Antiphospholipid Antibody Syndrome(APS)

Sunil Kumar Daha

INTRODUCTIONConstellation of clinical conditions, associated with a

persistently positive test for an antiphospholipid antibody

Features:- - Recurrent venous and arterial thromboembolism - Adverse pregnancy outcomes (abortion >3 times) - Abnormal fetus after 10 weeks - Pre-eclampsia, eclampsia - Thrombocytopenia - Neurologic: Chorea, Migraine, Epilepsy -Renal and osteoarticular manifestations

Antiphospholipid antibodies (aPL) are directed against protein which binds to phospholipids

- Beta2-glycoprotein I - Protein C - Annexin V - Prothrombin

PathogenesisaPL binds to n-terminal domain of Beta2-

glycoprotein I

Glycoprotein binds to phospholipid on surface of endothelial cells, platelets,

monocytes and trophoblast

Alters function of those cells

Thrombosis / Miscarriage

Pathogenic clotting mechanisms mediated by aPL. aPL actions favor clot formation through several routes. (1)aPL interact with endothelial cells, primarily through binding of

β2GPI on the cell surface, and induce a procoagulant and proinflammatory endothelial phenotype.

(2) aPL upregulate tissue factor expression on endothelial cells and blood

monocytes, and promote endothelial leukocyte adhesion, cytokine secretion and PGE2 synthesis. (3) aPL recognize phospholipid-binding proteins expressed on platelets—aPL binding potentiates platelet aggregation induced by another agonist. (4) aPL interfere with plasma components of the coagulation cascade, by inhibiting anticoagulant activity, by affecting fibrinolysis, and by displacing the binding of the natural anticoagulant annexin A5 to anionic structures. These mechanisms all contribute to a procoagulant state that is necessary but not sufficient for clotting. Clot formation seems to require two steps: the presence of aPL provides the ‘first hit’, which produces clotting when accompanied by another procoagulant condition, a ‘second hit’. Complement activation seems to be necessary for clot formation in vivo. Abbreviations: aPL, anti-phospholipid autoantibodies; β2GPI, β2 glycoprotein I; PGE2, prostaglandin E2

Pathogenesis of antiphospholipid syndrome: Understanding the antibodies (PDF Download Available). Available from:

PRESENTATIONPrimarySecondary :SLE RA Systemic Sclerosis Sjogren’s syndromeCAPS (Catastrophic APS): rapidly progressing thromboembolic disease in 3 or more organs/ systems/ tissues

RISK GROUP- Women- SLE- White then black

INVESTIGATIONS

Anticardiolipin testLupus Anticoagulant testAnti Beta2- glycoprotein 1 test

For confirmation of APS, test result should be positive on at least 2 occasion >= 12 weeks apart.

TREATMENTWarfarin used for lifeLMW heparin + Warfarin aim to keep INR

between 2.0 – 3.0Warfarin + Aspirin (81 mg/ day)Aspirin reduces risk of thrombosis in aPL

positive individualsPregnancy: o Heparin + Aspirino IV immunoglobulin (IVlg) 400 mg/ kg

every day for 5 days may also prevent abortions

TREATMENT… Heparin-induced

thrombocytopenia and thrombosis syndrome: inhibitors of phospholipid-bound activated factor X (Fxa) fondaparinux 7.5 mg SC daily or rivaroxaban 10 mg PO daily

Effectiveness of clopidogrel and hydroxychloroquine have not been proven.

REFERENCEs

Kumar and Clark’s clinical medicine 8th edition

Davidson’s Principles & Practices of Medicine 21st edition

Harrison’s principal of internal medicine 19th edition

https://www.researchgate.net/publication/51111206_Pathogenesis_of_antiphospholipid_syndrome_Understanding_the_antibodies [accessed Apr 14, 2017].

Bonnie et al; Treatment of Antiphospholipid Syndrome; Up-To- Date

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