1. Antiphospholipid Antibody Syndrome

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

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

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

5. Anti-Phospholipid antibodies
Lupus Anti-coagulant
Anti-cardiolipin antibody
Anti-ß2 glycoprotein I antibody
False + serologic test for Syphillis

6. Lupus Anti-coagulant
A/B directed against plasma proteins bound to phospholipids
Blocks In Vitro assembly of prothrombinase
Prolongs
aPTT
dRVVT
KPC

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

8. Anti-ß2 glycoprotein I antibody
Inhibitor of coagulation (phospholipid binded)
Occurs alone in 11%
Found in large percentage of primary and secondary APS

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

10. Location of Tests in Pathway
Levine, NEJM 2002

11. Pathogenesis of APS Inflammation induce antibodies
Antibodies activate endothelial cells and platelets
Antibodies alter balance between thrombotic and fibrinolytic pathways
50% APL cause drop in factor XII such that 80% of APS patients are low. Paradoxically low XII results in increaseed thrombosis

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

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

14. Clinical Manifestations
Thrombotic
DVT PE
Superficial thrombophlebitis
Obstetric morbidity
Early fetal loss 35.4%
Late fetal loss 16.9%
Dermatologic
Leg ulcers
Livedo reticularis
Musculoskeletal
Arthralgias
Heme
Thrombocytopenia
Hemolytic anemia
Cardiac
Heart valve lesions MI
Neuro
Epilepsy
Stroke
TIAs
Migraine
Renal
HTN

15. Libman Sacks

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

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

18. Criteria for Antiphospholipid Syndrome
APS is present if at least 1 clinical and 1 lab criteria are met.
Clinical criteria
Vascular thrombosis
Pregnancy morbidity
Unexplained fetal death beyond 10w
Premature birth before 34w
3 or more unexplained spontaneous Ab before 10w
Lab criteria
aCL-IgG or IgM in moderate or high titer 2x over 6 weeks
LA on 2 occasions at least 6 weeks apart
Definition: a syndrome marked by arterial and/or venous thrombosis, recurrent fetal loss and thrombocytopenia associated with autoantibodies with specificity for anionic phospholipids and their cofactors.