What are the diagnostic criteria and treatment options for a young to middle-aged woman with a history of recurrent miscarriages, suspected of having Antiphospholipid Antibody Syndrome (APAS)?

Diagnosis of Antiphospholipid Antibody Syndrome (APAS)

For a woman with recurrent miscarriages, APAS diagnosis requires BOTH persistent laboratory criteria (positive antiphospholipid antibodies on two occasions at least 12 weeks apart) AND clinical criteria (specific pregnancy complications), with treatment consisting of combined low-dose aspirin and prophylactic-dose LMWH throughout pregnancy. 1

Diagnostic Criteria

Laboratory Criteria (Must Be Persistent)

• Test for all three antibodies: lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI) 1, 2
• Positive results must be confirmed on repeat testing at least 12 weeks apart to exclude transient positivity 1
• Moderate-to-high titers are required: ≥40 units (or ≥99th percentile) for aCL and anti-β2GPI 1
• Two positive LAC tests using different detection methods 1

Clinical Criteria for Obstetric APS

The patient must have ONE of the following pregnancy complications (with other causes excluded) 1:

• Three or more consecutive pregnancy losses before 10 weeks gestation 1
• One or more unexplained fetal deaths at or after 10 weeks gestation 1
• One or more premature births before 34 weeks due to preeclampsia, eclampsia, or placental insufficiency 1

Risk Stratification

• Triple-positive patients (all three antibodies positive) carry the highest thrombotic and pregnancy complication risk 1, 2
• LAC positivity is the strongest independent predictor of adverse pregnancy outcomes, with a relative risk of 12.15 for pregnancy complications 1
• Low-titer antibodies may not confer the same risk and do not meet diagnostic criteria 1, 3

Treatment Algorithm

For Confirmed Obstetric APS

Strongly recommend combined therapy: 1, 2

• Low-dose aspirin 81-100 mg daily starting before 16 weeks gestation and continuing through delivery 1
• Prophylactic-dose LMWH (typically enoxaparin 40 mg subcutaneously daily) throughout pregnancy 1, 2
• Consider adding hydroxychloroquine (200-400 mg daily) as recent studies suggest it may decrease complications 1, 2

For Positive aPL Without Meeting Full Obstetric APS Criteria

• Conditionally recommend prophylactic aspirin alone (81-100 mg daily) starting before 16 weeks as preeclampsia prophylaxis 1
• Do NOT routinely add prophylactic heparin unless additional high-risk features present (triple-positive antibodies, advanced maternal age, IVF pregnancy) 1, 2

For Thrombotic APS (History of Blood Clots)

• Therapeutic-dose LMWH (typically enoxaparin 1 mg/kg twice daily) plus low-dose aspirin throughout pregnancy and postpartum 1, 2
• This is a strong recommendation due to high thrombotic risk during pregnancy 1

Critical Pitfalls to Avoid

Testing Errors

• Do not diagnose APS based on single positive test - transient antibodies are common and do not indicate true APS 1
• Be aware of inter-laboratory variability in antibody testing; a positive result in one assay may not reproduce in another 1
• Low-titer antibodies (<40 units) do not meet criteria and management decisions require individualized physician-patient discussion 1

Treatment Errors

• Never use combined estrogen-progestin contraceptives in women with positive aPL due to increased thrombotic risk 1, 3
• Avoid direct oral anticoagulants (DOACs) in triple-positive APS - they are associated with excess thrombotic events compared to warfarin 3, 2
• Do not add prednisone to standard therapy for obstetric APS - no controlled studies show benefit and risks are significant 1
• Do not routinely use intravenous immunoglobulin for refractory pregnancy loss - no demonstrable benefit over standard therapy 1

Monitoring Considerations

• Screen for aPL at multiple time points during pregnancy in women with unexplained recurrent miscarriage, as pregnancy itself can trigger or aggravate antibody production 4
• Continue LMWH postpartum for at least 6 weeks due to persistent thrombotic risk 1
• Women with history of recurrent miscarriages show hypercoagulable state on viscoelastic testing, with prepregnancy MA ≥64 mm having 68% sensitivity and 82% specificity for predicting subsequent miscarriage 1

Special Populations

Assisted Reproductive Technology (ART)

• Start prophylactic LMWH at beginning of ovarian stimulation 2
• Withhold LMWH 24-36 hours before oocyte retrieval, then resume after procedure 2
• Use therapeutic-dose anticoagulation for patients with thrombotic APS undergoing ART 2

Asymptomatic aPL-Positive Patients

• These patients have positive antibodies but no history of thrombosis or pregnancy complications 1
• Do not treat with prophylactic heparin for pregnancy loss prevention 1
• Consider low-dose aspirin for preeclampsia prophylaxis if pregnant 1