Antiphospholipid antibody syndrome
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Antiphospholipid antibody syndrome

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Antiphospholipid antibody syndrome Presentation Transcript

  • 1. ANTIPHOSPHOLIPID ANTIBODY SYNDROME Presenter : Demitrost Laloo
  • 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 Nomenclature of 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 blood donors 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 likely related 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
  • 8. Pathogenesis
  • 9. Pathogenesis Other possible contributory mechanisms  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 thrombosis and related consequences Deep vein thrombosis Livedo reticularis Pulmonary embolism Superficial thrombophlebitis Budd-Chiari syndrome Thrombosis in various other site
  • 11. Clinical features Arterial thrombosis and 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
  • 12. Clinical features Pregnancy morbidity Late Fetal losses >10 weeks Early fetal losses <10 weeks Early preeclampsia HELLP syndrome Premature birth
  • 13. Clinical features Osteoarticular manifestations Renal manifestations Arthralgia Severe hypertension Arthritis Renal failure Hematologic manifestations Neurologic of uncertain etiology Thrombocytopenia Migraine Epilepsy Chorea Cerebellar ataxia Transverse myelopathy Autoimmune hemolytic anemia
  • 14. Clinical features CAPS: Catastrophic Antiphospholipid 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
  • 15. Diagnostic criteria: Revised Sapporo classification
  • 16. Diagnostic criteria: Revised Sapporo classification
  • 17. Diagnostic criteria: Revised Sapporo classification  Definite APS : at least 1 clinical and 1 laboratory criteria  Classification avoided if <12 weeks and >5yrs separate +ve aPL test and clinical manifestation
  • 18. Other findings not included in the criteria but helpful in diagnosis
  • 19. CAPS criteria
  • 20. CAPS criteria
  • 21. Laboratory tests  Lupus   anticoagulant test 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
  • 22. Laboratory tests  Anti  ß2GP I 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
  • 23. Laboratory tests  False   does not 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
  • 24. Imaging  CT and MRI of 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
  • 25. 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
  • 26. Differential Dx           Hereditable deficiency of 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
  • 27. Treatment  Asymptomatic : no treatment  Venous/arterial 2.5) indefinitely  Recurrent thrombosis : warfarin (INR thrombosis : warfarin (INR 3-4) ± low dose aspirin
  • 28. 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
  • 29. Treatment  Valve    nodules or deformity Full anticoagulation if emboli or intracardiac thrombi demonstrated Valve replacement Thrombocytopenia   >50,000/cumm : no treatment <50,000/cumm : prednisone, IVIG
  • 30. Treatment CAPS :  Anticoagulation + corticosteroids + IVIG or plasmapheresis  Cyclophosphamide desperate situations and rituximab in
  • 31. 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
  • 32. No controlled studies in APS for  Clopidogrel  Pentoxyfylline  Argatobran  Hirudin  And other new anticoagulants
  • 33. Outcome  Long  term functional outcome 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
  • 34. Outcome  35% of obstretic APS 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
  • 35. THANK YOU