Bleeding Disorders

Question 1

What are Weibel-Palade bodies?

Answer 1

They are located in the endothelium. They release vWF when stimulated.

Desmopressin stimulates release of vWF from the endothelial Weibel-Palade bodies.

Question 2

What is the mechanism of bleeding in Hemophilia?

Answer 2

Factor 8 and Factor 9 are responsible for the propagation phase which generates thrombin. In it’s absence, you end up with a bleeding phenotype.

Question 3

Describe the relationship between severity and underlying genetics in Hemophilia A.

Answer 3

Hemophilia A is X-linked recessive

• Intron 22 inversion is responsible for 40-50% of patients with severe hemophilia A.
• Mild to moderate generally have a point or missense mutation.

Question 4

What are the factor levels for severe, moderate and mild hemophilia?

Answer 4

• <1% - severe, present between birth and 3 years.
• 1-5% - moderate, present between 2-10 years.
• 5-40% - mild, present 5-21 years

Question 5

What is the differential diagnosis for intracranial bleeding?

Answer 5

• Hemophilia
• Factor XIII deficiency
• If there is a parenchymal bleed in the newborn, think fNAIT.

Question 6

Define the different types of prophylaxis in Hemophilia

Answer 6

1. Primary prophylaxis - either prior to any joint bleeding or before the second joint bleed
2. Secondary prophylaxis - after the second joint bleed
3. Tertiary prophylaxis - after onset of joint disease

Question 7

What is the expected factor response expected per 1 unit per kg of factor dosing?

Answer 7

Factor VIII - 1 unit/kg of factor will increase your factor VIII by 2%

Factor IX - 1 unit/kg of factor increases your factor IX by 1%

Question 8

What does APCC contain?

Answer 8

Plasma derived mixtures of factors II, VII, IX, and X (some activated).

Question 9

Describe normal factor levels in a neonate.

Answer 9

Neonates should have normal fibrinogen and normal to high factor VIII. *this means that low factor VIII in a newborn is VERY CONCERNING FOR HEMOPHILIA.

Factors V, VII, IX, X, XI, and XIII are all low in the liver.

Question 10

Which factors are made outside of the liver?

Answer 10

Factor V - liver AND megakaryocytes

Factor VIII - liver and endothelial cells

Factor XIII - liver and macrophages

vWF - endothelial cells and megakaryocytic

Question 11

What is the role of desmopressin in treating hemophilia?

Answer 11

It has a role in MILD HEMOPHILIA A.

Be careful in children under three years of age.