Makindo Medical Notes

🩸 Antiphospholipid Syndrome (APS) is an autoimmune prothrombotic condition with vascular thrombosis and pregnancy morbidity. Also called Hughes syndrome. Caused by autoantibodies against phospholipid-binding proteins → paradox: ↑ clotting in vivo, but prolonged clotting tests in vitro.

ℹ️ About

• Primary (idiopathic) or secondary (e.g. SLE, CTD, HIV, Hep C, lymphoproliferative disease).
• Female > Male (≈2–3:1).
• Antiphospholipid antibodies in 1–5% of population, ↑ with age.
• Transient positivity common after infections → repeat testing ≥12 weeks apart required.

🧪 The Big 3 Antibodies

• 🔵 Lupus anticoagulant (LA) – strongest risk for thrombosis.
• 🟠 Anticardiolipin antibodies (aCL) – IgG/IgM detected via ELISA.
• 🟢 Anti-β2 glycoprotein-1 antibodies – classical hallmark, IgG/IgM isotypes.

⚙️ Aetiology & Pathophysiology

• Autoantibody binds β2-glycoprotein-1 on phospholipids → loss of anticoagulant activity.
• Endothelial dysfunction, platelet activation, complement activation → thrombosis.
• In vitro: prolonged APTT (lab artefact). In vivo: paradoxical hypercoagulability → arterial & venous clots.

📊 Classification

👩‍⚕️ Clinical Features

• 🔴 Thrombosis
  • Venous: DVT, PE, cerebral venous sinus thrombosis, Budd–Chiari.
  • Arterial: Stroke/TIA, MI, limb ischaemia.
  • Catastrophic APS (CAPS): multiple clots in short time → multiorgan failure.
• 🤰 Pregnancy morbidity: ≥3 miscarriages, IUFD >10 weeks, preterm delivery due to placental insufficiency, severe pre-eclampsia.
• 🩺 Other: thrombocytopenia, migraines, livedo reticularis (knees), valvular disease (Libman-Sacks endocarditis), adrenal infarction, renal artery stenosis.

🧾 Revised Classification Criteria (2006)

Diagnosis requires at least 1 clinical AND 1 laboratory criterion, repeated ≥12 weeks apart.

📈 Global Antiphospholipid Syndrome Score (GAPSS)

• Predicts risk of thrombosis/pregnancy loss by combining antibody profile + CV risk factors.

🔬 Investigations

• FBC: thrombocytopenia, haemolysis (Coombs+).
• Coagulation: prolonged APTT not corrected by normal plasma; dilute Russell viper venom test prolonged.
• ESR/CRP often normal (helps exclude vasculitis).
• Antibody assays (repeat after ≥12 weeks for persistence).
• Echo (esp. TEE) in stroke patients → valvular vegetations common.
• Exclude false positives (e.g. syphilis serology).

🔍 Differentials

• Vasculitis (esp. SLE).
• Other thrombophilias (Factor V Leiden, Protein C/S deficiency).
• Atrial myxoma.
• DIC / TTP.

💊 Management

• 💉 First thrombosis: Long-term warfarin (INR 2–3; higher target if recurrent arterial).
• 🧴 Low-dose aspirin (75mg) ± hydroxychloroquine in low-risk or primary prevention.
• 🤰 In pregnancy: LMWH + aspirin; avoid warfarin (teratogenic).
• ❌ DOACs not recommended (higher recurrence risk in APS).
• CAPS: high-dose steroids + anticoagulation + plasma exchange ± rituximab.
• Always involve haematology specialist.

📚 References

• Miyakis S, Lockshin MD, Atsumi T, et al. J Thromb Haemost. 2006.
• Cochrane Review: Antiplatelet & anticoagulant agents in APS.
• APS & Stroke in Young Women.
• Risk of ischaemic stroke in primary APS.