Antiphospholipid Syndrome

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.

⭐ "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

⭐ 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.