From the Guidelines
For pregnant women with antiphospholipid syndrome, the recommended treatment is a combination of low molecular weight heparin (LMWH) such as enoxaparin and low-dose aspirin, as strongly recommended by the 2020 American College of Rheumatology guideline 1. The standard regimen includes enoxaparin 40 mg subcutaneously once daily (or weight-adjusted at 1 mg/kg once daily or 0.5 mg/kg twice daily for higher risk patients) plus low-dose aspirin (81-100 mg) orally once daily. This treatment should begin as soon as pregnancy is confirmed and continue throughout pregnancy. Key considerations for management include:
- Discontinuing enoxaparin approximately 24 hours before planned delivery to reduce bleeding risk during labor, and resuming 6-12 hours after delivery.
- Stopping aspirin at 36 weeks gestation to minimize bleeding complications during delivery.
- Continuing enoxaparin postpartum for 6 weeks to prevent thrombotic events. The combination of enoxaparin and aspirin works by preventing both placental thrombosis and inflammation - enoxaparin inhibits clotting factor Xa and thrombin, while aspirin reduces platelet aggregation and inflammatory processes in the placenta. Regular monitoring of anti-Xa levels may be necessary to ensure appropriate dosing, especially in women with renal impairment or extreme body weights. Additionally, these patients require close obstetric monitoring with regular ultrasounds to assess fetal growth and placental function, as emphasized in the guideline 1. It's also worth noting that the 2020 American College of Rheumatology guideline conditionally recommends the addition of hydroxychloroquine (HCQ) to prophylactic-dose heparin or LMWH and low-dose aspirin therapy for patients with primary APS, based on evidence suggesting that HCQ may decrease complications 1.
From the Research
Treatment Overview
The recommended treatment for pregnant women with antiphospholipid syndrome involves the use of enoxaparin (low molecular weight heparin) and aspirin (acetylsalicylic acid) [ 2, 3, 4, 5, 6 ].
Key Components of Treatment
- Enoxaparin (Low Molecular Weight Heparin): This is used for prophylactic anticoagulation during pregnancy [ 3 ].
- Aspirin (Acetylsalicylic Acid): Low-dose aspirin is often added empirically to heparin for treatment of antiphospholipid syndrome during pregnancy [ 3 ].
Treatment Protocols
- Most investigators advocate prophylactic-dose heparin plus low-dose aspirin as the preferred treatment for otherwise healthy women with obstetric antiphospholipid syndrome [ 2 ].
- Women with a history of vascular thrombosis alone or associated with pregnancy morbidity are usually treated with therapeutic heparin doses in association with low-dose aspirin [ 2 ].
- Adjusted prophylactic doses of low molecular weight heparin (such as nadroparin) plus low-dose aspirin have been shown to be an efficacious treatment option for pregnant antiphospholipid syndrome patients with no history of thrombosis [ 4 ].
Comparison of Treatments
- The use of low-dose aspirin in combination with low molecular weight heparin during pregnancy for the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome seems to be as safe as unfractionated heparin plus low-dose aspirin [ 5 ].
- Heparin plus aspirin is recommended for women with recurrent pregnancy loss and antiphospholipid syndrome, with unfractionated heparin plus aspirin demonstrating the most significant therapeutic efficacy in improving birthweight [ 6 ].
Important Considerations
- The half-lives of standard heparin or low-molecular-weight heparin, and the peak values for each after subcutaneous injection, are lower than those in nonpregnant patients, requiring dose and injection interval adjustments [ 3 ].
- Clotting tests such as the activated partial thromboplastin time (aPTT) vary greatly during pregnancy and are not useful when the patient has a lupus anticoagulant, making plasma heparin levels necessary for best care [ 3 ].