From the Guidelines
Heterozygosity for Factor V Leiden is associated with a modest increase in the risk of miscarriage, with a potential 2-3 times higher risk of recurrent pregnancy loss compared to non-carriers. The relationship between heterozygosity for Factor V Leiden and miscarriage risk remains controversial, but current evidence suggests this association 1. Factor V Leiden is a common genetic mutation that causes resistance to activated protein C, leading to increased thrombin generation and a hypercoagulable state. The theoretical mechanism for pregnancy loss involves excessive clotting in placental vessels, potentially compromising blood flow to the developing fetus.
Key Points to Consider
- Women with Factor V Leiden heterozygosity who have experienced recurrent miscarriages may benefit from consultation with a maternal-fetal medicine specialist or hematologist to discuss potential anticoagulation therapy during pregnancy 1.
- Low-molecular-weight heparin (such as enoxaparin 40mg daily) is sometimes prescribed, though this remains somewhat controversial without definitive evidence of benefit.
- The decision to use anticoagulation should be individualized based on personal and family history of thrombosis and pregnancy complications.
- The American College of Chest Physicians suggests antepartum clinical vigilance and postpartum prophylaxis for 6 weeks with prophylactic- or intermediate-dose LMWH or vitamin K antagonists targeted at INR 2.0 to 3.0 for pregnant women with no prior history of VTE who are known to be homozygous for factor V Leiden or the prothrombin 20210A mutation and who do not have a positive family history for VTE 1.
Management and Prevention
- Testing for Factor V Leiden mutation may be important in women with recurrent pregnancy loss, as antithrombotic therapy may be effective in allowing these women to carry a pregnancy to term 1.
- Knowledge of Factor V Leiden status in asymptomatic relatives can be useful in guiding antithrombotic prophylaxis during periods of risk, particularly postpartum, and might allow for heightened awareness of presenting signs of deep vein thrombosis 1.
From the Research
Heterozygosity for Factor V Leiden and Miscarriage Risk
- Heterozygosity for Factor V Leiden has been studied in relation to miscarriage risk, with some studies suggesting an increased risk of miscarriage in carriers of this mutation 2, 3.
- A study published in 2012 found that low-molecular-weight heparin (LMWH) prophylaxis reduced the risk of miscarriages in carriers of Factor V Leiden or prothrombin G20210A mutation, with an odds ratio of 0.52 (95% CI 0.29-0.94) 2.
- Another study published in 2004 found that LMWH was superior to low-dose aspirin in preventing miscarriages in women with heterozygous Factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency, with an odds ratio of 15.5 (95% CI 7-34, P <.0001) 3.
- However, not all studies have found a significant association between heterozygosity for Factor V Leiden and miscarriage risk. A study published in 2020 found no significant difference in miscarriage rates among women with recurrent pregnancy loss and Factor V Leiden mutation who received LMWH, LMWH plus aspirin, or aspirin only 4.
Mechanism of Increased Miscarriage Risk
- The exact mechanism by which heterozygosity for Factor V Leiden increases the risk of miscarriage is not fully understood, but it is thought to be related to the mutation's effect on blood clotting and fibrinolysis 2, 3.
- Factor V Leiden is a prothrombotic mutation that increases the risk of blood clots, which can lead to miscarriage and other pregnancy complications 5.
- LMWH prophylaxis may help reduce the risk of miscarriage in carriers of Factor V Leiden by preventing blood clots and improving fibrinolysis 2, 3.
Clinical Implications
- Women with heterozygosity for Factor V Leiden who have a history of miscarriage or other pregnancy complications may benefit from LMWH prophylaxis to reduce their risk of recurrent miscarriage 2, 3.
- The decision to use LMWH prophylaxis should be made on a case-by-case basis, taking into account the individual woman's medical history and risk factors for miscarriage and other pregnancy complications 4, 2, 3.