Coagulation Disorder Genetics

  1. What is hemophilia?
    Hereditary coagulation disorders due to defects in clotting factors
  2. What is primary hemostasis defect vs secondary hemostasis?
    Primary is problems to do with platelets vs secondary is problem with activation of coagulation pathway
  3. Coagulation disorder is associated with defects in the ______ pathway, with increased _____ time
    • Intrinsic
    • PTT
  4. T/F: to distinguish coagulation from platelet disorders, you look at increased PTT in coagulation.
    True; PTT is normally unchanged in platelets disorder except sometimes in von Willebrand disorder, but in most cases of hemophilia, PTT is increased and vWF are normal
  5. Primary hemostasis consists of platelet _____, ____ and _______. While secondary hemostasis is fibrin_____
    • Primary: platelet activation/ aggregation and platelet plug formation
    • Secondary: fibrin stabilization
  6. Hemophilia A is defect in factor ______. Hemophilia B is defect in factor _____. Hemophilia C is defect in factor _____.
    • VIII
    • IX
    • XI
    • (remember they are in alphabetical and numerical order)
  7. Hemophilia A and B is most severe when diagnosed at this age: _______
    • 1 month
    • Becomes less severe the later the diagnosis is
  8. Hemophilia A and B: PT, PTT, vWF, and platelet counts?
    • PT normal
    • PTT elevated
    • vWF normal
    • Platelets normal
  9. What is a symptom of hemophilia A and B?
    Spontaneous bleeding
  10. Inheritance pattern for Hemophilia A?
    X-linked Recessive
  11. What is the mutation in Hemophilia A?
    Deficiency of Factor VIII due to mutations in the F8 gene on the X chromosome
  12. What happens to the chromosome in Hemophilia A?
    • Chromosome X is inverted (45%), Between F8A in intro 22 and extragenic F8A
    • Other 55% is due to missense, nonsense, frameshift, insertion/deletion, and splicing mutations
  13. Which is the most common inherited coagulation disorder?
    Hemophilia A
  14. How is hemophilia A treated?
    Infusion of recombinant F VIII or from donated plasma
  15. What is the inheritance pattern for hemophilia B?
    X-linked recessive
  16. The Royal Disease refers to:
    Hemophilia B
  17. What is mutated?
    Missense substitution of chromosome X in 75% of cases.
  18. Hemophilia B is generally ____ severe than hemophilia A due to most mutations in B being ______, while most in A are _______
    • Less
    • Hypomorphic – meaning some factor IX is produced
    • Null – meaning no factor VIII produced
  19. T/F: like hemophilia A and B, hemophilia C is also X-linked Recessive
    False; it is autosomal recessive
  20. What is the mutation in hemophilia C?
    deficiency in factor XI due to mutations in the F11 gene on chromosome 4
  21. Hemophilia A has mutations on chromosome _____, hemophilia B has mutated chromosome ____ and hemophilia C has mutations on chromosome _____
    • X,
    • X,
    • 4
  22. Which of the hemophilia in which spontaneous bleeding is uncommon?
    Hemophilia C
  23. Hemophilia C occurs in which population? What is mutated between the two point mutations most commonly seen in this population: nonsense mutation vs missense mutation?
    • Ashkenazi Jews
    • Nonsense: Glu117X
    • Missense mutation Phe283Leu
  24. Glu117X is ____ mutation of hemophilia ____, which leads to homozygotes lack of Factor ____ proteins. Phe283Leu is ____ mutation of the same hemophilia type which causes a defect in ______, resulting in poor secretion of plasma factor activity
    • Nonsense
    • C
    • XI
    • Missense
    • Dimer formation
Card Set
Coagulation Disorder Genetics
HemeOnc Final