1. Hemophilia
2009

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
2009

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
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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
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5. 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 %
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6. Bleeding Episodes Common Hemorrhages Life Threatening Hemorrhages
soft tissue
muscle, joint
Life Threatening Hemorrhages
head / intracranial
neck abdominal / GI
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7. Complications of hemophilia
Joint destruction
chronic pain, joint arthritis / arthropathy, muscle atrophy
Inhibitor development
Exposure to plasma viruses
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8. JOINT BLEEDING IN HEMOPHILIA
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9. Treatment Methods Prophylaxis -- ⇩ bleeding episodes
Enhanced infusion protocol - ⇩ effects of bleeding
“On demand” therapy – treat each bleed episode
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10. Lyophilized Factor VIII produced by recombinant technology
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11. Radiographic Hemophilia Arthropathy
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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
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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
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14. Long-term outcome of recurrent hemarthroses: bony overgrowth, joint fusion, muscle atrophy
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15. Joint Outcome In Persons With Severe Factor VIII Deficiency Aledort LM et al: J Int Med 1994;236: (% of patients with each # of abnormal joints at ages 6-31 yrs)
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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
2009