Hemophilia A and B Lecture Notes

Hemophilia Overview

Hemophilia A

• Definition: Hereditary disorder of secondary hemostasis due to factor 8 deficiency.
• Genetics: X-linked recessive condition, predominantly affects males (1 in 5,000 males).
• Severity: Ranges from mild, moderate, to severe.
• Symptoms:
  • Delayed bleeding after cuts or surgery.
  • Deep bleeds presenting as spontaneous hemarthrosis (blood in joint spaces).
• Laboratory Findings:
  • Decreased factor 8 expression.
  • Increased PTT (Partial Thromboplastin Time).
  • Normal PT (Prothrombin Time) and INR (International Normalized Ratio).
• Treatment:
  • Mild: Desmopressin (DDAVP).
  • Severe: Factor 8 concentrate and tranexamic acid prophylactically.

Hemophilia B

• Definition: Hereditary disorder of secondary hemostasis due to factor 9 deficiency.
• Genetics: X-linked recessive condition, predominantly affects males (1 in 30,000 males).
• Symptoms:
  • Delayed bleeding after cuts or surgery.
  • Deep bleeds presenting as spontaneous hemarthrosis (blood in joint spaces).
• Laboratory Findings:
  • Decreased factor 9 activity.
  • Increased PTT.
  • Normal PT and INR.
• Treatment:
  • Factor 9 concentrate and tranexamic acid.

Coagulation Cascade Overview

• Activation:

  • Factor 7 (7a) and tissue factor activate factor 10 (10a).
  • Activated factor 10 cleaves small amounts of prothrombin to thrombin.
  • Thrombin activates factors 13, 11, 8, and 5.
  • Activated factor 11 cleaves factor 9 to 9a.
  • Thrombin activates factor 8, combining factor 8a and 9a to activate more factor 10.
  • Activated factor 10 (with 5a) cleaves large amounts of prothrombin to thrombin.
  • Thrombin converts fibrinogen to fibrin; factor 13 stabilizes fibrin into insoluble form.

• Key Focus: Factor 8 and 9 deficiencies result in inadequate fibrin clot formation due to insufficient thrombin activation.

Similarities and Differences Between Hemophilia A and B

Similarities

• Both are hereditary and x-linked recessive (male predominant).
• Both have increased PTT and involve secondary hemostasis disorders.
• Common presentations: delayed bleeding, deep bleeds, spontaneous hemarthrosis.

Differences

• Hemophilia A:
  • Caused by factor 8 deficiency.
  • More common (1 in 5,000 males).
  • Treatment includes desmopressin for mild cases, factor 8 concentrates, and tranexamic acid.
• Hemophilia B:
  • Caused by factor 9 deficiency.
  • Rarer (1 in 30,000 males).
  • Treatment involves factor 9 concentrates and tranexamic acid.

Conclusion

• Hemophilia A and B have similar clinical presentations and genetic patterns but differ in specific factor deficiencies and frequency.
• Treatments are tailored to the severity and specific factor deficiencies of each type.

Additional Resources

• For more details, refer to the coagulation cascade lesson and other hematology lectures.