What is the appropriate low‑molecular‑weight heparin dosing for a pregnant woman with antiphospholipid syndrome, with or without prior thrombosis?

Low Molecular Weight Heparin Dosing for Antiphospholipid Syndrome in Pregnancy

For pregnant women with obstetric APS (≥3 pregnancy losses), use prophylactic-dose LMWH (enoxaparin 40 mg daily or dalteparin 5000 units daily) plus low-dose aspirin 81-100 mg daily throughout pregnancy and for 6-12 weeks postpartum; for thrombotic APS (prior thrombosis), use therapeutic-dose LMWH plus aspirin throughout pregnancy and postpartum. 1, 2, 3

Distinguishing Obstetric vs. Thrombotic APS

The dosing strategy depends entirely on which clinical phenotype the patient has:

Obstetric APS (No Prior Thrombosis)

• Prophylactic-dose LMWH is the standard for women meeting obstetric APS criteria (≥3 early pregnancy losses before 10 weeks OR ≥1 unexplained loss after 10 weeks) 1, 3
• Typical prophylactic dosing: enoxaparin 40 mg subcutaneously once daily or dalteparin 5000 units subcutaneously once daily 2
• Combined with aspirin 81-100 mg daily, started before 16 weeks gestation and continued through delivery 1, 2, 3
• This combination has Grade 1B evidence strength from the American College of Chest Physicians 1, 3

Thrombotic APS (Prior Thrombosis History)

• Therapeutic-dose LMWH is required for women with any history of thrombotic events (venous, arterial, or microvascular) 1, 3
• Therapeutic dosing: enoxaparin 1 mg/kg subcutaneously twice daily or dalteparin 100 units/kg subcutaneously twice daily (or 75% of full therapeutic dose) 3
• Combined with aspirin 81-100 mg daily throughout pregnancy 1, 3
• Continue therapeutic anticoagulation throughout the postpartum period (minimum 6-12 weeks) 1, 3

Timing and Duration

• Start aspirin as early as possible, ideally before 16 weeks gestation, and continue through delivery 1, 2
• Start LMWH after confirmation of pregnancy (or preconceptionally in some high-risk cases) 3, 4
• Continue LMWH throughout all three trimesters without interruption unless bleeding complications arise 1, 3
• Postpartum anticoagulation must continue for 6-12 weeks after delivery due to the prothrombotic postpartum period 1, 3

Dose Adjustment Considerations

• Some evidence suggests adjusted prophylactic dosing (increasing doses as pregnancy progresses and maternal/fetal weight increases) may be beneficial, with one study using 70-80-90 U/kg nadroparin in the first, second, and third trimesters respectively, achieving 97% live birth rate 5
• However, current guidelines primarily recommend fixed prophylactic doses for obstetric APS 1, 2, 3
• Anti-Xa monitoring is not routinely required for prophylactic dosing but may be considered for therapeutic dosing or in patients with extreme body weights 6

Critical Caveats

Asymptomatic aPL-Positive Patients

• Women who are aPL-positive but do NOT meet clinical APS criteria (no thrombosis, <3 pregnancy losses) should NOT routinely receive prophylactic LMWH 1, 3
• These patients should receive aspirin 81-100 mg daily only for preeclampsia prophylaxis 1, 3
• Exception: Consider LMWH in very high-risk scenarios (triple-positive antibodies, strongly positive LAC, advanced maternal age, IVF pregnancy) after shared decision-making 1

Patients with Only Two Miscarriages

• Women with only two miscarriages without confirmed aPL or thrombophilia should NOT receive antithrombotic prophylaxis (Grade 1B recommendation against) 1, 3

Laboratory Confirmation Required

• Treatment should only be initiated after confirmed persistent aPL positivity on two separate occasions at least 12 weeks apart (lupus anticoagulant, anticardiolipin antibodies, or anti-β2-glycoprotein I antibodies) 2, 3, 6

Adjunctive Therapy

• Hydroxychloroquine 200-400 mg daily may be added to standard LMWH plus aspirin therapy for patients with primary APS, as recent studies suggest it may decrease pregnancy complications (conditional recommendation) 1, 2, 6

Peripartum Management

• Discontinue LMWH at least 24 hours before planned delivery or neuraxial anesthesia 3
• Resume LMWH 6-12 hours after vaginal delivery or 12-24 hours after cesarean section once hemostasis is confirmed 3, 4
• Warfarin can be restarted 4-6 hours after vaginal delivery or 6-12 hours after cesarean delivery if long-term anticoagulation is needed for thrombotic APS 4

Common Pitfalls to Avoid

• Do not use vitamin K antagonists in the first trimester (teratogenic) or after week 36 (fetal intracranial bleeding risk) 3
• Do not use direct oral anticoagulants (DOACs) during pregnancy—they are contraindicated due to safety concerns 1, 3
• Do not withhold anticoagulation based on thrombocytopenia alone unless platelet count is critically low or active bleeding is present 6
• Do not use fixed unfractionated heparin when LMWH is available—LMWH is preferred for both prevention and treatment of VTE in pregnancy (Grade 1B) 1