Antiphospholipid Syndrome (APLS) Part 1

1. Antiphospholipid Syndrome (APLS) Part 1 CPD Presentation HaroonAmini 22/09/2010

2. What is APS or Hughes Syndrome? • APS also known as “stickyblood” is a systemic autoimmune disease in which the body makes antibodies against its phospholipids. • APS characterized by thrombophylic state And obstetrical complications. • Primary APS is not associated with other diseases. • Secondary APS occurs in association with a disease i.e. SLE

3. APSAs cause blood clots in arteries and veins. Arterial thrombosis resulting in ischemia and necrosis of the foot

4. History • Early 1900, false positive test for syphilis. • 1950, the APS was first considered as a complication of the disease ‘lupus’. • 1950-1960, has something to do with clotting, pregnancy loss. • The APS was discovered in 1983 by Professor Graham Hughes and his team at St Thomas’s Hospital in London.

5. History • Professor Hughes realised APS could affect patients who were not suffering from Lupus. • International colleagues re-named the syndrome as ‘Hughes Syndrome’ to honour Professor Hughes. • 1990, discovery of B2-Glycoprotein 1

6. Frequency • The exact frequency of APS in the general population is unknown • 1-5% of the general population is believed to have APS. • It mostly affects females from puberty to 55 years old

7. 10-25% of women with recurrent miscarriage have APS. • 30% of strokes occurring in younger (under 55 years old) people are due to APS. • aPL antibodies are found in approximately 30-40% of patients with SLE, but only about 10% have APS

8. Pathophysiology • APS is a systemic autoimmune disease in which APLA reacts against protein that binds on anionic phospholipids on cell membrane, in particular cardiolipin and β2-glycoprotein I. • aCLA react with the vascular endothelial structure of blood vessels. This disturbs the balance of Prostoglandin E2- Thromboxane production.

9. Pathophysiology • aCLA binds ApoH, which in turn inhibits the function of Protein C over the Common Pathway of coagulation. • In APS some ABs bind to Protein S which is a co-factor for Protein C. • aCLA bind to platelet phospholipids, which increases the platelet aggregation. • In primary APS, the presence of 3 isotopes aCL and LAC is believed to be associated with consecutive miscarriages.

10. http://www.uspharmacist.com/content/c/10167/?t=women's_health,thrombosishttp://www.uspharmacist.com/content/c/10167/?t=women's_health,thrombosis

11. Etiology and research • The etiology of APS remains unknown. • The mechanism of excessive production of APLA and immune complex formation is not well understood. • But some studies have shown evidence of the development of clinical manifestation of APS i.e. Foetal loss, thrombocytopenia and neurological changes. • Deregulation of Complement system

12. Clinical symptoms • DVT in lower leg • Stroke • Recurrent miscarriage can occur prior to 20 weeks gestation • Placental infarction, early deliveries and still birth can occur in women with APS • Thrombocytopenia, dementia, headache

13. Diagnosis • Diagnosis requires clinical and laboratory findings with the clinical criteria being the primary method of diagnosis. • Laboratory finding includes; solid phase “ELISA assay” and Liquid phase coagulation assays “Lupus Anticoagulant”

14. Laboratory finding • Normal ACL result: IgG is below 23 ug/mL, while normal IgM and IgA is below 11 ug/mL.

15. Treatment • The disease can be treated by Aspirin and Warfarin as anticoagulant. • In pregnancy low molecular weight heparin and low dose of aspirin can be used.