Hereditary coagulation disorders due to defects in clotting factors
What is primary hemostasis defect vs secondary hemostasis?
Primary is problems to do with platelets vs secondary is problem with activation of coagulation pathway
Coagulation disorder is associated with defects in the ______ pathway, with increased _____ time
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
Primary hemostasis consists of platelet _____, ____ and _______. While secondary hemostasis is fibrin_____
Primary: platelet activation/ aggregation and platelet plug formation
Secondary: fibrin stabilization
Hemophilia A is defect in factor ______. Hemophilia B is defect in factor _____. Hemophilia C is defect in factor _____.
(remember they are in alphabetical and numerical order)
Hemophilia A and B is most severe when diagnosed at this age: _______
Becomes less severe the later the diagnosis is
Hemophilia A and B: PT, PTT, vWF, and platelet counts?
What is a symptom of hemophilia A and B?
Inheritance pattern for Hemophilia A?
What is the mutation in Hemophilia A?
Deficiency of Factor VIII due to mutations in the F8 gene on the X chromosome
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
Which is the most common inherited coagulation disorder?
How is hemophilia A treated?
Infusion of recombinant F VIII or from donated plasma
What is the inheritance pattern for hemophilia B?
The Royal Disease refers to:
What is mutated?
Missense substitution of chromosome X in 75% of cases.
Hemophilia B is generally ____ severe than hemophilia A due to most mutations in B being ______, while most in A are _______
Hypomorphic – meaning some factor IX is produced
Null – meaning no factor VIII produced
T/F: like hemophilia A and B, hemophilia C is also X-linked Recessive
False; it is autosomal recessive
What is the mutation in hemophilia C?
deficiency in factor XI due to mutations in the F11 gene on chromosome 4
Hemophilia A has mutations on chromosome _____, hemophilia B has mutated chromosome ____ and hemophilia C has mutations on chromosome _____
Which of the hemophilia in which spontaneous bleeding is uncommon?
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?
Missense mutation Phe283Leu
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