Aspirin in Recurrent Pregnancy Loss
For women with antiphospholipid syndrome (APS) and recurrent pregnancy loss, aspirin combined with heparin should be used from positive pregnancy test until at least 34 weeks of gestation; for women with unexplained recurrent pregnancy loss or other thrombophilias, aspirin should NOT be used. 1, 2
Women WITH Antiphospholipid Syndrome
Screening and Diagnosis
- Screen for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein-I antibodies) in all women with three or more miscarriages before 10 weeks of gestation 1
- Testing must be positive on two separate occasions to fulfill laboratory criteria for APS 1
Treatment Recommendation
Combined aspirin plus heparin therapy increases live birth rates compared to aspirin alone (live birth rate 78% with combination vs 72% with aspirin alone) 3, 4
- Use low-dose aspirin (75-162 mg daily, typically 81 mg in US practice) starting from positive pregnancy test 1, 5
- Add either low-molecular-weight heparin (LMWH) at prophylactic doses or unfractionated heparin (UFH) 1, 6
- Continue combination therapy until at least 34 weeks of gestation 2
- The combination provides a 27% relative increase in live births compared to aspirin alone (RR 1.27,95% CI 1.09-1.49) 3
Important Nuance on Aspirin Monotherapy
One high-quality randomized trial of 141 women found that aspirin alone achieved a 72% live birth rate in women with APS, which was not significantly different from aspirin plus heparin (78%) 7. However, the most recent guideline evidence and Cochrane systematic review support combination therapy as superior 1, 3, 2.
Women WITHOUT Antiphospholipid Syndrome
Unexplained Recurrent Pregnancy Loss
Aspirin and/or heparin should NOT be given to women with unexplained recurrent miscarriage (two or more losses without identified thrombophilia) 1, 2
- The American College of Chest Physicians explicitly recommends against antithrombotic prophylaxis in this population (Grade 1B recommendation) 1
- The most recent BJOG guideline (2023) reinforces this: aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage 2
- Instead, these women should be offered supportive care in a dedicated recurrent miscarriage clinic 2
Inherited Thrombophilias
For women with inherited thrombophilias (Factor V Leiden, prothrombin mutation, protein C/S deficiency) and history of pregnancy complications, antithrombotic prophylaxis is NOT recommended 1, 6
- The American College of Chest Physicians suggests NOT using antithrombotic prophylaxis for women with inherited thrombophilia and pregnancy complications (Grade 2C) 1
- Do not routinely screen for inherited thrombophilia in women with recurrent pregnancy loss 1, 2
- These thrombophilias have only weak associations with recurrent miscarriage 2
Safety Considerations
Maternal Risks
- Aspirin inhibits platelet function and can contribute to maternal bleeding 8
- Combining aspirin with therapeutic anticoagulation increases bleeding risk without proven benefit 5
- The FDA label cautions against aspirin use during the last 3 months of pregnancy unless directed by a physician, as it may cause problems in the unborn child or complications during delivery 9
Fetal Risks
- Aspirin crosses the placenta and has been associated with increased risk of vascular disruptions, particularly gastroschisis 8
- There is potential risk of premature closure of the ductus arteriosus 8
- However, large trials demonstrate low-dose aspirin's relative safety when used appropriately 8
Common Pitfalls to Avoid
- Do not prescribe aspirin for all women with recurrent pregnancy loss - only those with confirmed APS benefit 1, 2
- Do not use aspirin monotherapy in APS - combination with heparin is superior 1, 3
- Do not screen for or treat inherited thrombophilias with aspirin - no evidence of benefit and potential for harm 1, 6
- Do not confuse preeclampsia prevention with recurrent pregnancy loss prevention - these are distinct indications with different evidence bases 5