What thrombophilia screening is recommended in cases of recurrent pregnancy loss (RPL)?

From the Guidelines

Thrombophilia screening in cases of recurrent pregnancy loss (RPL) should be selective rather than routine, focusing on women with recurrent early pregnancy losses, a single unexplained loss after 10 weeks, or severe pre-eclampsia leading to birth before 34 weeks. The recommended screening panel includes tests for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein-I), Factor V Leiden mutation, prothrombin gene mutation (G20210A), protein C and S deficiency, and antithrombin deficiency 1.

Key Considerations

• Testing should occur at least 12 weeks after pregnancy or thrombotic events and may need to be repeated for confirmation, particularly for antiphospholipid antibodies which require positive results 12 weeks apart.
• Women with confirmed thrombophilias, especially antiphospholipid syndrome, may benefit from prophylactic treatment with low molecular weight heparin (such as enoxaparin 40mg daily) plus low-dose aspirin (81mg daily) in subsequent pregnancies.
• Certain thrombophilias, particularly antiphospholipid syndrome, increase the risk of pregnancy complications through placental thrombosis and inflammation, and appropriate treatment can significantly improve outcomes in future pregnancies.

Screening Recommendations

• Women with a history of recurrent late-trimester fetal loss should also be considered for testing 1.
• Testing may also be considered in women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine fetal growth retardation, or stillbirth 1.
• Random screening of the general population for factor V Leiden is not recommended 1.

Treatment Implications

• Prophylactic treatment with low molecular weight heparin and low-dose aspirin may be beneficial for women with confirmed thrombophilias, especially antiphospholipid syndrome, in subsequent pregnancies.
• Knowledge of factor V Leiden carrier status may influence management of pregnancy and decision-making regarding oral contraceptive use 1.

From the Research

Thrombophilia Screening in Recurrent Pregnancy Loss (RPL)

Thrombophilia screening is recommended in cases of recurrent pregnancy loss (RPL) to identify potential underlying causes of the condition. The following are some of the key points to consider:

• Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy 2.
• Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation, and protein S deficiency, ideally within a research context 2.
• Inherited thrombophilias have a weak association with recurrent miscarriage, and routine testing for protein C, antithrombin deficiency, and methylenetetrahydrofolate reductase mutation is not recommended 2.
• Thrombophilia screening may be justified in women with pregnancy loss, and treatment with low-molecular weight heparin (LMWH) might be considered in those with pregnancy loss and thrombophilia 3.

Specific Thrombophilic Factors to Consider

Some specific thrombophilic factors that may be associated with RPL include:

• Factor V Leiden, which has been linked to an increased risk of recurrent pregnancy loss 4, 5.
• Antithrombin III deficiency, which may be associated with an increased risk of thrombosis and pregnancy complications 6.
• Protein C and protein S deficiencies, which may also contribute to an increased risk of thrombosis and pregnancy complications 6, 5.
• Hyperhomocysteinemia, which has been associated with an increased risk of thrombosis and pregnancy complications, although the evidence is conflicting 6, 5.

Testing and Treatment

Testing for thrombophilic factors should be considered on a case-by-case basis, taking into account the individual's medical history and risk factors. Treatment with LMWH or other anticoagulants may be considered in women with thrombophilia and a history of pregnancy loss, although the evidence is limited and more research is needed to determine the optimal treatment approach 3, 5.