Antiphospholipid Antibody Syndrome 1 Definition s Disorder of

Antiphospholipid Antibody Syndrome 1

Definition s Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently raised levels of antiphospholipid antibodies. s Primary: Occurs alone s Secondary: Associated with other autoimmune or rheumatic diseases 2

Antiphospholipid Antibody A number of Abs directed against either phospholipids or plasma proteins that are bound to phospholipids. 3

APL Frequency Population Normal DVT PMR Behcet’s PSS ITP SS SLE Frequency (%) 1 -5 27% 20 -25 30 40 30 -50 4

Anti-Phospholipid antibodies s Lupus Anti-coagulant s Anti-cardiolipin antibody s Anti-ß 2 glycoprotein I antibody s False + serologic test for Syphillis 5

Lupus Anti-coagulant s A/B directed against plasma proteins bound to phospholipids s Blocks In Vitro assembly of prothrombinase s Prolongs s a. PTT s d. RVVT s KPC 6

Anti-cardiolipin antibody s React with phospholipids such as cardiolipin s Different immunoglobulin subclasses and isotypes are associated with anti-cardiolipin antibodies s Ig. G Ig. A Ig. M (Ig. G 1 -4) s Increased levels of Ig. G acl incurs a greater risk of thrombosis s 85% concordance LA and ACL 7

Anti-ß 2 glycoprotein I antibody s Inhibitor of coagulation (phospholipid binded) s Occurs alone in 11% s Found in large percentage of primary and secondary APS 8

False + serologic test for Syphillis s Phospholipid dependant tests s Syphillis antigen-cardiolipin 9

Location of Tests in Pathway 10 Levine, NEJM 2002

Pathogenesis of APS • Inflammation induce antibodies • Antibodies activate endothelial cells and platelets • Antibodies alter balance between thrombotic and fibrinolytic pathways 11

Pathogenesis-Other mechanisms s Activation of platelets s Enhanced monocyte expression of Tissue Factor s Inhibition of Prot C , Prot S and other coagulation factors s A/B against other proteins involved in coagulation s Heparin s Prothrombin s Platelet activating factor etc. s Complement activation 12

Disease associations s Long list of associated diseases s SLE s Main Groups s s Autoimmune Infections and drugs Neoplasms Genetic Other 13

Clinical Manifestations s Thrombotic s DVT s PE s Superficial thrombophlebitis s Obstetric morbidity s Early fetal loss 35. 4% s Late fetal loss 16. 9% s Dermatologic s Leg ulcers s Livedo reticularis s Musculoskeletal s Heme s Thrombocytopenia s Hemolytic anemia s Cardiac s Heart valve lesions s MI s Neuro s s Epilepsy Stroke TIAs Migraine s Renal s HTN s Arthralgias 14

Libman Sacks 15

Testing for APS s VDRL s LA (lupus anticoagulant) s a. PTT (activated partial thromboplastin time) s KCT (kaolin clotting time) s d. RVVT (dilute Russell viper venom test) s ACL (anti-cardiolipin) s ELISA s Anti-cofactor tests s s 2 -GP-I Prothrombin Annexin V Protein S Protein C 16

Sensitivity and Specificity for APS Harris. Lupus, 1998. 17

Criteria for Antiphospholipid Syndrome APS is present if at least 1 clinical and 1 lab criteria are met. s Clinical criteria s Vascular thrombosis s Pregnancy morbidity s Unexplained fetal death beyond 10 w s Premature birth before 34 w s 3 or more unexplained spontaneous Ab before 10 w s Lab criteria s a. CL-Ig. G or Ig. M in moderate or high titer 2 x over 6 weeks s LA on 2 occasions at least 6 weeks apart 18