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
๐ฉธ 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 โ paradox: โ clotting in vivo, but prolonged clotting tests in vitro.
โน๏ธ About
- Primary (idiopathic) or secondary (e.g. SLE, CTD, HIV, Hep C, lymphoproliferative disease).
- Female > Male (โ2โ3:1).
- Antiphospholipid antibodies in 1โ5% of population, โ with age.
- Transient positivity common after infections โ repeat testing โฅ12 weeks apart required.
๐งช The Big 3 Antibodies
- ๐ต Lupus anticoagulant (LA) โ strongest risk for thrombosis.
- ๐ Anticardiolipin antibodies (aCL) โ IgG/IgM detected via ELISA.
- ๐ข Anti-ฮฒ2 glycoprotein-1 antibodies โ classical hallmark, IgG/IgM isotypes.
โ๏ธ Aetiology & Pathophysiology
- Autoantibody binds ฮฒ2-glycoprotein-1 on phospholipids โ loss of anticoagulant activity.
- Endothelial dysfunction, platelet activation, complement activation โ thrombosis.
- In vitro: prolonged APTT (lab artefact).
In vivo: paradoxical hypercoagulability โ arterial & venous clots.
๐ Classification
| Type | Description |
|---|
| Primary APS | APS without underlying disease. |
| Secondary APS | APS associated with another disease (esp. SLE). |
๐ฉโโ๏ธ Clinical Features
- ๐ด Thrombosis
- Venous: DVT, PE, cerebral venous sinus thrombosis, BuddโChiari.
- Arterial: Stroke/TIA, MI, limb ischaemia.
- Catastrophic APS (CAPS): multiple clots in short time โ multiorgan failure.
- ๐คฐ Pregnancy morbidity: โฅ3 miscarriages, IUFD >10 weeks, preterm delivery due to placental insufficiency, severe pre-eclampsia.
- ๐ฉบ Other: thrombocytopenia, migraines, livedo reticularis (knees), valvular disease (Libman-Sacks endocarditis), adrenal infarction, renal artery stenosis.
๐งพ Revised Classification Criteria (2006)
Diagnosis requires at least 1 clinical AND 1 laboratory criterion, repeated โฅ12 weeks apart.
| Clinical Criteria |
|---|
- Vascular thrombosis (arterial, venous, small vessel).
- Pregnancy morbidity:
- โฅ1 unexplained fetal death โฅ10 weeks.
- โฅ1 premature birth <34 weeks due to eclampsia/pre-eclampsia/placental insufficiency.
- โฅ3 consecutive miscarriages <10 weeks.
|
| Laboratory Criteria |
|---|
- Lupus anticoagulant (LA).
- Anticardiolipin antibody (IgG/IgM, >40GPL/MPL or >99th percentile).
- Anti-ฮฒ2-glycoprotein-1 antibody (IgG/IgM, >99th percentile).
|
๐ Global Antiphospholipid Syndrome Score (GAPSS)
- Predicts risk of thrombosis/pregnancy loss by combining antibody profile + CV risk factors.
| GAPSS Points |
|---|
- aCL antibodies: 5
- Anti-ฮฒ2GP1 antibodies: 4
- Lupus anticoagulant: 4
- Anti-prothrombin/phosphatidylserine: 3
- Hyperlipidaemia: 3
- Hypertension: 1
|
๐ฌ 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 โฅ12 weeks for persistence).
- Echo (esp. TEE) in stroke patients โ valvular vegetations common.
- Exclude false positives (e.g. syphilis serology).
๐ Differentials
- Vasculitis (esp. SLE).
- Other thrombophilias (Factor V Leiden, Protein C/S deficiency).
- Atrial myxoma.
- DIC / TTP.
๐ Management
- ๐ First thrombosis: Long-term warfarin (INR 2โ3; higher target if recurrent arterial).
- ๐งด Low-dose aspirin (75mg) ยฑ hydroxychloroquine in low-risk or primary prevention.
- ๐คฐ In pregnancy: LMWH + aspirin; avoid warfarin (teratogenic).
- โ DOACs not recommended (higher recurrence risk in APS).
- CAPS: high-dose steroids + anticoagulation + plasma exchange ยฑ rituximab.
- Always involve haematology specialist.
๐ References
Cases โ Antiphospholipid Syndrome (APS)
- Case 1 โ Venous thrombosis ๐ฆต: 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 โ Arterial thrombosis ๐ง : 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 โ Catastrophic APS โก: 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 ๐ฉบ: APS is an autoimmune hypercoagulable state caused by antibodies (anticardiolipin, lupus anticoagulant, anti-ฮฒ2 glycoprotein I). It causes both venous and arterial thromboses, recurrent pregnancy loss, and rarely catastrophic APS. Always confirm with repeat antibody positivity โฅ12 weeks apart.
