Related Subjects: Thrombophilia testing
|Antiphospholipid syndrome
|Protein C Deficiency
|Protein S Deficiency
|Prothrombin 20210A mutation
|Factor V Leiden Deficiency
|Antithrombin III deficiency (AT3)
|Cerebral Venous Sinus thrombosis
|Budd-Chiari syndrome
🩸 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
| Type | Description |
|---|
| Primary APS | APS without underlying disease. |
| Secondary APS | APS associated with another disease (esp. SLE). |
👩⚕️ 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.
| Clinical Criteria |
|---|
- Vascular thrombosis (arterial, venous, small vessel).
- Pregnancy morbidity:
- ≥1 unexplained fetal death ≥10 weeks.
- ≥1 premature birth <34 weeks due to eclampsia/pre-eclampsia/placental insufficiency.
- ≥3 consecutive miscarriages <10 weeks.
|
| Laboratory Criteria |
|---|
- Lupus anticoagulant (LA).
- Anticardiolipin antibody (IgG/IgM, >40GPL/MPL or >99th percentile).
- Anti-β2-glycoprotein-1 antibody (IgG/IgM, >99th percentile).
|
📈 Global Antiphospholipid Syndrome Score (GAPSS)
- Predicts risk of thrombosis/pregnancy loss by combining antibody profile + CV risk factors.
| GAPSS Points |
|---|
- aCL antibodies: 5
- Anti-β2GP1 antibodies: 4
- Lupus anticoagulant: 4
- Anti-prothrombin/phosphatidylserine: 3
- Hyperlipidaemia: 3
- Hypertension: 1
|
🔬 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
Cases - Antiphospholipid Syndrome (APS)
- Case 1 - Venous thrombosis 🦵: A 29-year-old woman presents with left leg swelling and pain. Doppler ultrasound: proximal DVT. She reports two previous miscarriages at 12 and 14 weeks. Blood tests: positive lupus anticoagulant on two occasions 12 weeks apart. Diagnosis: antiphospholipid syndrome with recurrent pregnancy loss and venous thrombosis. Managed with anticoagulation (warfarin) and future pregnancy planning with aspirin + LMWH.
- Case 2 - Arterial thrombosis 🧠: A 41-year-old man presents with sudden right-sided weakness and dysphasia. CT head: ischaemic stroke. No vascular risk factors. Bloods: persistently positive anticardiolipin antibody. Diagnosis: APS presenting with arterial stroke. Managed with long-term anticoagulation.
- Case 3 - Catastrophic APS ⚡: A 36-year-old woman develops multi-organ failure over 48 hours following infection: renal failure, ARDS, and digital ischaemia. Coagulation screen: consumptive coagulopathy. Diagnosis: catastrophic APS. Managed in ITU with anticoagulation, IV steroids, plasma exchange, and rituximab under haematology input.
Teaching Point 🩺: APS is an autoimmune hypercoagulable state caused by antibodies (anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein I). It causes both venous and arterial thromboses, recurrent pregnancy loss, and rarely catastrophic APS. Always confirm with repeat antibody positivity ≥12 weeks apart.
