What is the recommended management for patients with a history of thrombosis or pregnancy complications suspected to be related to antiphospholipid syndrome, including ongoing screening for antiphospholipid antibodies?

Management of Antiphospholipid Syndrome in Patients with History of Thrombosis or Pregnancy Complications

For patients with a history of thrombosis or pregnancy complications suspected to be related to antiphospholipid syndrome (APS), comprehensive laboratory testing for antiphospholipid antibodies (aPL) should be performed, including lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (aβ2GPI), with repeat testing at least 12 weeks apart to confirm persistence of antibodies. 1

Diagnostic Testing Protocol

Initial Evaluation

• Test for all three recommended aPL:
  • Lupus anticoagulant (LAC)
  • β2GPI-dependent anticardiolipin antibodies (aCL) of IgG/IgM isotype
  • Anti-β2-glycoprotein I antibodies (aβ2GPI) of IgG/IgM isotype 1

Confirmation Requirements

• Positive results must be confirmed on two or more occasions at least 12 weeks apart 1
• Antibody levels should be >99th percentile of normal controls for aCL and aβ2GPI 1
• LAC testing should follow Scientific Standardisation Subcommittee recommendations 1

Risk Stratification

• Triple-positive patients (positive for all three aPL tests) are at highest risk for thrombosis or pregnancy complications 1, 2
• Among aPLs, LAC conveys the greatest risk for adverse pregnancy outcomes 1

Management Based on Clinical Presentation

1. Patients with History of Thrombosis (Thrombotic APS)

• Treatment: Long-term anticoagulation with vitamin K antagonists (target INR 2-3) 2
• For pregnant women with thrombotic APS:
  • Switch from vitamin K antagonists to therapeutic-dose LMWH plus low-dose aspirin throughout pregnancy and postpartum 1
  • Avoid direct oral anticoagulants (DOACs), especially in triple-positive patients 2

2. Patients with History of Pregnancy Complications (Obstetric APS)

• Treatment: Combined low-dose aspirin and prophylactic-dose LMWH during pregnancy 1
• Consider adding hydroxychloroquine to the regimen for patients with primary APS 1
• Begin low-dose aspirin early in pregnancy (before 16 weeks) 1
• Continue prophylactic anticoagulation for 6 weeks postpartum 1

3. Asymptomatic aPL-Positive Patients

• For pregnant women with positive aPL who don't meet criteria for APS:
  • Prophylactic aspirin (81-100mg daily) during pregnancy for preeclampsia prevention 1
  • Clinical vigilance rather than routine pharmacologic prophylaxis 1

4. Women with Recurrent Early Pregnancy Loss

• Screen for aPL in women with three or more miscarriages before 10 weeks of gestation 1
• For women with two or more miscarriages but without APLA, antithrombotic prophylaxis is not recommended 1

Special Considerations

Monitoring During Pregnancy

• Monitor aPL-positive pregnancies with:
  • Regular assessment of antiphospholipid antibody levels
  • Platelet count monitoring
  • Surveillance for signs of preeclampsia, intrauterine growth restriction, or placental insufficiency 2
  • For SLE patients, monitor disease activity with clinical history, examination, and laboratory tests at least once per trimester 1

Refractory Obstetric APS

• Standard therapy with low-dose aspirin and prophylactic heparin/LMWH may not prevent all pregnancy losses 1
• Hydroxychloroquine may be beneficial in reducing complications in APS pregnancies 1
• Evidence does not support routine use of intravenous immunoglobulin or increased LMWH doses for cases refractory to standard therapy 1

Pitfalls and Caveats

1. Laboratory Testing Challenges:

   • LAC testing in patients on anticoagulation therapy may produce erroneous results 1
   • Ensure aCL testing is β2GPI-dependent to avoid detection of non-cofactor-related aCL associated with infections or drugs 1

2. Treatment Considerations:

   • Heparin dosing during pregnancy differs from non-pregnant patients due to altered pharmacokinetics 3
   • Activated partial thromboplastin time (aPTT) is not reliable for monitoring heparin therapy in pregnancy, especially with lupus anticoagulant present 3

3. Contraception:

   • Oral contraceptives containing estrogens should generally be avoided in women with APS due to increased thrombotic risk 4, 5
   • Barrier methods, intrauterine devices (if not on corticosteroids), or progestin-only options are preferred 4

By following these evidence-based recommendations, clinicians can optimize outcomes for patients with suspected or confirmed antiphospholipid syndrome, reducing the risk of recurrent thrombosis and pregnancy complications.