins should be tested for protein C and protein S deficiencies. This testing should be performed after the vitamin K antagonist has been discontinued.

Testing of the relatives of patients with antithrombin, protein C, and protein S deficiencies who are in high-risk families may be considered following a discussion of the limitations of the testing and its finely balanced risk/benefit ratio.

Testing of asymptomatic relatives of patients with lower-risk heritable thombophilias (factor V Leiden and the prothrombin gene mutation) is not recommended. Testing family members of patients with more rare thrombophilias is not recommended.

Women who are first-degree relatives of persons with a VTE history and who are being considered for treatment with contraceptives or hormone therapy are recommended to use nonhormonal contraception or transdermal hormone therapy. Testing for heritable thrombophilia is not routinely recommended, as it provides an uncertain risk estimate; testing may be considered in selected women who have a symptomatic relative with a high-risk thrombophilia.

The risk for pregnancy-associated thrombosis should be primarily based on clinical factors. Most women with previous unprovoked VTE, or VTE associated with pregnancy or hormone use, warrant thrombosis prophylaxis based on clinical risk, whereas women with prior VTE associated with trauma or surgery would not require prophylaxis. Thrombophilia testing to guide prophylaxis in pregnancy is recommended for women with prior VTE associated with travel and in women with a family history of unprovoked VTE or VTE associated with pregnancy, hormone therapy, or travel. Testing for thrombophilia is not indicated in patients with arterial thrombosis.


Baglin T, et al. Clinical Guidelines for Testing for Heritable Thrombophilia. Br. J. Haematol. 2010;149:209-20.


DR. GOLDEN (left) is professor of medicine and public health and DR. HOPKINS is program director for the internal medicine/pediatrics combined residency program at the University of Arkansas, Little Roke. Write to Dr. Golden and Dr. Hopkins at
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Author:Golden, William E.; Hopkins, Robert H.
Publication:Internal Medicine News
Geographic Code:1USA
Date:Aug 1, 2010
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