What is the recommended management for a 38‑year‑old woman with documented lupus anticoagulant and a prior stillbirth at six weeks gestation?

Management of Lupus Anticoagulant with Prior Early Pregnancy Loss

This patient requires combination therapy with low-dose aspirin (81 mg daily) plus prophylactic low-molecular-weight heparin throughout any future pregnancy, starting when pregnancy is confirmed, along with hydroxychloroquine if she has underlying SLE. 1, 2, 3

Immediate Diagnostic Clarification Needed

Before making treatment decisions, confirm persistent lupus anticoagulant positivity by repeating testing at least 12 weeks after the initial positive result, as transient positivity and false-positives are common and a single test is insufficient for diagnosis. 3 The International Society on Thrombosis and Haemostasis mandates this confirmation before diagnosing antiphospholipid syndrome (APS). 3

• Test for anticardiolipin antibodies (IgG and IgM) and anti-β2-glycoprotein-I antibodies (IgG and IgM) if not already done, as these complete the APS diagnostic workup. 1, 3
• Determine if she has underlying systemic lupus erythematosus through clinical evaluation and serologic testing (ANA, anti-dsDNA, complement levels), as this significantly impacts management. 1

Risk Stratification

This patient has "moderate" risk criteria for obstetric APS based on recurrent early pregnancy loss (though a single stillbirth at 6 weeks technically represents one early loss, not recurrent). 3 However, the presence of lupus anticoagulant alone—even with a single early pregnancy loss—warrants aggressive prophylaxis given that:

• Lupus anticoagulant conveys the greatest risk for adverse pregnancy outcomes with a relative risk of 12.15 for adverse events. 1
• Women with lupus anticoagulant and antiphospholipid antibodies face 2.2 to 5.8 times higher risk of miscarriage, stillbirth, and premature delivery. 1

Preconception Management

Delay pregnancy until any underlying SLE is in stable remission for at least 6 months, as active disease at conception increases flare risk (RR 2.1) and adverse pregnancy outcomes (OR 5.7 for pregnancy loss, 6.5 for preterm delivery). 1, 2, 4

• Optimize disease control before conception with close rheumatology follow-up if SLE is present. 2, 5
• Discontinue teratogenic medications: Stop methotrexate 1-3 months before conception and mycophenolate at least 6 weeks prior. 6
• Continue or initiate hydroxychloroquine if SLE is diagnosed, as it reduces disease activity, prevents flares, and improves obstetrical outcomes. 1, 2, 6

Pharmacologic Management During Pregnancy

Core Antithrombotic Therapy

Start low-dose aspirin (81 mg daily) preconceptionally or immediately when pregnancy is confirmed, no later than 16 weeks gestation. 1, 2, 3, 6 This reduces preeclampsia risk in all high-risk patients. 1

Add prophylactic low-molecular-weight heparin (enoxaparin 40 mg daily or equivalent) when pregnancy is confirmed and continue throughout pregnancy. 1, 2, 3 The combination of aspirin plus LMWH is superior to aspirin alone for obstetric APS and reduces both pregnancy loss and thrombosis. 2, 3, 6

• Do not use aspirin alone—combination therapy with LMWH is required for obstetric APS. 3
• Continue both medications until delivery. 1, 2

If Underlying SLE is Present

Continue hydroxychloroquine throughout pregnancy if already taking it, or start it if not contraindicated. 1, 2, 6 Hydroxychloroquine reduces disease activity, prevents flares, and improves pregnancy outcomes with low fetal risk. 1, 2

Use oral glucocorticoids at the lowest effective dose (ideally ≤7.5 mg/day prednisone equivalent) for disease control if needed. 1, 2 Higher doses are reserved for severe flares. 1

Azathioprine is safe throughout pregnancy for maintenance immunosuppression if required. 1, 2, 4

Calcineurin inhibitors (tacrolimus, cyclosporine) are acceptable for refractory disease during pregnancy. 1, 2

Monitoring Protocol During Pregnancy

Maternal Surveillance

Assess SLE disease activity at least once per trimester through rheumatology and obstetric collaboration, including: 1, 2

• Complete blood count with differential 1
• Urinalysis and urine protein-to-creatinine ratio 1
• Serum creatinine and glomerular filtration rate 1
• Anti-dsDNA antibodies and complement levels (C3, C4) 1

Declining complement levels or rising anti-dsDNA titers indicate possible SLE flare and distinguish lupus activity from preeclampsia. 1

Fetal Surveillance

Perform serial ultrasonography with Doppler studies starting at 20-24 weeks gestation and monthly in the third trimester to detect intrauterine growth restriction and placental insufficiency. 1, 2, 6

Initiate antenatal testing in the third trimester due to increased stillbirth risk. 6

If anti-Ro/SSA or anti-La/SSB antibodies are positive (test if not already done), the risk of congenital heart block is 0.7-2%, but routine serial fetal echocardiography for PR interval assessment is not recommended outside clinical trials. 1, 6

Critical Pitfalls to Avoid

Never diagnose APS based on a single positive test—confirmation at >12 weeks is mandatory. 3

Do not test for lupus anticoagulant while on anticoagulation, as anticoagulants interfere with the assay. 3

Avoid estrogen-containing contraception due to increased thrombosis risk in patients with SLE and antiphospholipid antibodies. 1

Do not use direct oral anticoagulants (DOACs)—they are inferior to warfarin for preventing thromboembolic events in APS. 1

Postpartum Management

Maintain close surveillance for 6-12 weeks postpartum, as this is a high-risk period for both SLE flares (especially renal) and thrombotic events. 1, 2, 4

Hydroxychloroquine, prednisone, and azathioprine are compatible with breastfeeding. 2

Transition to long-term anticoagulation with warfarin (target INR 2.0-3.0) if thrombotic APS criteria are met based on confirmed persistent antiphospholipid antibodies. 1