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Antiphospholipid Syndrome

Last updated 31 May 2026 · Haematology clinical guideline

📋 Key Information Summary

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  • Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia with persistent antiphospholipid antibodies (aPL).
  • The three main pathogenic antibodies are lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-B2GP1).
  • Clinical hallmarks are vascular thrombosis (arterial, venous, small-vessel) and specific pregnancy morbidity.
  • Diagnosis requires at least one clinical criterion and one laboratory criterion, with antibodies positive on two occasions ≥12 weeks apart (Sapporo/Sydney criteria).
  • First-line long-term therapy for thrombotic APS is warfarin (target INR 2.0–3.0 for venous; may target 2.5–3.5 for arterial).
  • Direct oral anticoagulants (DOACs) are generally inferior to warfarin in APS, especially in triple-positive patients, and are not recommended first-line.
  • For obstetric APS, treatment is with low-dose aspirin (LDA) ± prophylactic LMWH, which significantly improves live birth rates.
  • Hydroxychloroquine (HCQ) is a key immunomodulator, particularly in APS associated with SLE, and may reduce thrombotic risk.
  • Catastrophic APS (CAPS) is a rare, life-threatening emergency requiring anticoagulation, high-dose corticosteroids, and often plasma exchange or IVIG.
  • Aboriginal and Torres Strait Islander patients may have higher prevalence of autoimmune conditions and face barriers to specialist access and anticoagulation monitoring.
Antiphospholipid Syndrome clinical infographic — pathophysiology, clinical clues, diagnosis, imaging, and management
Tap or click image to enlarge — Antiphospholipid Syndrome: pathophysiology, clinical clues, diagnosis, imaging, and management.
Antiphospholipid Syndrome infographic, full size

Introduction & Australian Epidemiology

Antiphospholipid syndrome (APS) is an acquired thrombophilia characterised by arterial or venous thrombosis and specific pregnancy complications, associated with persistent autoantibodies directed against phospholipid-binding proteins. It is a major cause of acquired thrombosis and recurrent pregnancy loss.

In Australia, APS affects an estimated 40–50 per 100,000 population. It is the most common acquired risk factor for venous thromboembolism (VTE) in younger patients (<50 years) and a significant cause of stroke in the absence of traditional vascular risk factors. The prevalence of antiphospholipid antibodies in the general population is about 1–5%, but only a subset develops clinical APS. It is more common in women, particularly obstetric APS, and has a strong association with systemic lupus erythematosus (SLE).

Pathogenesis & Antibodies

APS is driven by a heterogeneous group of autoantibodies targeting phospholipid-binding proteins. The pathogenesis involves a "two-hit" hypothesis: antibodies create a prothrombotic state, with a second trigger (e.g., surgery, infection, oestrogen) precipitating thrombosis.

Key Pathogenic Antibodies

  • Lupus Anticoagulant (LA): An in vitro phenomenon prolonging phospholipid-dependent coagulation tests (e.g., dRVVT, APTT). Despite the name, it is strongly associated with in vivo thrombosis. It is considered the strongest risk marker for thrombosis and pregnancy complications.
  • Anticardiolipin Antibodies (aCL): Detected by ELISA. IgG and IgM isotypes are considered. High titres (>40 GPL/MPL or >99th percentile) are clinically significant.
  • Anti-β2-glycoprotein I Antibodies (anti-β2GPI): Detected by ELISA. Considered more specific for APS than aCL. IgG and IgM isotypes are relevant.
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Risk Stratification: "Triple positivity" (LA + aCL + anti-β2GPI) confers the highest risk of thrombosis and pregnancy morbidity. Isolated aCL or anti-β2GPI positivity, especially at low titres, carries lower risk.

Clinical Features

Thrombosis

Thrombosis can be venous, arterial, or small-vessel, and may occur in any vascular bed.

  • Venous: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are most common. Unusual site thrombosis (e.g., cerebral venous sinus, hepatic, portal, renal veins) is a clue.
  • Arterial: Ischaemic stroke and transient ischaemic attack (TIA) are the most frequent arterial events. Myocardial infarction, peripheral arterial occlusion, and retinal artery occlusion also occur.
  • Small-vessel: Livedo reticularis/racemosa, renal thrombotic microangiopathy, adrenal haemorrhage.

Pregnancy Morbidity

APS is a treatable cause of recurrent pregnancy loss.

  • ≥1 unexplained death of a morphologically normal foetus at or beyond 10 weeks' gestation.
  • ≥1 premature birth before 34 weeks due to severe pre-eclampsia or placental insufficiency.
  • ≥3 unexplained consecutive spontaneous abortions before 10 weeks.

Other Manifestations

  • Cardiac: Libman-Sacks endocarditis, valvular thickening.
  • Haematological: Thrombocytopenia, haemolytic anaemia.
  • Neurological: Cognitive dysfunction, seizures, chorea.
  • Catastrophic APS (CAPS): Rapid-onset multi-organ thrombosis with microangiopathy (3+ organs in <1 week). Mortality ~30–50%.

Sapporo Criteria & Investigations

Diagnosis is based on the 2006 Sydney revised Sapporo classification criteria. At least one clinical and one laboratory criterion must be met.

Clinical Criteria

  1. Vascular thrombosis: One or more episodes of arterial, venous, or small-vessel thrombosis in any tissue/organ, confirmed by objective validated criteria.
  2. Pregnancy morbidity: As detailed above.

Laboratory Criteria

Must be present on two or more occasions at least 12 weeks apart.

  1. Lupus anticoagulant (LA) present in plasma.
  2. Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in serum or plasma, present in medium or high titre (>40 GPL/MPL or >99th percentile).
  3. Anti-β2-glycoprotein I antibody (anti-β2GPI) of IgG and/or IgM isotype in serum or plasma (in titre >99th percentile).
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Critical Rule: A positive test must be confirmed ≥12 weeks later. Transient antibodies can occur with infection, drugs, or other illness and do not constitute APS.

Key Investigations (Australian Context)

MBS Available
Lupus Anticoagulant (LA) Panel
Includes dRVVT, APTT (LA-sensitive), mixing studies, phospholipid correction. MBS Item 71114. Performed in major pathology labs.
MBS Available
Anticardiolipin Ab (IgG, IgM)
ELISA. MBS Item 71113. Widely available.
MBS Available
Anti-β2-Glycoprotein I Ab (IgG, IgM)
ELISA. MBS Item 71113. Standard in tertiary labs.
Essential
Full Blood Count (FBC)
Assess for thrombocytopenia, haemolysis.
Essential
Coagulation Screen (INR, APTT, Fibrinogen)
Baseline and to exclude other causes.
Referral Recommended
Renal Biopsy
For suspected APS nephropathy. Referral to Nephrology.

Management

Management is lifelong and tailored to clinical phenotype (thrombosis vs. obstetric), antibody profile, and underlying autoimmune disease (e.g., SLE).

Anticoagulation for Thrombotic APS

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Warfarin
Coumadin® · Marevan® · Vitamin K antagonist
Adult dose Dose-adjusted to target INR. Venous thrombosis: INR 2.0–3.0. Arterial thrombosis (esp. recurrent): consider INR 2.5–3.5. Lifelong therapy.
Paediatric dose Individualised, target INR as per adult. Complex; requires Haematology/Paediatric specialist.
Renal adjustment No dose adjustment. Monitor INR closely.
PBS status ✔ PBS General Benefit
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Do NOT use DOACs first-line. Clinical trials (e.g., TRAPS, ASTRAL-1) show rivaroxaban and apixaban are inferior to warfarin in APS, with significantly higher rates of recurrent thrombosis, especially in triple-positive patients. DOACs are generally contraindicated.

Antiplatelet & Immunomodulatory Therapy

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Aspirin (Low-Dose)
Cartia® · Astrix®
Adult dose 75–100 mg orally, once daily. For primary prophylaxis in asymptomatic aPL carriers, or combined with LMWH in obstetric APS.
PBS status ✔ PBS General Benefit
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Hydroxychloroquine
Plaquenil® · Quinoric® · DMARD
Adult dose 200–400 mg orally daily (≤5 mg/kg/day actual body weight). Anti-thrombotic and immunomodulatory. Strongly recommended in APS-SLE overlap.
Key Monitoring Baseline and annual ophthalmology review after 5 years (or sooner with risk factors).
PBS status ✔ PBS General Benefit for SLE/RA. May require Authority for isolated APS.

Obstetric APS Management

Treatment is with prophylactic anticoagulation to improve placental perfusion.

  • First-line: Low-dose aspirin (75–100 mg daily), commenced pre-conception or as soon as pregnancy is confirmed.
  • Add Prophylactic LMWH (e.g., Enoxaparin 40 mg SC daily) once foetal heart activity is confirmed, continued to 6 weeks post-partum.
  • Treatment-dose LMWH is used if there is a prior history of thrombosis.
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Post-partum: Continue anticoagulation (warfarin or LMWH) for at least 6 weeks post-partum, and lifelong if there is a history of thrombosis. Warfarin is safe in breastfeeding.

Catastrophic APS (CAPS) Management

A medical emergency requiring intensive care unit admission.

  1. Immediate anticoagulation: IV unfractionated heparin (UFH) bolus then infusion.
  2. High-dose corticosteroids: IV methylprednisolone 500–1000 mg daily for 3 days.
  3. Plasma exchange (PLEX) or Intravenous Immunoglobulin (IVIG): Especially if thrombotic microangiopathy is present.
  4. Treat precipitating trigger (e.g., infection, surgery).

Special Populations

🤰 Pregnancy
All Pregnant Patients with APS
Requires combined care with Obstetric Medicine and Haematology. Treatment as per obstetric protocol above. Avoid warfarin in first trimester (teratogenic).
👶 Paediatrics
Paediatric APS
Rare. Often associated with SLE. Diagnosis uses adult criteria. Anticoagulation management is complex; requires tertiary Paediatric Haematology.
💧 Renal Impairment
Warfarin & LMWH
No warfarin dose adjustment. LMWH (Enoxaparin) requires dose reduction in CrCl <30 mL/min (use UFH instead if severe). Monitor anti-Xa levels.
🛡️ SLE Overlap
Hydroxychloroquine
Considered mandatory in APS-SLE for disease control and thrombosis prevention.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

The burden of autoimmune disease and cardiovascular risk factors is higher in Aboriginal and Torres Strait Islander peoples, which may impact APS prevalence and outcomes. Consider APS in younger patients with unexplained thrombosis.

Access to Specialist Care
Diagnosis and long-term management require Haematology/Rheumatology, which may be remote. Utilise telehealth (MBS items 91822, 91823) and shared-care with local Aboriginal Medical Services (AMS).
Anticoagulation Monitoring
Regular INR monitoring for warfarin can be challenging in remote areas. Consider training for point-of-care INR testing at local clinics, or weekly dosing supervised by AMS if stable.
Medication Access & Cost
Ensure PBS co-payment concessions are accessed. Hydroxychloroquine and warfarin are PBS-listed but costs can accumulate. Engage AMS pharmacists for support.
Cultural Safety
Discuss lifelong therapy in a culturally safe context. Address concerns about injections (LMWH in pregnancy) and blood tests. Involve family and Aboriginal Health Workers.

📚 References

  1. 1. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
  2. 2. Cohen H, BJH, Efthymiou M, et al. British Society for Haematology Guidelines for the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012;157(1):47-58.
  3. 3. Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019;78(10):1296-1304.
  4. 4. Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome (TRAPS): a randomized trial. Blood. 2018;132(13):1365-1371.
  5. 5. Ordi-Ros J, Sáez-Comet L, Pérez-Conesa M, et al. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome: a randomized noninferiority trial. Ann Intern Med. 2019;171(10):685-694.
  6. 6. Cervera R, Serrano R, Pons-Estel GJ, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74(6):1011-1018.
  7. 7. Royal Australian College of General Practitioners (RACGP). Management of Venous Thromboembolism in Primary Care. East Melbourne: RACGP; 2021.
  8. 8. Australian Commission on Safety and Quality in Health Care (ACSQHC). Blood Management Standard. Sydney: ACSQHC; 2022.
  9. 9. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework. Canberra: AIHW; 2023.
  10. 10. Cervera R, Rodríguez-Pintó I, Espinosa G. The diagnosis and clinical management of the catastrophic antiphospholipid syndrome: A comprehensive review. J Autoimmun. 2018;92:1-11.