What is the recommended treatment with Low Molecular Weight Heparin (LMWH) for a pregnant woman with Antiphospholipid Syndrome (APS)?

LMWH Treatment for APS in Pregnancy

For pregnant women with antiphospholipid syndrome (APS), initiate combined low-dose aspirin (75-100 mg daily) plus prophylactic-dose LMWH throughout pregnancy and continue anticoagulation for 6-12 weeks postpartum. 1, 2

Risk Stratification Determines Treatment Intensity

The treatment approach depends critically on which APS phenotype the patient has:

Obstetric APS (Recurrent Pregnancy Loss)

• Use prophylactic-dose LMWH plus low-dose aspirin (75-100 mg daily) starting before 16 weeks gestation 1, 2
• This regimen applies to women meeting laboratory criteria (persistent antiphospholipid antibodies on two occasions ≥12 weeks apart) AND clinical criteria of three or more pregnancy losses before 10 weeks 1, 3
• The combination of aspirin plus LMWH increases odds of live birth 7.5-fold compared to no treatment 4
• Continue LMWH through delivery and for 6-12 weeks postpartum 1, 2

Thrombotic APS (Prior Thrombotic Events)

• Use therapeutic-dose LMWH (not prophylactic) plus low-dose aspirin throughout pregnancy and postpartum 1, 2, 3
• These patients require full anticoagulation due to substantially elevated thrombotic risk during pregnancy 1, 5
• If the patient was on warfarin pre-pregnancy, perform frequent pregnancy tests and switch to LMWH immediately upon confirmation of pregnancy 1, 5
• Warfarin can be restarted 4-6 hours after vaginal delivery or 6-12 hours after cesarean delivery 5

Asymptomatic aPL-Positive (No Clinical Criteria)

• Do NOT routinely use LMWH plus aspirin for asymptomatic aPL-positive patients without clinical APS criteria 1, 2, 3
• Consider treatment only in high-risk circumstances: triple-positive aPL, strongly positive lupus anticoagulant, advanced maternal age, or IVF pregnancy—requiring shared decision-making 1, 2
• For preeclampsia prophylaxis alone, use only low-dose aspirin 81-100 mg daily 2

LMWH Superiority Over Unfractionated Heparin

LMWH is strongly preferred over unfractionated heparin for both prevention and treatment of VTE in pregnancy 1, 2, 6. The advantages include:

• More predictable pharmacokinetics during pregnancy 1, 6
• Lower risk of heparin-induced thrombocytopenia 2, 6
• Better patient compliance with once or twice daily dosing 7

Adjunctive Hydroxychloroquine

• Conditionally add hydroxychloroquine to standard LMWH plus aspirin therapy in patients with primary APS 1, 2
• Continue hydroxychloroquine in patients with SLE and APS who are already taking it 2
• Never use hydroxychloroquine as monotherapy—it must be combined with standard anticoagulation 2

Critical Monitoring and Timing Considerations

Laboratory Testing

• Test for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies once before or early in pregnancy—repeat testing does not change management 2
• Lupus anticoagulant carries the highest risk (RR 12.15) for adverse pregnancy outcomes 2, 3

Peripartum Management

• Low-dose aspirin does not typically complicate anesthesia and can continue through delivery in most cases 2
• Discontinue LMWH at least 24 hours before planned delivery or neuraxial anesthesia to minimize bleeding complications 6
• The decision regarding aspirin discontinuation should involve the obstetrician and anesthesiologist based on individual thrombotic risk 2

Common Pitfalls to Avoid

• Never use vitamin K antagonists in the first trimester (teratogenic) or after 34-36 weeks (fetal intracranial bleeding risk) 3, 6
• Avoid all direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) during pregnancy—they are contraindicated 1, 3
• Do NOT prescribe antithrombotic prophylaxis for women with only two miscarriages without confirmed aPL or thrombophilia 1, 3
• Never add prednisone to standard therapy for refractory cases—no controlled studies demonstrate benefit and risks are substantial 1
• Do NOT discontinue LMWH and aspirin prematurely during pregnancy, as this dramatically increases risk of pregnancy loss and thrombosis 2
• Avoid estrogen-containing contraceptives postpartum in women with positive antiphospholipid antibodies due to significantly increased thrombosis risk 2, 8

Special Populations

Systemic Lupus Erythematosus

• The presence of SLE significantly increases risk for preterm birth and preeclampsia beyond APS alone 4
• These patients require particularly close monitoring throughout pregnancy 4

Refractory Cases

• Do NOT increase LMWH dose or add intravenous immunoglobulin for pregnancy loss despite standard therapy—no data support improved outcomes 1
• Pregnancy loss still occurs in 25% of obstetric APS pregnancies despite optimal treatment 1