What is the recommended treatment for a pregnant patient with antiphospholipid antibody syndrome, including aspirin and low‑molecular‑weight heparin (enoxaparin or dalteparin) dosing for prophylaxis versus therapeutic anticoagulation, and management of prior thrombotic events or recurrent pregnancy loss?

Treatment of Antiphospholipid Syndrome in Pregnancy

For pregnant patients with antiphospholipid syndrome (APS), the standard treatment is low-molecular-weight heparin (LMWH) combined with low-dose aspirin 75-100 mg daily, with dosing intensity determined by whether the patient has obstetric APS (prophylactic-dose LMWH) or thrombotic APS (therapeutic-dose LMWH). 1

Confirming the Diagnosis Before Treatment

Before initiating therapy, verify that the patient meets both laboratory and clinical criteria:

Laboratory criteria require persistent positivity of antiphospholipid antibodies on two separate occasions at least 12 weeks apart (lupus anticoagulant, anticardiolipin antibodies, or anti-beta-2-glycoprotein I antibodies). 1

Clinical criteria include either:

• Three or more pregnancy losses before 10 weeks gestation, OR
• One or more unexplained losses after 10 weeks, OR
• History of thrombotic events (venous, arterial, or microvascular thrombosis) 1

Treatment Algorithm Based on Clinical Phenotype

Obstetric APS (Recurrent Pregnancy Loss Without Prior Thrombosis)

Start prophylactic or intermediate-dose LMWH plus low-dose aspirin 75-100 mg daily as soon as pregnancy is confirmed. 2, 1 This combination has a Grade 1B recommendation from the American College of Chest Physicians. 2

• Aspirin: Begin preconceptionally or before 16 weeks gestation at 75-100 mg daily 1, 3
• LMWH dosing: Prophylactic dose (e.g., enoxaparin 40 mg daily or dalteparin 5,000 units daily) 1, 4
• Continue throughout pregnancy and for 6 weeks postpartum 1, 4

The mechanism of benefit extends beyond anticoagulation—heparin directly inhibits complement activation induced by antiphospholipid antibodies at the maternal-fetal interface, which is essential for preventing pregnancy loss. 5 Other anticoagulants like fondaparinux or hirudin that lack this complement-inhibiting property do not prevent pregnancy complications in APS. 5

Thrombotic APS (History of Prior Thrombotic Events)

Use therapeutic-dose LMWH (or 75% of therapeutic dose) plus low-dose aspirin 75-100 mg daily throughout pregnancy and postpartum. 1, 6

• LMWH dosing: Therapeutic dose (e.g., enoxaparin 1 mg/kg twice daily or dalteparin 100 units/kg twice daily) 1, 3
• Target anti-Xa level of 0.7-1.2 units/mL measured 4-6 hours after morning dose 4
• Continue for at least 6 weeks postpartum 1, 4

For women on long-term warfarin attempting pregnancy, perform frequent pregnancy tests and immediately substitute LMWH when pregnancy is confirmed rather than switching prophylactically while attempting conception. 2

Asymptomatic Antiphospholipid Antibody-Positive Patients

Do NOT routinely use prophylactic anticoagulation—these patients should receive only prophylactic aspirin 81-100 mg daily for preeclampsia prevention. 1 This is a critical distinction, as asymptomatic antibody positivity without clinical criteria does not warrant full anticoagulation. 1

Critical Peripartum Management

Discontinue LMWH at least 24 hours before planned delivery, cesarean section, or neuraxial anesthesia to reduce hemorrhagic complications. 1, 4 Continue low-dose aspirin unless bleeding is life-threatening. 1

Resume LMWH within 12-24 hours after delivery once hemostasis is achieved, as the postpartum period carries high thrombotic risk. 1 For thrombotic APS, therapeutic-dose LMWH should be resumed. 1

Warfarin can be restarted 4-6 hours after vaginal delivery or 6-12 hours after cesarean delivery if long-term anticoagulation is needed. 3

Adjunctive Therapy Considerations

Hydroxychloroquine may be conditionally added to standard therapy in patients with primary APS, particularly in high-risk cases or those with previous treatment failures. 1, 6 This has emerging evidence for decreased complications. 6, 7

Intravenous immunoglobulin is generally reserved for refractory cases with pregnancy losses despite conventional treatment. 8, 9

Critical Pitfalls to Avoid

Never use direct oral anticoagulants (DOACs) during pregnancy—they are contraindicated due to safety concerns and have shown excess thrombotic events in APS patients compared to warfarin. 1, 6

Avoid vitamin K antagonists in the first trimester (teratogenic risk) and from week 36 onwards (risk of fetal intracranial bleeding). 1

Do NOT withhold treatment in patients with only two miscarriages without confirmed APLA or thrombophilia—these patients should not receive antithrombotic prophylaxis (Grade 1B recommendation against). 2, 1

LMWH is strongly preferred over unfractionated heparin for both prevention and treatment of VTE in pregnancy (Grade 1B). 2, 4 The superior pharmacokinetics, lower bleeding risk, and reduced incidence of heparin-induced thrombocytopenia make LMWH the anticoagulant of choice. 4

High-Risk Features Requiring Intensified Monitoring

Patients with triple-positive antibody profiles (lupus anticoagulant, anticardiolipin, and anti-beta-2-glycoprotein I) carry the highest risk and may require more aggressive management. 6 Lupus anticoagulant alone conveys the greatest risk for adverse pregnancy outcomes (relative risk 12.15). 1

Current standard therapy fails in approximately 20-30% of APS pregnancies, necessitating consideration of additional treatments in high-risk patients. 9, 7