Antiphospholipid syndrome

Last updated: August 21, 2023

Summarytoggle arrow icon

Antiphospholipid syndrome (APS) is an autoimmune disease associated with increased risk of thrombosis due to the presence of procoagulatory antibodies. APS can manifest in isolation or alongside other autoimmune diseases such as systemic lupus erythematosus (SLE). Typical clinical manifestations include recurring venous, arterial, and/or microcirculation thrombotic events (e.g., DVTs, stroke, TIAs) and obstetrical complications (e.g., recurrent miscarriages, premature births). APS should be suspected in patients with a history of thrombosis or miscarriage; diagnosis is confirmed by the detection of serum antiphospholipid antibodies (e.g., lupus anticoagulant, anticardiolipin antibodies). Management of acute thrombotic events varies widely depending on the clinical manifestation (e.g., stroke, DVT). Long-term management of APS (e.g., systemic anticoagulation with warfarin or heparin) is determined by the patient's risk of future thrombotic complications. Additional pharmacotherapy may be indicated for certain manifestations. Catastrophic antiphospholipid syndrome (CAPS) is a rare but severe form of APS that requires immediate treatment.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

APS usually manifests with recurring thrombotic events that may affect any organ. See also “Clinical features suggestive of underlying thrombophilia”.

Diagnosticstoggle arrow icon

Approach [2][4]

Thrombosis in APS is typically unprovoked (e.g., unprovoked DVT), recurrent, and/or manifests in unusual sites (e.g., kidneys, liver, retina). It is most commonly seen in younger individuals (< 50 years of age) and in individuals with comorbid autoimmune diseases (e.g., SLE).

Routine laboratory studies [2][4]

Obtain for all patients; results are nonspecific but may support the diagnosis.

Antiphospholipid antibodies (aPL antibodies) [1][4]

Reserve testing for patients with characteristic clinical features to avoid false positives.

Patients with APS can test false positive for syphilis (positive VDRL or RPR) because the antigen used in syphilis tests is cardiolipin.

Interpretation [2][4][5]

  • Symptomatic patients: The presence of ≥ 1 type of aPL antibody supports the diagnosis.
  • Asymptomatic patients
    • The presence of associated antibodies is not sufficient to establish a diagnosis.
    • Persistent positivity is associated with a higher risk of thrombotic and obstetric complications.

Positive lupus anticoagulant is associated with the highest risk of thrombosis.

A finding of positive aPL antibodies without clinical features is not sufficient to confirm a diagnosis of APS.

Additional studies [4]

Managementtoggle arrow icon

Management should be specialist-guided.

Approach [4][5]

Systemic anticoagulation is the cornerstone of treatment for thrombotic APS.

Thromboprophylaxis [4][5]

Primary thromboprophylaxis

Decisions on primary thromboprophylaxis should be made by a specialist based on individual thrombosis risk and bleeding risk.

Secondary thromboprophylaxis

Antiphospholipid antibodies can prolong the aPTT and consequently provide falsely elevated INR results, which may lead to inadequate anticoagulation. Consider measurement of factor X activity to confirm adequate anticoagulation. [4]

Thromboprophylaxis for APS during pregnancy [2][5]

Warfarin is teratogenic and therefore contraindicated during pregnancy.

Supportive care [5]

Management of catastrophic antiphospholipid syndrome [6][7]

CAPS is a rare but severe form of APS caused by acute and systemic small vessel thrombosis.

Diagnosis of CAPS is difficult because clinical presentation varies widely and approximately 50% of affected individuals have no history of aPL antibody positivity. [6]

The mortality rate of CAPS is approximately 50%, even with treatment. [6]

Referencestoggle arrow icon

  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): p.295-306.doi: 10.1111/j.1538-7836.2006.01753.x . | Open in Read by QxMD
  2. Schreiber K, Sciascia S, de Groot PG, et al. Antiphospholipid syndrome. Nat Rev Dis Primers. 2018; 4 (1).doi: 10.1038/nrdp.2017.103 . | Open in Read by QxMD
  3. Willis R, Pierangeli SS. Pathophysiology of the antiphospholipid antibody syndrome. Auto Immun Highlights. 2011; 2 (2): p.35-52.doi: 10.1007/s13317-011-0017-9 . | Open in Read by QxMD
  4. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018; 378 (21): p.2010-2021.doi: 10.1056/nejmra1705454 . | Open in Read by QxMD
  5. Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019; 78 (10): p.1296-1304.doi: 10.1136/annrheumdis-2019-215213 . | Open in Read by QxMD
  6. Asherson RA, Cervera R, de Groot PG, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003; 12 (7): p.530-534.doi: 10.1191/0961203303lu394oa . | Open in Read by QxMD
  7. Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: Updated diagnostic algorithms. Autoimmun Rev. 2010; 10 (2): p.74-79.doi: 10.1016/j.autrev.2010.08.005 . | Open in Read by QxMD

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