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

Management of Antiphospholipid Syndrome in Pregnancy

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

Risk Stratification and Initial Testing

• Test all pregnant women with APS for lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I antibodies once before or early in pregnancy—do not repeat these tests during pregnancy as they do not change management. 1

• LAC carries the highest risk for adverse pregnancy outcomes (RR 12.15,95% CI 2.92-50.54) compared to other antiphospholipid antibodies. 1

• Distinguish between three clinical phenotypes as treatment differs significantly: asymptomatic aPL-positive patients, obstetric APS (history of pregnancy complications), and thrombotic APS (history of thrombosis). 1

Treatment by Clinical Phenotype

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

• Start prophylactic aspirin 81-100 mg daily before 16 weeks gestation and continue through delivery for preeclampsia prophylaxis. 1

• Do not routinely add heparin/LMWH to aspirin in this population, as the combination is conditionally recommended against. 1

• Exception: Consider adding prophylactic LMWH in high-risk circumstances including triple-positive aPL, strongly positive LAC, advanced maternal age, or IVF pregnancy—these situations require shared decision-making weighing risks versus benefits. 1, 2

Obstetric APS (Prior Pregnancy Complications)

• Initiate combined low-dose aspirin (81-100 mg daily) plus prophylactic-dose LMWH starting in the first trimester and continuing throughout pregnancy. 1

• This combination is strongly recommended based on moderate-strength evidence showing improved live birth rates. 1

• Continue prophylactic-dose anticoagulation for 6-12 weeks postpartum as the thrombotic risk remains elevated during this period. 1

• Consider adding hydroxychloroquine to the standard aspirin plus LMWH regimen for patients with primary APS, as recent studies suggest decreased complications. 1, 3

Thrombotic APS (Prior Thrombotic Events)

• Treat with low-dose aspirin plus therapeutic-dose LMWH throughout pregnancy and postpartum—these patients require full anticoagulation, not prophylactic dosing. 1

• Therapeutic dosing is essential as pregnancy creates additional thrombotic risk through both hemostatic and anatomic factors. 1

Refractory Obstetric APS (Pregnancy Loss Despite Standard Therapy)

• Add hydroxychloroquine to standard aspirin plus prophylactic LMWH therapy when pregnancy loss occurs despite conventional treatment. 3

• Do not add prednisone to standard therapy for refractory obstetric APS—this is strongly recommended against due to lack of controlled studies demonstrating benefit and potential maternal/fetal risks. 1, 3

• Do not increase LMWH dose or add intravenous immunoglobulin as these interventions have not been demonstrably helpful in cases of pregnancy loss despite standard therapy. 1

• Note that prophylactic-dose heparin and aspirin improve likelihood of live birth but not necessarily full-term birth, with pregnancy loss still occurring in 25% of treated obstetric APS pregnancies. 1, 4, 5

Hydroxychloroquine Considerations

• For patients with SLE and APS, strongly continue hydroxychloroquine if already taking it; conditionally start it if not currently taking and no contraindications exist. 1, 3

• Hydroxychloroquine should not be used as monotherapy but rather added to standard anticoagulation therapy. 3

• Do not use prophylactic hydroxychloroquine in pregnant women with positive antiphospholipid antibodies who do not meet APS criteria and lack another indication (such as SLE). 3

Critical Monitoring and Caveats

• Aspirin doses up to 150 mg daily have been used by some investigators, but there is lack of comparative studies showing superiority of doses >100 mg per day. 1

• Low-dose aspirin does not typically complicate anesthesia or delivery, but the decision regarding discontinuation prior to delivery should be made by the obstetrician-gynecologist and anesthesiologist based on the specific clinical situation. 1

• LMWH is preferred over unfractionated heparin due to more predictable pharmacokinetics and lower risk of heparin-induced thrombocytopenia. 6, 7

• Warfarin is contraindicated during pregnancy except possibly between 14-34 weeks for patients with previous stroke or severe arterial thromboses, though this remains controversial. 6

• Avoid estrogen-containing contraceptives in women with positive antiphospholipid antibodies due to significantly increased thrombosis risk. 2, 8, 6