1. Hemophilia 2008

2. What is Hemophilia? Hemophilia is an inherited bleeding disorder in which there is a deficiency or lack of factor VIII or factor IX clotting factor proteins 2008 www.hemoalliance.org

3. Hereditary Bleeding Disorders Hemophilia A - absence or deficiency of FVIII Hemophilia B - absence or deficiency of FIX Von Willebrand - vWF is missing or faulty 2008 www.hemoalliance.org

4. Incidence of Hemophilia One in 5,000-7,500 live male births Affects 20,000 in the U.S. 30% spontaneous mutation All races and socioeconomic groups are equally affected 2008 www.hemoalliance.org

5. Clinical Severity of Hemophilia ClinicalFraction ofCoagulationBleeding SeverityHemophilia FactorTendency Cases Activity ------------------------------------------------------------------------------------------ Severe60% 0-1%Spontaneous without trauma Moderate15% 1-5%With mild trauma Mild25% 5-25%With significant trauma or surgery Normal 50-150% 2008 www.hemoalliance.org

6. Bleeding Episodes Common Hemorrhages – soft tissue – muscle, joint Life Threatening Hemorrhages – head / intracranial – neck abdominal / GI 2008 www.hemoalliance.org

7. Complications of hemophilia Joint destruction chronic pain, joint arthritis / arthropathy, muscle atrophy Inhibitor development Exposure to plasma viruses 2008 www.hemoalliance.org

8. JOINT BLEEDING IN HEMOPHILIA 2008 www.hemoalliance.org

9. Treatment Methods Prophylaxis -- ⇩ bleeding episodes Enhanced infusion protocol - ⇩ effects of bleeding “On demand” therapy – treat each bleed episode 2008 www.hemoalliance.org

10. Lyophilized Factor VIII produced by recombinant technology 2008 www.hemoalliance.org

11. Radiographic Hemophilia Arthropathy 2008 www.hemoalliance.org

12. Inhibitor Circulating antibody to factor VIII or IX Affects 8-20% of severe fVIII patients Affects 1-3% of FIX Treatment – increase factor – bypass antibodies – immune intolerance 2008 www.hemoalliance.org

13. Therapies for Hemophilia patients with Inhibitors Adequate factor VIII to overwhelm the inhibitor and maintain an adequate factor VIII level Porcine factor VIII Designer human-porcine hybrid FVIII molecules rFVIIa (NovoSeven) FEIBA Plasmapheresis 2008 www.hemoalliance.org

14. Long-term outcome of recurrent hemarthroses: bony overgrowth, joint fusion, muscle atrophy 2008 www.hemoalliance.org

15. Joint Outcome In Persons With Severe Factor VIII Deficiency Aledort LM et al: J Int Med 1994;236:391-9. (% of patients with each # of abnormal joints at ages 6-31 yrs) 2008 www.hemoalliance.org

16. Prevention of Joint Disease in Hemophilia Early treatment of joint hemorrhages Arrest of synovitis: surgical removal, radiosynoviorthesis Use of higher doses, multiple infusions Prevention of bleeding with routine replacement of factor VIII on a regular schedule 2008 www.hemoalliance.org