Management of Antiphospholipid Antibody Syndrome in Pregnancy
Pregnant women with antiphospholipid antibody syndrome require combined low-dose aspirin (81-100 mg daily) plus prophylactic-dose LMWH for obstetric APS, or therapeutic-dose LMWH for thrombotic APS, continued throughout pregnancy and for 6-12 weeks postpartum. 1
Risk Stratification and Treatment Algorithm
The management of APS in pregnancy depends critically on whether the patient has obstetric APS (pregnancy morbidity only) versus thrombotic APS (history of thrombosis). 1
For Obstetric APS (≥3 Early Losses or ≥1 Late Loss)
Start combined therapy immediately upon pregnancy confirmation: 1, 2
- Low-dose aspirin 81-100 mg daily – begin before 16 weeks gestation (ideally as early as possible) and continue through delivery 1, 2
- Prophylactic-dose LMWH throughout pregnancy:
- Enoxaparin 40 mg subcutaneously once daily, OR
- Dalteparin 5,000 units subcutaneously once daily 2
- Continue LMWH for 6-12 weeks postpartum due to heightened thrombotic risk after delivery 2
This regimen achieves approximately 70% live birth rates but does not prevent all complications—preeclampsia still occurs in ~34% and preterm delivery in ~43% of treated patients. 3, 4
For Thrombotic APS (Any Prior Thrombotic Event)
Escalate to therapeutic anticoagulation: 1, 2
- Low-dose aspirin 81-100 mg daily throughout pregnancy 1, 2
- Therapeutic-dose LMWH:
- Enoxaparin 1 mg/kg subcutaneously twice daily, OR
- Dalteparin 100 units/kg subcutaneously twice daily (or 75% of full dose) 2
- Continue therapeutic LMWH for minimum 6-12 weeks postpartum 2
The distinction is critical: women with prior thrombosis face compounded risk from pregnancy's hypercoagulable state and require full anticoagulation, not just prophylaxis. 1, 5
For Asymptomatic aPL-Positive Women (No Clinical APS)
Do not routinely use prophylactic LMWH: 1, 2
- Aspirin 81-100 mg daily alone for preeclampsia prophylaxis, started before 16 weeks and continued through delivery 1, 2
- Consider adding prophylactic LMWH only in very high-risk scenarios after shared decision-making:
The 2020 American College of Rheumatology guidelines conditionally recommend against routine LMWH in this population due to insufficient evidence of benefit and known risks (bleeding, heparin-induced thrombocytopenia, osteoporosis). 1, 6
Dosing Adjustments and Monitoring
LMWH Dosing Considerations
Fixed prophylactic doses are recommended for obstetric APS—routine dose escalation during pregnancy is not advised. 2 Current guidelines do not support increasing LMWH doses based solely on advancing gestation or weight gain in the prophylactic setting. 2
Anti-Xa monitoring is not routinely required for prophylactic dosing but may be considered for therapeutic dosing or in patients with extreme body weight. 2 This differs from older practices that advocated routine anti-Xa monitoring.
Peripartum Anticoagulation Management
Discontinue LMWH at least 24 hours before planned delivery or neuraxial anesthesia. 2 This timing allows adequate clearance for safe epidural placement.
Resume LMWH 6-12 hours after vaginal delivery or 12-24 hours after cesarean section once hemostasis is confirmed. 2 The postpartum period carries the highest thrombotic risk, making prompt resumption essential.
Aspirin does not complicate neuraxial anesthesia or delivery and should be continued. 6 The common practice of stopping aspirin before delivery is not evidence-based and may increase thrombotic risk unnecessarily.
Adjunctive Therapies
Hydroxychloroquine
Consider adding hydroxychloroquine 200-400 mg daily to standard therapy for patients with primary APS. 1, 2 This is a conditional recommendation based on emerging small studies suggesting HCQ may decrease pregnancy complications. 1, 7
Do not use HCQ in asymptomatic aPL-positive women without another indication (such as SLE). 1, 6 The evidence is insufficient to justify routine use in this lower-risk population.
Therapies to Avoid
Strongly avoid adding prednisone to standard therapy—no controlled studies demonstrate benefit, and the risk profile is unfavorable. 1, 2
Do not use intravenous immunoglobulin or increased LMWH doses for refractory cases—these have not been demonstrably helpful despite anecdotal reports. 1, 2
Never use vitamin K antagonists (warfarin) in the first trimester (teratogenic) or after 36 weeks (risk of fetal intracranial hemorrhage). 6 Direct oral anticoagulants are contraindicated throughout pregnancy. 6
Monitoring Protocol During Pregnancy
Maternal Surveillance
Schedule rheumatology or high-risk obstetric visits at least monthly, increasing to every 2-4 weeks for triple-positive or lupus anticoagulant-positive patients. 6
Check blood pressure at every prenatal visit—preeclampsia occurs 2.3-fold more frequently in APS. 6
Perform laboratory monitoring at least once per trimester: 6
- Complete blood count
- Urinalysis with protein-to-creatinine ratio
- Serum creatinine
- Complement C3/C4 levels (if concurrent SLE)
- Anti-dsDNA antibodies (if concurrent SLE, to differentiate flare from preeclampsia)
Fetal Surveillance
Begin serial ultrasounds with Doppler at 16-20 weeks: 6
- Detailed anatomic survey at 20-24 weeks with baseline uterine and umbilical artery Doppler
- Monthly third-trimester Doppler assessments beginning at 28 weeks (umbilical artery, uterine arteries, ductus venosus, middle cerebral artery)
- Increase to every 1-2 weeks after 32 weeks or sooner if abnormalities detected
Monitor for intrauterine growth restriction (IUGR), which occurs 4.7-fold more frequently in high-risk APS. 6 After 34 weeks, do not rely solely on umbilical artery Doppler—incorporate cerebro-placental ratio and abdominal circumference growth velocity. 6
Common Pitfalls and How to Avoid Them
Do not withhold anticoagulation based on thrombocytopenia alone unless platelet count is critically low or active bleeding is present. 8 Thrombocytopenia is common in APS and does not contraindicate treatment.
Do not assume normal complement levels exclude an SLE flare—look for declining trends even within the normal range. 6 Pregnancy physiologically increases complement, so "normal" values may represent a relative decrease.
Do not discontinue aspirin before delivery solely due to anesthesia concerns—aspirin generally does not interfere with neuraxial anesthesia. 6
Do not use the same regimen for obstetric and thrombotic APS—the latter requires therapeutic, not prophylactic, anticoagulation. 1, 2 This is a critical distinction that directly impacts maternal mortality risk.
Laboratory Confirmation Requirements
Treatment should be initiated only after persistent aPL positivity is documented on two separate occasions ≥12 weeks apart (lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein I antibodies). 2, 8 Single positive tests are insufficient for diagnosis and do not justify treatment.
Test all three criteria antibodies—lupus anticoagulant carries the highest risk (relative risk ~12 for adverse pregnancy outcomes) and must be specifically evaluated. 8, 6 Triple positivity indicates the highest risk for both thrombotic events and pregnancy complications. 8, 6
Postpartum Management
Continue therapeutic anticoagulation for 6-12 weeks postpartum in all APS patients. 2 The postpartum period represents the highest thrombotic risk window, with three patients in one cohort experiencing recurrent cerebral ischemic events during this time despite treatment. 4
Monitor blood pressure and symptoms postpartum to detect postpartum preeclampsia. 6 Preeclampsia can present for the first time after delivery, particularly in APS patients.