Antiphospholipid Antibody Testing in Early-Onset Severe Preeclampsia
Yes, antiphospholipid antibody testing should be performed in pregnant women with early-onset severe preeclampsia (before 34 weeks), particularly when accompanied by personal or family history of thrombosis, unexplained fetal loss, or other obstetric complications. 1, 2
Who Should Be Tested
Test for antiphospholipid antibodies in the following clinical scenarios:
- Women with severe preeclampsia presenting before 34 weeks' gestation 2, 3
- Women with eclampsia at any gestational age 4
- Women with HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) 4, 2
- Women with recurrent early pregnancy loss (three or more miscarriages before 10 weeks) 1
- Women with personal history of thrombosis 1
- Women with family history of thrombosis or unexplained fetal loss 1
The rationale is compelling: approximately 16-20% of women with early-onset severe preeclampsia (before 34 weeks) have elevated antiphospholipid antibodies, compared to essentially 0% in normotensive controls 2, 3. This association is specific to early-onset disease and not found in preeclampsia occurring after 34 weeks 2.
Complete Testing Panel Required
Order all three antiphospholipid antibody tests simultaneously:
- Lupus anticoagulant (LAC) - conveys the greatest risk for adverse pregnancy outcomes (RR 12.15) 1
- Anticardiolipin antibodies (aCL) - both IgG and IgM isotypes 1
- Anti-β2-glycoprotein-I antibodies (anti-β2GPI) - both IgG and IgM isotypes 1, 2
Testing must be positive on two separate occasions at least 12 weeks apart to fulfill laboratory criteria for antiphospholipid syndrome 1, 5. This repeat testing requirement is critical because transient antibody elevations can occur and do not constitute true APS.
Clinical Implications of Positive Testing
If antiphospholipid antibodies are detected, immediate clinical actions include:
- Consider prophylactic anticoagulation therapy to prevent thrombotic complications during the peripartum period 3
- Recognize increased risk for serious complications: cerebral infarction, pulmonary embolism, deep venous thrombosis, transient monocular blindness, and autoimmune flares 3
- Plan for future pregnancies: Women with confirmed APS require low-dose aspirin (81-100 mg daily) combined with prophylactic-dose LMWH throughout pregnancy 1, 5
- Initiate aspirin prophylaxis early (before 16 weeks, ideally 150 mg/day) for subsequent pregnancies 1
The presence of antiphospholipid antibodies is specifically listed as a risk factor warranting aspirin prophylaxis in the ISSHP 2018 guidelines for preeclampsia prevention 1.
Important Caveats and Pitfalls
Do not routinely screen all women with preeclampsia after 34 weeks - the association between antiphospholipid antibodies and preeclampsia is specific to early-onset disease 2. Testing women with late-onset preeclampsia has low yield unless other clinical features of APS are present 4.
Do not screen for inherited thrombophilias (Factor V Leiden, prothrombin mutation, protein C/S deficiency) in women with preeclampsia or pregnancy complications - this testing is not recommended and does not change management 1. The evidence specifically advises against antithrombotic prophylaxis for inherited thrombophilias with pregnancy complications 1.
Recognize that preeclampsia itself is not sufficient to diagnose APS - while early-onset severe preeclampsia could reasonably be included as a secondary or minor criterion when other clinical features of APS are present, it is not a major diagnostic criterion 4. The diagnosis requires both clinical events (thrombosis or specific obstetric complications) and persistent laboratory evidence 5.
Understand the treatment implications: Approximately 10-17% of pregnancies with established APS develop preeclampsia, and up to 20-30% of women with APS develop complications despite standard treatment with aspirin and LMWH 5. Hydroxychloroquine may provide additional benefit in refractory cases 1, 5.