What is the recommended treatment for antiphospholipid syndrome (APS) in pregnancy?

Management of Antiphospholipid Syndrome in Pregnancy

For pregnant women with antiphospholipid syndrome (APS), the recommended treatment is low-dose aspirin (81-100 mg daily) combined with heparin (preferably low-molecular-weight heparin) throughout pregnancy and postpartum. 1, 2

Treatment Based on APS Classification

Obstetric APS

• First-line therapy:
  • Low-dose aspirin (81-100 mg daily) starting early in pregnancy (before 16 weeks) and continuing through delivery 1, 2
  • PLUS prophylactic-dose LMWH starting when pregnancy is confirmed 1
  • Continue prophylactic anticoagulation for 6-12 weeks postpartum 1

Thrombotic APS

• First-line therapy:
  • Low-dose aspirin (81-100 mg daily) 1
  • PLUS therapeutic-dose heparin (usually LMWH) throughout pregnancy and postpartum 1

Asymptomatic aPL-positive patients (without APS)

• Low-dose aspirin (81-100 mg daily) as preeclampsia prophylaxis 1
• Treatment should begin early (before 16 weeks) and continue through delivery 1
• Combination therapy with prophylactic heparin is generally not recommended unless there are additional risk factors 1

Medication Details

Low-Molecular-Weight Heparin (LMWH)

• Preferred over unfractionated heparin for prevention and treatment of VTE in pregnant women 1
• Dosing:
  • Prophylactic dose for obstetric APS
  • Therapeutic dose for thrombotic APS
  • Some evidence suggests adjusting doses as pregnancy progresses (70-80-90 U/kg in first, second, and third trimesters respectively) 3

Aspirin

• Low-dose (81-100 mg daily) 1, 2
• Begin early in pregnancy (before 16 weeks) 1
• Continue through delivery 1

Additional Therapies for Refractory Cases

Hydroxychloroquine (HCQ)

• Conditionally recommended as an addition to standard therapy (LMWH + aspirin) for patients with primary APS 1, 2
• Recent studies suggest HCQ may decrease complications in APS pregnancies 1, 2

Therapies NOT Recommended

• Intravenous immunoglobulin (IVIG): Not recommended as standard therapy; limited evidence for use in recurrent pregnancy loss despite standard therapy 2
• Increased LMWH dose: Not recommended for cases of pregnancy loss despite standard therapy 1
• Prednisone: Strongly recommended against adding to standard therapy due to lack of evidence showing benefit and potential risks 1

Treatment Outcomes and Monitoring

• Standard therapy (LMWH + aspirin) improves likelihood of live birth but not necessarily full-term birth 1
• Pregnancy loss occurs despite treatment in approximately 25% of obstetric APS pregnancies 1
• Regular monitoring is essential:
  • Clinical assessment
  • Laboratory monitoring (platelet count)
  • Fetal monitoring for growth restriction or placental insufficiency 2

Important Considerations

• Risk stratification: Triple positivity (positive for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies) confers the highest risk for adverse outcomes 2
• For women requiring long-term vitamin K antagonists who are attempting pregnancy, frequent pregnancy tests are recommended with LMWH substitution when pregnancy is achieved 1
• Preeclampsia, fetal distress, fetal growth impairment, and premature delivery are common complications despite treatment 4

This treatment approach has been shown to improve live birth rates to 70-80% in women with APS compared to much lower rates without treatment 2, 5.