What is the primary treatment for Antiphospholipid Antibody Syndrome (APAS)?

Treatment of Antiphospholipid Antibody Syndrome (APAS)

The primary treatment for APAS depends critically on clinical presentation: for thrombotic APS, long-term warfarin with target INR 2.0-3.0 is the cornerstone; for obstetric APS, combined low-dose aspirin (81-100 mg daily) plus prophylactic-dose LMWH is strongly recommended; and for asymptomatic antiphospholipid antibody-positive patients, prophylactic aspirin alone is conditionally recommended. 1, 2, 3

Treatment Algorithm by Clinical Scenario

Thrombotic APS (History of Venous or Arterial Thrombosis)

For venous thrombosis:

• Warfarin with target INR 2.5 (range 2.0-3.0) is the gold standard for long-term anticoagulation 2, 3, 4
• Duration is typically indefinite given persistent antibody presence and ongoing thrombotic risk 3, 4, 5
• Direct oral anticoagulants (DOACs) must be avoided, especially in triple-positive patients, due to significantly increased risk of recurrent thrombotic events including stroke 2, 3, 6

For arterial thrombosis:

• Warfarin with target INR 2.5 (range 2.0-3.0) plus low-dose aspirin (75-100 mg daily) 2, 3
• Some guidelines suggest considering higher intensity anticoagulation (INR 3.0-4.0) for arterial events 3, 7
• Aspirin monotherapy is insufficient for arterial thrombosis in APS 3

Obstetric APS (Recurrent Pregnancy Loss or Pregnancy Complications)

Standard therapy during pregnancy:

• Combined low-dose aspirin (81-100 mg daily) AND prophylactic-dose heparin (usually LMWH) is strongly recommended 1, 2
• Start aspirin before 16 weeks gestation and continue through delivery 1
• Continue prophylactic-dose anticoagulation for 6-12 weeks postpartum 1

Adjunctive therapy:

• Hydroxychloroquine may be conditionally added to standard therapy for patients with primary APS, as recent studies suggest decreased complications 1, 2, 3

Important caveat: Despite optimal treatment, pregnancy loss still occurs in 25% of obstetric APS pregnancies 1

Pregnant Women with Thrombotic APS

This is the highest-risk scenario requiring aggressive treatment:

• Low-dose aspirin (81-100 mg daily) PLUS therapeutic-dose heparin (usually LMWH) throughout pregnancy and postpartum 1, 2
• Warfarin is absolutely contraindicated during pregnancy due to teratogenicity 3

Asymptomatic Antiphospholipid Antibody-Positive Patients

Without history of thrombosis or pregnancy complications:

• Prophylactic aspirin (81-100 mg daily) is conditionally recommended during pregnancy as preeclampsia prophylaxis, starting before 16 weeks 1
• For non-pregnant patients with high-risk antibody profiles (triple-positive, double-positive with LAC, or persistently high titers), low-dose aspirin (75-100 mg daily) for primary prevention 2, 3, 6
• Do not use prophylactic heparin plus aspirin in patients who don't meet APS criteria unless high-risk features present (triple-positive aPL, strongly positive LAC, advanced maternal age, or IVF pregnancy) 1

Critical Risk Stratification

High-risk antibody profiles requiring more aggressive management: 2, 3, 6

• Triple-positive (LAC + aCL + aβ2GPI): highest thrombotic risk
• Double-positive with LAC present
• Isolated LAC positivity (conveys greatest risk among single antibodies)
• Persistently high-titer anticardiolipin (≥80 Units) or anti-β2GPI antibodies

Low-risk profiles:

• Isolated anticardiolipin or anti-β2GPI at low-medium titers (<40 Units)

Refractory APS Management

For patients failing standard therapy:

Strongly recommended AGAINST: 1

• Adding prednisone to standard therapy (no controlled studies showing benefit, significant potential harm)
• Increasing LMWH dose (no data demonstrating improved outcomes)
• Intravenous immunoglobulin (only anecdotal support, not demonstrably helpful)

May consider in select refractory cases:

• Hydroxychloroquine as adjunctive therapy 2, 3, 8
• Increasing target INR range for warfarin 2
• For catastrophic APS: aggressive triple therapy with anticoagulation, glucocorticoids, and plasma exchange 2, 6, 7

Common Pitfalls and Critical Caveats

Never use DOACs in APS patients, particularly triple-positive patients - this is associated with excess thrombotic events compared to warfarin, especially arterial thrombosis and stroke 2, 3, 6. If a patient is already on a DOAC, transition to warfarin immediately 2.

Do not discontinue anticoagulation prematurely - antiphospholipid antibodies typically persist and thrombotic risk remains elevated, requiring indefinite anticoagulation in most cases 3, 4, 5.

Avoid estrogen-containing contraceptives in women with positive antiphospholipid antibodies due to significantly increased thrombosis risk; use intrauterine devices or progestin-only pills instead 6.

Thrombocytopenia does not reduce thrombotic risk in APS - patients can develop thromboembolic complications despite low platelet counts, and anticoagulation should not be withheld based on thrombocytopenia alone unless critically low or active bleeding present 2, 9.

INR monitoring may be unreliable during sepsis due to hepatic dysfunction and consumptive coagulopathy, but therapeutic anticoagulation should be continued unless active bleeding or specific contraindication exists 2.

Confirm antibody persistence - diagnosis requires positive antibodies on two occasions at least 12 weeks apart; a single positive test is insufficient 2, 3, 6.