In a pregnant woman with preeclampsia, when is testing for antiphospholipid antibody syndrome indicated and what is the recommended workup and management?

Testing for Antiphospholipid Antibody Syndrome in Preeclampsia

Test for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I) once in women with early-onset severe preeclampsia (<34 weeks gestation), but do not routinely test all women with preeclampsia. 1, 2

When Testing is Indicated

High-Risk Scenarios Requiring Testing

• Early-onset severe preeclampsia (<34 weeks gestation) is the primary indication for antiphospholipid antibody testing, as 16-20% of these women will have positive antibodies 2, 3
• Eclampsia or HELLP syndrome at any gestational age, particularly when occurring early in pregnancy 4
• Preeclampsia with additional clinical features suggesting APS, including history of thrombosis, recurrent early pregnancy loss, or unexplained fetal death 4

When Testing is NOT Indicated

• Routine screening of all preeclamptic women is not recommended, as the association between isolated antiphospholipid antibodies and preeclampsia without other APS features remains unclear 4
• Preeclampsia occurring at ≥34 weeks gestation does not warrant testing unless other clinical features of APS are present 2
• Repeat testing during the same pregnancy is not recommended once initial testing is completed 1

Recommended Workup

Complete Antibody Panel (Test Once Before or Early in Pregnancy)

The following three antibodies must be tested 1:

• Lupus anticoagulant (LAC) - the most clinically significant antibody associated with adverse pregnancy outcomes 5
• Anticardiolipin antibodies (aCL) - IgG and IgM isotypes
• Anti-β2-glycoprotein I antibodies (anti-β2GPI) - IgG and IgM isotypes

Important Testing Caveats

• Do not repeat antiphospholipid antibody testing during pregnancy, as these antibodies are relatively persistent with unchanged titers 1
• For definitive APS diagnosis, positive results must be confirmed on two separate occasions at least 12 weeks apart 6, though this confirmation testing would occur postpartum
• Women with only low-titer anticardiolipin or anti-β2-glycoprotein I antibodies, or only IgM isotype antibodies, do not meet current classification criteria for APS 5

Management When Antibodies are Positive

Acute Peripartum Management

• Prophylactic anticoagulation should be considered in women with positive antiphospholipid antibodies and early-onset severe preeclampsia, given the 16% rate of thrombotic complications including cerebral infarction, pulmonary embolism, and deep venous thrombosis 3
• Watch for thrombotic microangiopathy, which may initially mimic preeclampsia with severe features but requires different treatment 5
• Standard preeclampsia management takes precedence - delivery remains the definitive treatment for preeclampsia regardless of antibody status 7, 8

Postpartum Considerations

• Extended thromboprophylaxis postpartum is critical, as women with positive antiphospholipid antibodies face substantially elevated thrombotic risk 3
• Confirm diagnosis with repeat testing at least 12 weeks postpartum before labeling the patient with definitive APS 6

Future Pregnancy Planning

• Women with confirmed APS require treatment in subsequent pregnancies with low-dose aspirin (81-150 mg daily) started before 16 weeks gestation and heparin (typically low molecular weight heparin) 1, 6
• Despite standard treatment with heparin and aspirin, 30% of women with definite APS still experience adverse pregnancy outcomes, including recurrent preeclampsia 5, 6

Critical Pitfalls to Avoid

• Do not delay delivery to obtain antibody testing results - preeclampsia management and delivery timing should not be altered based on pending antibody results 7, 8
• Do not assume negative antibodies rule out future APS - antibodies may develop over time, and women with severe early preeclampsia warrant close surveillance in future pregnancies regardless of initial testing 2
• Do not test women with mild preeclampsia at term - the yield is extremely low and does not change management 2, 4
• Recognize that preeclampsia alone does not establish APS diagnosis - current classification criteria require either thrombosis or specific pregnancy morbidities (recurrent early miscarriage, fetal death ≥10 weeks, or severe preeclampsia/placental insufficiency <34 weeks) plus persistently positive antibodies 5, 4