Antiphospholipid Syndrome

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APS: Definition & Pathophysiology - Clotty Blood Woes

  • Systemic autoimmune disorder defined by persistent antiphospholipid antibodies (aPL), leading to:
    • Recurrent arterial or venous thrombosis.
    • Pregnancy morbidity (e.g., recurrent fetal loss, preeclampsia, placental insufficiency).
  • Key pathogenic aPLs target phospholipid-binding proteins, primarily β2-glycoprotein I:
    • Lupus Anticoagulant (LA)
    • Anti-cardiolipin (aCL) antibodies (IgG/IgM)
    • Anti-β2 glycoprotein I (anti-β2GPI) antibodies (IgG/IgM)
  • Pathophysiology: aPLs induce a prothrombotic state via:
    • Endothelial cell activation & dysfunction (↑tissue factor, ↓protein C).
    • Platelet activation & aggregation.
    • Complement system activation.
    • Impaired trophoblast function & placental development. Antiphospholipid Syndrome Pathogenesis

⭐ "Catastrophic APS" (CAPS) is a rare, life-threatening variant characterized by widespread microthrombosis affecting multiple organs, often triggered by infection or surgery.

APS: Clinical Manifestations - Symptoms & Signs

  • Vascular Thrombosis (Arterial or Venous)
    • Deep Vein Thrombosis (DVT) - most common
    • Pulmonary Embolism (PE)
    • Stroke / Transient Ischemic Attack (TIA)
    • Myocardial Infarction (MI)
    • Peripheral arterial occlusion
    • Recurrent events are common
  • Pregnancy Morbidity
    • 3 unexplained consecutive spontaneous abortions <10 weeks gestation
    • 1 unexplained fetal death ≥10 weeks gestation (morphologically normal fetus)
    • 1 premature birth ≤34 weeks due to eclampsia, pre-eclampsia, or placental insufficiency
  • Other Features
    • Livedo reticularis / racemosa
    • Thrombocytopenia (mild to moderate)
    • Valvular heart disease (Libman-Sacks endocarditis)
    • Nephropathy
    • Neurological: chorea, migraine, seizures

Livedo reticularis on legs

⭐ Catastrophic Antiphospholipid Syndrome (CAPS) is a rare, life-threatening variant with widespread microthrombosis affecting multiple organs simultaneously or within a week; high mortality despite aggressive therapy (often <1% of APS patients).

APS: Diagnosis - Pinpointing APS

Diagnosis hinges on the Revised Sapporo (Sydney) Criteria:

  • Requires ≥1 Clinical AND ≥1 Laboratory Criterion.
  • Lab criteria persistent: ≥2 positive tests, ≥12 weeks apart.

Clinical Criteria (Need ≥1):

  • Vascular Thrombosis: ≥1 episode (arterial, venous, or small vessel).
  • Pregnancy Morbidity: (select one)
    • 1 unexplained fetal death (normal fetus) ≥10 weeks gestation.
    • 1 premature birth (normal neonate) <34 weeks due to eclampsia/severe preeclampsia/placental insufficiency.
    • 3 unexplained consecutive spontaneous abortions <10 weeks gestation.

Laboratory Criteria (Need ≥1, persistent):

  • Lupus Anticoagulant (LA): Detected in plasma.
  • aCL Ab (IgG/IgM): Medium/high titre (>40 GPL/MPL or >99th %ile).
  • Anti-β2GPI Ab (IgG/IgM): Titre >99th %ile.

⭐ Lupus anticoagulant (LA) is the strongest predictor of thrombosis and pregnancy morbidity in APS.

APS: Management - Treating the Clots

  • Acute Thrombotic Event:
    • Initial: LMWH (Enoxaparin 1 mg/kg BD) or IV UFH (aPTT guided).
    • Transition to Warfarin:
      • Start Warfarin; INR 2.0-3.0 (VTE), consider >3.0 (arterial/recurrent).
      • Bridge LMWH/UFH ≥5 days & therapeutic INR 24-48h.
  • Long-term Anticoagulation (Secondary Prophylaxis):
    • Warfarin: Lifelong standard. Target INR 2.0-3.0 (VTE); 3.0-4.0 for high-risk (e.g., recurrent arterial thrombosis).
    • ⚠️ DOACs: Generally NOT first-line. Avoid in triple-positive APS or arterial thrombosis due to ↑ recurrence risk.
  • Catastrophic APS (CAPS):
    • Aggressive combination:
      • Anticoagulation (UFH).
      • High-dose Glucocorticoids.
      • PLEX or IVIG.
      • Refractory: Consider Rituximab, Eculizumab.

⭐ For APS patients with recurrent arterial thrombosis on warfarin (INR 2-3), options include increasing INR target to 3.0-4.0 or adding low-dose aspirin.

High‑Yield Points - ⚡ Biggest Takeaways

  • APS is an autoimmune disorder characterized by recurrent thrombosis (arterial or venous) and/or pregnancy morbidity.
  • Key antibodies include Lupus Anticoagulant (LA), anti-Cardiolipin (aCL) antibodies, and anti-β2 Glycoprotein I (anti-β2GPI) antibodies.
  • Diagnosis requires at least one clinical criterion and persistent laboratory evidence of aPL antibodies (confirmed on ≥2 occasions, at least 12 weeks apart).
  • Treatment for thrombotic APS involves lifelong anticoagulation (e.g., warfarin); aspirin + heparin/LMWH is used during pregnancy.
  • Catastrophic APS (CAPS) is a rare, life-threatening variant with widespread microvascular thrombosis and multi-organ failure.
  • Frequently associated with Systemic Lupus Erythematosus (SLE); may present with livedo reticularis or thrombocytopenia.

Practice Questions: Antiphospholipid Syndrome

Test your understanding with these related questions

Which of the following conditions is not associated with antiphospholipid syndrome?

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Flashcards: Antiphospholipid Syndrome

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What antibodies are antiphospholipid antibodies? _____, lupus anticoagulant, and anti-2 glycoprotein

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What antibodies are antiphospholipid antibodies? _____, lupus anticoagulant, and anti-2 glycoprotein

Anti-cardiolipin

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