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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

Vascular thrombosis and complications of pregnancy are associated with autoantibodies directed toward phospholipids or phospholipid-binding proteins. APL is one of the thrombophilia disorders associated with potential arterial and venous thrombosis

About

• Also called Hughes syndrome and is a prothrombotic condition
• Antibodies to phospholipids or phospholipid-protein complexes
• Manifests as arterial and venous thrombosis, thrombocytopenia
• Recurrent fetal loss and may be primary or secondary
• Secondary causes: SLE, Connective tissue diseases, HIV, Hepatitis C, Lymphoproliferative disease
• Transient aPL positivity is often seen with acute infections and so diagnosis depends on repeated testing
• Antiphospholipid antibodies found in 1-5% in the general population increasing with age

Infographic

The Three Important Antiphospholipid antibodies

• Lupus anticoagulant (LA)
• Anticardiolipin antibodies (aCL)
• Anti- ß2-glycoprotein-1 (anti-ß2-GP1)

Aetiology

• An antibody binds to phospholipid on the platelet surface
• This inhibits the clotting cascade in vitro manifest by a prolonged APTT.
• In vivo it also binds to thrombomodulin on endothelium and slows Protein C activation causing a local prothrombotic state.
• Actually binds to Beta2-glycoprotein 1 which binds to phospholipid acting as a natural anticoagulant

Primary vs Secondary Classification

Clinical

• Female > Male ratio at least > 2:1
• Thrombocytopenia, migraine headaches, and livedo reticularis
• Recurrent fetal loss > 3 consecutive spontaneous miscarriages
• Arterial thrombosis
  • IHD/MI and TIA/Stroke
  • Catastrophic APS with multiple clots over a short time period
• Venous thrombosis
  • Cerebral venous sinus thrombosis
  • Budd Chiari syndrome
• Livedo reticularis most usually over the knees
• Heart / Vascular
  • Libman-sacks endocarditis
  • Myocardial infarction
  • Adrenal infarction
  • Renal artery stenosis
• Metatarsal fractures
• Guillain-Barré Syndrome

Revised classification criteria for the antiphospholipid antibody syndrome

The Global Anti-Phospholipid Syndrome Score [6]

• The Global Anti-Phospholipid Syndrome Score (GAPSS)210 is a scoring system to predict the risk of thrombosis (either first or recurrent) and pregnancy morbidity.
• The system consists of a combination of independent risk of thrombosis and pregnancy loss, including the antiphospholipid antibody profile and conventional cardiovascular risk factors.
• The GAPSS can be calculated for each patient by adding the points corresponding to the different risk factors

Investigations

• FBC: low platelets, Coomb's positive haemolysis
• ESR/CRP - normal
• Prolonged APTT
• ANA, dsDNA etc if SLE suspected
• Anticardiolipin [ACL] antibody - Serum ACL (IgG or IgM) or positive Lupus anticoagulant should be shown to be present on 2 or more occasions at least six weeks apart. The titre is essential.
• Lupus anticoagulant [LAC] causes a prolonged APTT that is not corrected by adding normal plasma. An abnormal Lupus Anticoagulant is the laboratory test result that confers the strongest risk for thrombosis.
• Transient false positives of low titre APL antibodies is seen especially in the elderly - it is wise to repeat several months apart, especially where there is clinical doubt
• Dilute Russell's viper's venom test is prolonged. False +ve test for syphilis
• Transoesophageal echocardiogram is strongly recommended in APS patients with ischaemic stroke as there is a high yield of valvular abnormalities.

Differentials

• Vasculitis
• SLE
• Thrombophilia
• Atrial myxoma

Management

• Long-term warfarin is given to patients who have had a thrombosis with INR commensurate with risk
• Aspirin 75 mg po od or Clopidogrel 75 mg po od may be an alternative if low risk or no thrombosis
• LMWH Heparin may be used in pregnancy
• Needs Expert help with Haematology
• Direct-acting oral anticoagulants (DOACs are not recommended

References

• [1]Miyakis S, Lockshin MD, Atsumi T, Branch DW, 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]Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies. Cochrane review
• [3]Antiphospholipid Antibodies and Stroke in Young Women
• [4]The risk of ischaemic stroke in primary antiphospholipid syndrome patients: a prospective study
• [5]Meroni, P. L. et al. Anti-beta 2 glycoprotein I antibodies in centenarians. Exp. Gerontol. 39, 1459-1465 (2004).
• [6]Sciascia, S., Bertolaccini, M. L., Roccatello, D. & Khamashta, M. A. Independent validation of the antiphospholipid score for the diagnosis of antiphospholipid syndrome. Ann. Rheum. Dis. 72, 142-143 (2013).