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
| Name | Details |
|---|
| Primary APS | Antiphospholipid antibodies with thrombotic or related obstetric complications but no other underlying cause |
| Secondary APS | Antiphospholipid antibodies with thrombotic or related obstetric complications associated with a causative disease e.g. SLE |
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
| Clinical criteria (one or more) |
|---|
- [1]. Vascular thrombosis: One or more objectively confirmed episodes of arterial, venous or small vessel thrombosis occurring in any tissue or organ
- [2]. Pregnancy morbidity
- a) one or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation; or
- b) one or more premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia, pre-eclampsia or placental insufficiency; or
- c) Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation
- [3]. Laboratory criteria (one or more, present on 2 or more occasions at least 12 weeks apart using recommended procedures)
- 1. Lupus anticoagulant, detected according to the guidelines of the International Society on Thrombosis and Haemostasis
- 2. Anticardiolipin antibody of IgG and/or IgM isotype, present in medium or high titre (greater than 40 GPL or MPL, or greater than the 99th percentile), measured by a standardized ELISA
- 3. Anti-&beta 2-glycoprotein-1 antibody of IgG and/or IgM isotype, present in titre greater than the 99th percentile, measured by a standardized ELISA
|
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
| The Global Anti-Phospholipid Syndrome Score |
|---|
- Anticardiolipin antibodies (immunoglobulin G (IgG) or IgM isotype): 5 points
- Anti-ß2-glycoprotein antibodies (IgG or IgM isotype): 4 points
- Lupus anticoagulant: 4 points
- Anti-prothrombin/phosphatidylserine complex antibodies (IgG or IgM isotype): 3 points
- Hyperlipidaemia: 3 points
- Arterial hypertension: 1 point
|
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).