Preventing Thrombophilia-Related Complications of Pregnancy

An Update

Shannon M Bates


Expert Rev Hematol. 2013;6(3):287-300. 

In This Article

The Thrombophilias

Thrombophilias are inherited or acquired disorders that are associated with increased risk of thrombosis. Inherited thrombophilias include deficiencies of antithrombin, protein C and protein S, as well as the factor V Leiden and the prothrombin G20210A mutations. While the inherited thrombophilias are generally associated with a propensity to VTE,[9] positivity for the presence of an APLA, an acquired thrombophilia, has been linked to arterial, as well as venous events.[27]

Factor V Leiden Mutation

The factor V Leiden mutation, the most common inherited thrombophilia, is a gain-of-function mutation in which there is impaired cleavage and inactivation of activated factor V (factor Va) resulting in resistance to the action of activated protein C.[28] Heterozygosity for this mutation is associated with a fivefold increased risk of VTE, while homozygotes have an approximately 50-fold increased risk.[29]

Prothrombin G20210A Mutation

The prothrombin G20210A mutation is another gain-of-function mutation in the 3' untranslated region of the prothrombin gene (position 20210) that results in increased amounts of plasma prothrombin.[30] The highest frequencies of the prothrombin gene mutation are seen in individuals of southern European descent (4%). Individuals heterozygous for this mutation have a two to three-fold increase in the risk of VTE.[29]

Antithrombin Deficiency

Antithrombin is a serine protease inhibitor that inhibits thrombin, activated factor Xa and several other activated clotting factors, thereby playing a central role in the control of coagulation.[31] Inherited antithrombin deficiency is relatively rare, occurring in approximately one in 2500 persons. In general, this is considered a high-risk thrombophilia. Homozygous deficiency is exceedingly uncommon, while heterozygous antithrombin deficiency is associated with a ten- to 25-fold increase in the risk of VTE.[31]

Protein S & Protein C Deficiency

Activated protein C, along with its cofactor, protein S, binds to and degrades activated factors V and VIII. Like antithrombin deficiency, deficiencies of these natural anticoagulants are also uncommon.[29]

Antiphospholipid Antibodies

APLAs are autoantibodies directed against phospholipid binding proteins.[27,32] Lupus anticoagulants (nonspecific inhibitors) and anticardiolipin antibodies (ACLA) are commonly the most assayed of these antibodies in clinical practice; however, some centers also test for anti-β2 glycoprotein 1 and other less common ALPAs.[27,33]