Antiphospholipid Syndrome

Jacob Lee

Background

  • Antiphospholipid antibodies (aPL – includes lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein-1 (anti- β 2GP1)) target phospholipid-binding proteins which are present in every tissue bed.
  • Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity or non-thrombotic manifestations in patients with persistent aPL.

Diagnostic Criteria

  • At least one documented clinical criterion:
    • Macrovascular (VTE, arterial thrombosis).
    • Microvascular (livedo racemosa/vasculopathy, nephropathy, pulmonary or adrenal hemorrhage, myocardial disease).
    • Obstetric (fetal death, pre-eclampsia, placental insufficiency).
    • Heart valve thickening/vegetation.
  • Hematologic manifestations: thrombocytopenia
  • PLUS a positive antiphospholipid antibody test within three years of clinical criteria.
  • Positive: LAC or moderate-to-high titer of aCL or anti-β2GP1.
  • ACR has a scoring criteria that applies different weights across the clinical and laboratory domains.

Management

  • Primary prevention of thrombosis: consider aspirin in patients with high risk aPL profiles (positive LAC with or without others, aCL or anti-β2GP1) and low bleeding risk.
  • Thrombosis: indefinite anticoagulation, where VKA is preferred to DOAC.
  • VTE: VKA with INR 2-3.
  • Arterial thrombosis: Either VKA w/ INR 2-3 plus aspirin OR VKA monotherapy with INR 3-4.
  • Do NOT use DOACs for triple positive APLS (TRAPS trial).
  • Hydroxychloroquine reduces thrombosis risk in SLE-associated APS.

Strategies for Recurrent Thromboses

  • Switching to LMWH at therapeutic doses.
  • Adding low dose ASA, HCQ, statins.
  • Immunosuppression (Rituximab) for severe, refractory cases.
  • Increase INR goal to 3-4 (data suggests this is not helpful and may even be harmful).
  • Microvascular complications: occasionally treated with steroids / immunomodulation based off of severity; limited benefit and often refractory to AC.
  • Obstetric: combination of low dose aspirin and prophylactic-dose heparin during pregnancy until 6 weeks postpartum.
    • Monthly US with doppler.
  • Statins: considered in arterial APS for endothelial protection.

Catastrophic APS (CAPS)

Diagnostic Criteria:

  • Multiple (≥3) organs/tissues involved with MICROvascular clots.
    Rapid (<1 week) onset
  • Histopathologic confirmation of small vessel occlusion in at least one organ/tissue Laboratory
    confirmation of aPL antibodies (detected on 2 occasions 12 weeks apart)
  • All 4 criteria met: Definite CAPS; probable CAPS is diagnosed when some but not all 4 criteria met (see guidelines for specifics)
    • Common Sites: kidneys (renal failure, hypertension), lungs (ARDS, DAH, pulmonary embolism), brain (stroke, seizures, encephalopathy), heart (myocardial infarction, valve thrombosis), skin (livedo reticularis, purpura, necrosis), adrenals (adrenal insufficiency).
    • Often mimics sepsis with fevers and elevated inflammatory markers.
  • Triggers: Identified in ~50% of cases—e.g., infection (most common), surgery, trauma, pregnancy, or anticoagulation withdrawal.

Management:

  • IV heparin and high dose steroids
  • For refractory cases: consider PLEX, IVIG (if planning to do both PLEX and IVIG, start with PLEX), rituximab (limited role, refractory cases).
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