How is Antiphospholipid Syndrome (APS) typically treated?

Treatment of Antiphospholipid Syndrome (APS)

Treatment of APS depends critically on whether the patient has experienced thrombotic events, pregnancy complications, or remains asymptomatic with positive antibodies—with vitamin K antagonists (warfarin) as the gold standard for thrombotic APS and combined aspirin plus heparin for obstetric APS. 1

Asymptomatic Antiphospholipid Antibody-Positive Patients

For patients with positive antiphospholipid antibodies but no history of thrombosis or pregnancy complications:

• Low-dose aspirin (75-100 mg daily) is recommended for primary prevention in patients with high-risk antibody profiles (triple-positive, double-positive, isolated lupus anticoagulant, or persistently positive anticardiolipin at medium-to-high titers) 2
• High-risk profiles include lupus anticoagulant positivity, double or triple antibody positivity, or persistently high antibody titers (>40 GPL or MPL units, or >99th percentile) 2, 1
• Low-risk profiles (isolated anticardiolipin or anti-β2-glycoprotein 1 at low-medium titers, especially if transient) may be considered for aspirin prophylaxis after risk-benefit evaluation 2
• Asymptomatic patients are not treated with anticoagulation—aspirin alone suffices for primary prevention 2, 1

Thrombotic APS (Non-Pregnant Patients)

For patients with venous thrombosis and confirmed APS, long-term anticoagulation with warfarin targeting INR 2.0-3.0 is strongly recommended and represents the standard of care. 1, 3, 4

Venous Thrombosis Management:

• Warfarin with target INR 2.5 (range 2.0-3.0) for indefinite duration 1, 3
• For first episode with transient risk factor: minimum 3 months 3
• For idiopathic first episode: at least 6-12 months, with indefinite therapy suggested 3
• For recurrent thrombosis or high-risk antibody profiles: indefinite anticoagulation 3, 4

Arterial Thrombosis Management:

• Warfarin with target INR 2.0-3.0 is recommended, though higher intensity (INR 3.0-4.0) may be considered for arterial events 1
• For APS with prior unprovoked venous thrombosis, vitamin K antagonist therapy (INR 2.0-3.0) is reasonable over aspirin or direct oral anticoagulants 2

Critical Caveat - Avoid DOACs:

• Direct oral anticoagulants (DOACs) should be avoided in APS patients, especially those with triple-positive antibodies, due to increased risk of recurrent arterial thrombosis compared to warfarin 1, 4, 5
• If a triple-positive patient is already on a DOAC, transition to warfarin immediately 1

Obstetric APS (Pregnant Patients)

Pregnant Women with Positive aPL (Not Meeting Full APS Criteria):

• Prophylactic aspirin (81-100 mg daily) starting before 16 weeks and continuing through delivery is conditionally recommended for preeclampsia prophylaxis 2, 1
• Prophylactic heparin is not routinely recommended unless additional high-risk features exist (triple-positive, advanced maternal age, IVF pregnancy) 2, 1

Obstetric APS (Meeting Criteria):

• Combined low-dose aspirin (81-100 mg daily) plus prophylactic-dose LMWH throughout pregnancy is strongly recommended 2, 1
• Treatment should begin early (before 16 weeks gestation) 2
• Continue through delivery and postpartum period 2

Thrombotic APS During Pregnancy:

• Low-dose aspirin plus therapeutic-dose LMWH throughout pregnancy and postpartum is strongly recommended 2, 1
• This represents the highest-risk pregnancy scenario requiring the most intensive anticoagulation 1

Adjunctive Therapy:

• Hydroxychloroquine may be added to standard therapy (aspirin + LMWH) for patients with primary APS, as recent studies suggest it decreases pregnancy complications 2, 1
• This is a conditional recommendation based on emerging evidence 2

Refractory or High-Risk APS

For patients who fail standard therapy or have catastrophic APS:

• Consider increasing warfarin target INR range (to 3.0-4.0) for refractory cases 1
• Hydroxychloroquine as adjunctive therapy is recommended for refractory APS 1, 6
• For catastrophic APS: aggressive combination therapy with anticoagulation, high-dose glucocorticoids, plasma exchange, and intravenous immunoglobulins 1, 6
• If catastrophic APS occurs with SLE flare, add intravenous cyclophosphamide (500-1000 mg/m² monthly) 1

Special Populations and Situations

APS with Systemic Lupus Erythematosus:

• Prophylactic aspirin (75-100 mg daily) is recommended for SLE patients with high-risk aPL profiles even without prior thrombosis 2
• Hydroxychloroquine should be continued throughout pregnancy in SLE patients 2

APS with Thrombocytopenia:

• Thrombocytopenia does not reduce thrombotic risk in APS patients—anticoagulation remains necessary despite low platelet counts 7
• Treatment of thrombocytopenia may be required to facilitate safe anticoagulation 7
• Do not withhold anticoagulation based on thrombocytopenia alone unless platelets are critically low or active bleeding exists 1

Assisted Reproductive Technology (ART):

• For obstetric APS undergoing ART: prophylactic LMWH starting at ovarian stimulation, withheld 24-36 hours before oocyte retrieval, resumed after retrieval 1
• For thrombotic APS undergoing ART: therapeutic anticoagulation throughout 1

Monitoring and Duration

• INR monitoring is essential for warfarin therapy, targeting 2.5 (range 2.0-3.0) for most patients 3
• Reassess risk-benefit periodically for patients on indefinite anticoagulation 3
• Triple-positive patients and those with lupus anticoagulant require more intensive monitoring due to highest thrombotic risk 1, 4
• Postpartum anticoagulation should continue for minimum 6-12 weeks, with total duration of at least 3 months from delivery 1

Common Pitfalls to Avoid

• Never use DOACs in triple-positive APS—this significantly increases arterial thrombosis risk 1, 5
• Do not stop anticoagulation in APS patients with sepsis unless active bleeding or specific contraindication exists—sepsis itself is prothrombotic and synergizes with APS thrombotic risk 1
• Avoid warfarin during pregnancy due to teratogenicity—use LMWH instead 1
• Do not delay aspirin initiation in pregnancy—must start before 16 weeks for preeclampsia prevention 2, 1
• Large loading doses of warfarin increase hemorrhagic complications without faster protection—start with 2-5 mg daily 3