Hemophilia 2009

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 2009 www.hemoalliance.org

Hereditary Bleeding Disorders Hemophilia A - absence or deficiency of FVIII Hemophilia B - absence or deficiency of FIX Von Willebrand - vWF is missing or faulty 2009 www.hemoalliance.org

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 2009 www.hemoalliance.org

Clinical Severity of Hemophilia Clinical Fraction of Coagulation Bleeding Severity Hemophilia Factor Tendency Cases Activity ------------------------------------------------------------------------------------------ Severe 60% 0-1% Spontaneous without trauma Moderate 15% 1-5% With mild trauma Mild 25% 5-25% With significant trauma or surgery Normal 50-150% 2009 www.hemoalliance.org

Bleeding Episodes Common Hemorrhages Life Threatening Hemorrhages soft tissue muscle, joint Life Threatening Hemorrhages head / intracranial neck abdominal / GI 2009 www.hemoalliance.org

Complications of hemophilia Joint destruction chronic pain, joint arthritis / arthropathy, muscle atrophy Inhibitor development Exposure to plasma viruses 2009 www.hemoalliance.org

JOINT BLEEDING IN HEMOPHILIA 2009 www.hemoalliance.org

Treatment Methods Prophylaxis -- ⇩ bleeding episodes Enhanced infusion protocol - ⇩ effects of bleeding “On demand” therapy – treat each bleed episode 2009 www.hemoalliance.org

Lyophilized Factor VIII produced by recombinant technology 2009 www.hemoalliance.org

Radiographic Hemophilia Arthropathy 2009 www.hemoalliance.org

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 2009 www.hemoalliance.org

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 2009 www.hemoalliance.org

Long-term outcome of recurrent hemarthroses: bony overgrowth, joint fusion, muscle atrophy 2009 www.hemoalliance.org

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) 2009 www.hemoalliance.org

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 2009 www.hemoalliance.org