Hemophilia

Basics

Caused by deficiency of functional factor VIII or factor IX
Lack of functional factor causes partial inactivation of coagulation cascade and impaired hemostasis
2 types:
- Hemophilia A: Factor VIII deficiency
- Hemophilia B (Christmas disease): Factor IX deficiency
Symptoms dependent on factor activity:
- 5–30% factor activity (mild hemophilia):
  - Bleeding with major trauma or surgery
- 1–5% factor activity (moderate hemophilia):
  - Bleeding secondary to trauma/surgery
  - Occasional spontaneous hemarthroses (<1 time per month)
- <1% factor activity (severe):
  - Spontaneous bleeding from infancy
  - May bleed as often as 1–2 times per week, often requiring factor replacement
Complications:
- Death from hemorrhage
- Recurrent joint bleeding leads to joint destruction and loss of function
- Transfusion-transmitted infections (risk reduced with purification of concentrates)
- Development of inhibitors (IgG antibodies to factors), which prevent hemostasis

Genetics

X-linked recessive, though 1/3 have a spontaneous mutation
Rare disease:
- Hemophilia A: 1 in 5–7,000 males
- Hemophilia B: 1 in 30,000 males
Prevalence of inhibitors: 20% of severe hemophilia A and <5% of severe hemophilia B

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