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Antiphospholipid antibody syndrome
Antiphospholipid antibody syndrome (APS) is an autoimmune condition characterized by arterial or venous blood clots and/or pregnancy morbidity in the presence of antibodies that target phospholipid-binding plasma proteins. It can occur on its own (primary) or with other autoimmune diseases (secondary). APS is diagnosed based on clinical criteria of blood clots or pregnancy complications along with positive laboratory tests for antiphospholipid antibodies. Treatment involves blood thinners like warfarin to prevent clots. Prognosis can be poor as permanent organ damage or disability can occur in a third of patients within 10 years.
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Antiphospholipid antibody syndrome
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- 2. Introduction Antiphospholipid antibody syndrome(APS) is an autoimmunity-mediated acquired thrombophilia characterised by : It arterial or venous thrombosis and/or pregnancy morbidity in presence of autoantibodies against phospholipid(PL)- binding plasma proteins maybe Primary : occuring alone Secondary : in association with other autoimmune disease
- 3. Classification and Nomenclatureof Antiphospholipid Antibodies : Antibodies against cardiolipin (aCL) Antibodies against β2 Glycoproptein I (anti-β2GPI) Lupus anticoagulant(LA): heterogeneous group of antibodies directed also against PL binding proteins, mainly β2GPI and prothrombin Antibodies against phospholipids/cholesterol complexes detected as biologic false-positive serologic test for syphilis (BFP-STS) and Venereal Disease Research Laboratory Test (VDRL)
- 4. Epidemiology In normal blooddonors Low titer, transient aCL : 10% Moderate-high titer aCL or positive LA : <1% Prevalence females increases with age, more common in
- 5. Epidemiology Antiphospholipid antibodies (aPL)positivity in 10-40% SLE approx. 20% Rheumatoid arthritis 10% of 1st stroke patient, more in young(upto 29%) 20% in women with 3 or more consecutive fetal losses 14% in recurrent venous thromboembolic disease
- 6. Pathogenesis Trigger unknown Preceding aPL infection have been proposed binds to phospholipid-binding plasma protein ß₂ GP I
- 7. Pathogenesis aPL most likelyrelated to thrombosis through multiple mechanisms Activation of the classical complement pathway Expression of adhesion molecules and tissue factor Activation of monocytes and PMN: release of proinflammatory mediators and initiation of prothrombotic stage Activation of p38 MAPK and NFkB: intracellular signaling cascade
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- 9. Pathogenesis Other possible contributorymechanisms inhibition of coagulation cascade reactions catalyzed by phospholipids induction of tissue factor expression on monocytes reduction of fibrinolysis interaction with the annexin V anticoagulant shield in the placenta
- 10. Clinical features Venous thrombosisand related consequences Deep vein thrombosis Livedo reticularis Pulmonary embolism Superficial thrombophlebitis Budd-Chiari syndrome Thrombosis in various other site
- 12. Clinical features Arterial thrombosisand related consequences Stroke Cardiac valve thickening/dysfunction and/or Libman-Sacks vegetation's TIA Myocardial ischemia and coronary bypass thrombosis Leg ulcers and/or digital gangrene Arterial thrombosis in the extremities Retinal artery thrombosis/amaurosis fugax Ischemia of visceral organs or avascular necrosis of bone Multi-infarct dementia
- 13. Clinical features Pregnancy morbidity LateFetal losses >10 weeks Early fetal losses <10 weeks Early preeclampsia HELLP syndrome Premature birth
- 14. Clinical features Osteoarticular manifestations Renalmanifestations Arthralgia Severe hypertension Arthritis Renal failure Hematologic manifestations Neurologic of uncertain etiology Thrombocytopenia Migraine Epilepsy Chorea Cerebellar ataxia Transverse myelopathy Autoimmune hemolytic anemia
- 15. Clinical features CAPS: CatastrophicAntiphospholipid Syndrome Rare, abrupt, life threatening, mortality as high as 48% despite effective treatment Multiple thrombosis of medium and small arteries involving multiple organs over a period of days Causing: Stroke Cardiac, hepatic, adrenal, renal and intestinal infarction Peripheral gangrene
- 16. Diagnostic criteria: Revised Sapporoclassification
- 17. Diagnostic criteria: Revised Sapporoclassification
- 18. Diagnostic criteria: Revised Sapporoclassification Definite APS : at least 1 clinical and 1 laboratory criteria Classification avoided if <12 weeks and >5yrs separate +ve aPL test and clinical manifestation
- 19. Other findings notincluded in the criteria but helpful in diagnosis
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- 22. Laboratory tests Lupus anticoagulanttest More specific but less sensitive Requires a 4-step process Anticardiolipin Sensitive but not specific Standardized ELISA test for IgG and IgM Moderate to high titer required for diagnosis
- 23. Laboratory tests Anti ß2GPI Standardized ELISA for IgG and IgM Positive aPL test requires a repeat test after 12 or more weeks to rule out transient, clinically unimportant antibody
- 24. Laboratory tests False doesnot fulfill laboratory criteria Order aPL test ANA positive syphilis test and Anti-dsDNA Detected in aprrox. 45% primary APS Does not mandate additional diagnosis of SLE Other tests: Complete hemogram Urine examination
- 25. Imaging CT and MRIof brain for stroke CT angio or MR angiography if clinical findings suggest medium or large vessel disease Doppler study for DVT Echocardiography or cardiac MRI for vegetations or intracardiac thrombi
- 26. Pathology Biopsy of renal,skin or other tissues Thrombotic occlusion of all caliber arteries and veins Acute and chronic endothelial injury Recanalisation in late lesions
- 27. Differential Dx Hereditable deficiencyof Protein C, Protein S, antithrombin III Factor V Leiden and antithrombin mutations Hyperhomocysteinemia Thrombocytopenic purpura Septicemia Disseminated Intravascular Coagulation Hemolytic Uremic Syndrome Polyarteritis nodusa Myxoma Sneddon’s syndrome
- 28. Treatment Asymptomatic : notreatment Venous/arterial 2.5) indefinitely Recurrent thrombosis : warfarin (INR thrombosis : warfarin (INR 3-4) ± low dose aspirin
- 29. Treatment Pregnancy 1st pregnancy: no treatment Single pregnancy loss <10 weeks : no treatment >1 fetal loss or ≥3 (pre) embryonic loss, no thrombosis : prophylactic heparin + low dose aspirin throughout pregnancy, discontinue 6-12 weeks postpartum Thrombosis regardless of pregnancy history: therapeutic heparin or low dose aspirin throughout pregnancy, warfarin postpartum
- 30. Treatment Valve nodules ordeformity Full anticoagulation if emboli or intracardiac thrombi demonstrated Valve replacement Thrombocytopenia >50,000/cumm : no treatment <50,000/cumm : prednisone, IVIG
- 31. Treatment CAPS : Anticoagulation+ corticosteroids + IVIG or plasmapheresis Cyclophosphamide desperate situations and rituximab in
- 32. Treatment Aspirin LMW :81-325mg once daily heparin : Prophylactic dose : 30-40mg subcutaneously/day Therapeutic dose : 1 mg/kg, s/c BD or 1.5mg/kg OD
- 33. No controlled studiesin APS for Clopidogrel Pentoxyfylline Argatobran Hirudin And other new anticoagulants
- 34. Outcome Long term functionaloutcome is poor At 10yrs : 1/3rd developed permanent organ damage and 1/5th unable to perform everyday activities Pulmonary hypertension, neurological involvement, myocardial ischemia, gangrene of extremities and catastrophic APS associated with worse prognosis
- 35. Outcome 35% of obstreticAPS without thrombosis developed aPL-related clinical events during a 8yr follow up Long term outcome of children born to APS pregnancies unknown Many need valve replacement due to severe valvular disease Rarely may develop renal failure Serious perioperative complications may occur despite prophylaxis
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