What is the recommended treatment for Antiphospholipid Syndrome (APS) in pregnancy?

Treatment of Antiphospholipid Syndrome in Pregnancy

For pregnant women with obstetric APS, treat with combined low-dose aspirin (81-100 mg daily) plus prophylactic-dose LMWH throughout pregnancy and continue anticoagulation for 6-12 weeks postpartum. 1

Treatment Algorithm by Clinical Phenotype

Obstetric APS (History of Pregnancy Loss)

• Start low-dose aspirin (81-100 mg daily) before 16 weeks gestation and continue through delivery 1
• Add prophylactic-dose LMWH (e.g., enoxaparin 40 mg daily subcutaneously) throughout pregnancy 1
• Continue anticoagulation for 6-12 weeks postpartum due to persistent thrombotic risk 2, 3
• Consider adding hydroxychloroquine to the aspirin-LMWH regimen for patients with primary APS, as recent studies suggest decreased complications 1, 2

This combination improves live birth rates to approximately 68-73%, though pregnancy loss still occurs in 25% despite treatment 1, 4, 5

Thrombotic APS (History of Thrombosis)

• Use low-dose aspirin plus therapeutic-dose LMWH (e.g., enoxaparin 1 mg/kg twice daily) throughout pregnancy and postpartum 1, 2
• These patients require full anticoagulation, not prophylactic dosing, due to substantially elevated thrombotic risk 3
• Warfarin can be considered from 14-34 weeks for patients with previous stroke or severe arterial thrombosis, though LMWH is preferred 6

Asymptomatic aPL-Positive (No Prior Thrombosis or Pregnancy Loss)

• Prophylactic aspirin alone (81-100 mg daily) starting before 16 weeks and continuing through delivery for preeclampsia prophylaxis 1
• Do not routinely add heparin/LMWH to aspirin in this group 1
• Exception: Consider aspirin plus prophylactic LMWH in high-risk circumstances including triple-positive aPL, strongly positive lupus anticoagulant, advanced maternal age, or IVF pregnancy after shared decision-making 1, 3

Critical Risk Stratification

Lupus anticoagulant (LAC) carries the highest risk for adverse pregnancy outcomes with a relative risk of 12.15 compared to other antiphospholipid antibodies 1, 3

High-risk antibody profiles requiring more aggressive management include: 2, 7

• Triple-positive (LAC + anticardiolipin + anti-β2GPI)
• Double-positive with LAC
• Isolated LAC positivity

Refractory APS Management

For patients with pregnancy loss despite standard aspirin-LMWH therapy, do NOT add: 1

• Prednisone (strongly recommended against—no controlled studies show benefit and significant risk)
• Increased LMWH dose (no data demonstrating improved outcomes)
• Intravenous immunoglobulin (only anecdotal data, not demonstrably helpful)

Consider hydroxychloroquine as adjunctive therapy for refractory cases, particularly in patients with SLE 1, 2

Monitoring and Complications

Expect high rates of obstetric complications even with treatment: 4

• Preeclampsia occurs in ~50% of pregnancies
• Fetal distress in ~50%
• Fetal growth restriction in ~30%
• Preterm delivery required in 37% due to maternal or fetal indications

LMWH is preferred over unfractionated heparin due to more predictable pharmacokinetics and lower risk of heparin-induced thrombocytopenia 3, 8

Critical Pitfalls to Avoid

• Never use direct oral anticoagulants (DOACs) in APS patients, particularly triple-positive patients, due to excess thrombotic events compared to warfarin 2, 7
• Avoid estrogen-containing contraceptives in women with positive antiphospholipid antibodies due to significantly increased thrombosis risk 2, 3
• Do not withhold anticoagulation based on thrombocytopenia alone unless platelet count is critically low or active bleeding is present—thrombocytopenia does not reduce thrombotic risk in APS 2
• Do not use hydroxychloroquine as monotherapy—it should only be added to standard anticoagulation therapy 3
• Confirm antibody persistence—diagnosis requires positive antibodies on two occasions at least 12 weeks apart 2, 7

Special Considerations

For patients with SLE and APS: 3

• Strongly recommend continuing hydroxychloroquine if already taking it
• SLE significantly increases risk for preterm birth and preeclampsia 5

Low-dose aspirin does not typically complicate anesthesia or delivery, but timing of discontinuation should be coordinated with obstetrics and anesthesiology based on individual bleeding risk 3