What is the management approach for antiphospholipid syndrome (APS) during pregnancy?

Management of Antiphospholipid Syndrome During Pregnancy

For pregnant women with obstetric APS, combined low-dose aspirin (81-100 mg daily) and prophylactic-dose LMWH is strongly recommended, starting before 16 weeks gestation and continuing through delivery, followed by 6-12 weeks postpartum anticoagulation. 1, 2, 3

Risk Stratification and Treatment Algorithm

Step 1: Confirm APS Diagnosis

• Test for all three antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I) once before or early in pregnancy 4
• Diagnosis requires positive antibodies on two occasions at least 12 weeks apart 2, 5
• Determine if patient meets criteria for obstetric APS (≥3 consecutive miscarriages before 10 weeks, fetal death after 10 weeks, or premature birth before 34 weeks due to preeclampsia/placental insufficiency) or thrombotic APS (history of venous or arterial thrombosis) 1, 6

Step 2: Initiate Treatment Based on APS Type

For Obstetric APS (no prior thrombosis):

• Low-dose aspirin 81-100 mg daily starting before 16 weeks gestation 1, 2, 3
• Prophylactic-dose LMWH (e.g., enoxaparin 40 mg subcutaneously once daily) 1, 2, 3
• Continue aspirin through delivery 3
• Continue anticoagulation for 6-12 weeks postpartum due to persistent thrombotic risk 3, 6

For Thrombotic APS (history of venous or arterial thrombosis):

• Low-dose aspirin 81-100 mg daily 1, 2, 3
• Therapeutic-dose LMWH (e.g., enoxaparin 1 mg/kg subcutaneously twice daily) throughout pregnancy and postpartum 1, 2, 3
• For patients with prior stroke or severe arterial thrombosis, warfarin may be used from 14-34 weeks gestation, though this is controversial 7

For Positive Antibodies Without APS Criteria:

• Prophylactic aspirin 81-100 mg daily is conditionally recommended, particularly for high-risk profiles (triple-positive antibodies, advanced maternal age, IVF pregnancy) 1, 2
• Prophylactic heparin is conditionally recommended against unless individual high-risk circumstances exist 1

Step 3: Consider Adjunctive Hydroxychloroquine

• Conditionally add hydroxychloroquine to standard aspirin/LMWH therapy for patients with primary APS, as recent studies suggest decreased complications 1, 2, 3
• Strongly recommend continuing hydroxychloroquine if patient has SLE and is already taking it 4
• Do not use hydroxychloroquine as monotherapy—it must be added to anticoagulation 4

Management of Refractory Cases

Despite standard therapy, 25-30% of obstetric APS pregnancies result in pregnancy loss 1, 5. For patients who fail standard treatment:

• Consider adding hydroxychloroquine if not already prescribed 1, 4
• Strongly recommend against increasing LMWH dose, as no data demonstrate improved outcomes 1
• Strongly recommend against adding prednisone, as no controlled studies show benefit and risks are significant 1, 4
• Conditionally recommend against intravenous immunoglobulin, though it may be considered in highly refractory cases 1, 7, 8

Monitoring During Pregnancy

• Monthly clinical and laboratory monitoring, with increased frequency in third trimester 6
• Monitor for preeclampsia, HELLP syndrome, placental insufficiency, intrauterine growth restriction, and oligohydramnios 9, 6
• Doppler ultrasound evaluation: persistent notches are the best predictor of placental vascular complications 6
• Anti-Xa monitoring for patients on LMWH, as aPTT is unreliable during pregnancy and especially with lupus anticoagulant present 2, 8
• Plasma heparin levels are needed for optimal anticoagulation monitoring, as standard clotting tests vary greatly during pregnancy 8

Critical Pitfalls to Avoid

• Never use direct oral anticoagulants (DOACs) in APS patients, especially triple-positive patients, due to excess thrombotic events compared to warfarin 2, 3
• Do not discontinue anticoagulation prematurely—thrombotic risk persists postpartum, requiring 6-12 weeks of continued therapy 3, 6
• Avoid estrogen-containing contraceptives in women with positive antiphospholipid antibodies due to significantly increased thrombosis risk 3
• Do not withhold anticoagulation based on thrombocytopenia alone unless critically low or active bleeding present, as thrombocytopenia does not reduce thrombotic risk in APS 3
• Recognize that pregnancy increases thrombotic risk through both hemostatic and anatomic factors, making anticoagulation critical throughout pregnancy and postpartum 1, 9

Assisted Reproductive Technology Considerations

For patients with APS undergoing IVF:

• Start prophylactic LMWH at beginning of ovarian stimulation 2
• Withhold LMWH 24-36 hours prior to oocyte retrieval 2
• Resume immediately following retrieval 2
• Use therapeutic-dose anticoagulation for thrombotic APS patients undergoing ART 2