Hemophilia

Question 1

what is hemophilia?

Answer 1

a bleeding disorder resulting from defects in factors of the coagulation cascade

the mutations lead to decreased activity of their respective clotting factors, an inability to activate factor X, and a defect in the formation of fibrin

due to the inability to form fibrin, excessive bleeding occurs in individuals afflicted with hemophilia, especially after trauma

Question 2

what are the two types of hemophilia?

Answer 2

hemophilia A

hemophilia B

both are rare but hemophilia A is more common

Question 3

what is hemophilia A?

Answer 3

a result of mutations in the factor VIII gene

in the intrinsic arm of the coagulation cascade, factor VIII serves as a cofactor for factor IX.

they cooperate to activate factor X, leading to the formation of fibrin

Question 4

what is hemophilia B?

Answer 4

a result of mutations in the factor IX gene

Question 5

describe the difference between hemophilia A and B

Answer 5

Hemophilia A is a result of a defect in factor VIII

hemophilia B is a result of a defect in factor IX

both of these factors work together to activate factor X in the intrinsic arm of the coagulation cascade

mutations lead to decreased activity of their respective clotting factors, an inability to activate factor X, and a defect in the formation of fibrin

Question 6

what’s the inheritance of hemophilia A and B?

Answer 6

both x-linked recessive

mostly seen in males

very uncommon in females

most hemophilia cases are inherited, but about 30% of hemophilia A cases arise from spontaneous mutations in the factor VIII gene

Question 7

when would a woman get hemophilia A?

Answer 7

hemophilia A can still be observed in heterozygous females in the rare event that the X chromosome carrying the normal factor VIII gene is inactivated in a high proportion of cells

Question 8

Why are men more likely to have hemophilia?

Answer 8

Hemophilia is an X-linked recessive disease. Men have only one X chromosome.

Question 9

what are the clinical features of hemophilia?

Answer 9

clinical presentation is a direct result of the inability to form fibrin

• easy bruising
• uncontrolled hemorrhage after trauma/procedures
• joint deformities

Question 10

what happens to the joints of people with hemophilia?

Answer 10

Parts of the body that are subject to repeated mechanical stresses, such as the joints, often experience ‘spontaneous’ hemorrhages (hemarthroses) that can ultimately result in joint deformities

Question 11

do people with hemophilia have petechiae?

Answer 11

no!

disorders that impair platelet plug formation, like von Willebrand disease, can be confused with hemophilia, but the presence of petechiae helps to differentiate them

Question 12

what is von willebrand disease?

Answer 12

disorder caused by caused by a defect in von Willebrand factor (vWF),

vWF anchors platelets to damaged blood vessels and protects circulating factor VIII from degradation

Question 13

how is von willebrand disease inherited?

Answer 13

autosomal dominant

Question 14

what are the effects of von willebrand factor?

Answer 14

increased bleeding tendency

Question 15

why do von willebrand disease and hemophilia A get confused sometimes?

Answer 15

Severe forms of vWF can strongly resemble the clinical features of hemophilia A due to an inability to stabilize circulating factor VIII

Question 16

how is the severity of hemophilia A classified?

Answer 16

1. severe: factor VIII activity levels 1% of normal
2. moderate: 2-5% of normal factor VIII activity
3. mild: 6-30% of normal factor VIII activity

Question 17

what tests are used to diagnose hemophilia?

Answer 17

1. PTT: measures intrinsic coagulation pathway

PT: tests extrinsic coagulation pathway

Question 18

what test results do you expect in hemophilia?

Answer 18

prolonged PTT because hemophilia causes defects in the intrinsic arm of the coagulation cascade

normal PT because extrinsic arm of coagulation cascade is unaffected

Question 19

what would a mixing test for hemophilia show?

Answer 19

PTT returns to normal and is no longer prolonged

when normal plasma is mixed with the patient’s blood, the missing clotting factors are restored to the blood

Question 20

how do you confirm hemophilia A?

Answer 20

a specific assay for factor VIII is used to confirm hemophilia A

Question 21

can you clinically distinguish hemophilia A and B?

Answer 21

eh not really

this is because factor IX cooperates with factor VIII in the activation of factor X, and deficiencies of both factor IX and factor VIII result in impairment of the intrinsic arm of the coagulation cascade

also, hemophilia b also has a prolonged PTT and normal PT

Question 22

how do you differentiate hemophilia A and B?

Answer 22

by using specific assays for factor IX

Question 23

how do you treat hemophilia?

Answer 23

both hemophilia A and B are treated by replacing the deficient clotting factor with recombinant protein infusions

Question 24

what’s a problem that you could run into with recombinant protein infusions used to treat hemophilia?

Answer 24

some patients with hemophilia A develop antibodies to recombinant factor VIII because their bodies recognize it as a foreign protein

in these patients PTT is not corrected when mixed with normal plasma because antibodies bind the free factor VIII, preventing its function

Question 25

what drug can be used to treat mild hemophilia A?

Answer 25

desmopressin

the drug can increase the release of von Willebrand factor (vWF)

vWF binds to and stabilizes factor VIII, levels of factor VIII may increase

this treatment is effective in types of hemophilia A where the gene mutation reduces production of functional factor VIII

Question 26

when is desmopressin not effective?

Answer 26

hemophilia A cases where the gene mutation results in loss of factor VIII function

desmopressin is used for when the gene mutation reduces production of functional factor VIII because desmopressin can increase the release of von Willebrand factor which stabilizes/protects factor VIII

Question 27

Why is PTT prolonged in hemophilia, but PT unaffected?

Answer 27

PTT is prolonged because it assesses the function of the intrinsic arm of the coagulation cascade, and hemophilia A and B affect factors important for the function of this part of the cascade.

PT is normal because it tests the function of the extrinsic arm of the coagulation cascade, which is unaffected in hemophilia.

Question 28

what is factor I deficiency?

Answer 28

fibrinogen deficiency

Question 29

what is factor II deficiency?

Answer 29

prothrombin deficiency

Question 30

what is factor V deficiency?

Answer 30

aka Owren’s disease, parahemophilia, labile factor deficiency, proaccelerin deficiency

Question 31

what is factor VII deficiency?

Answer 31

proconverwtin deficiency

Question 32

what is factor X deficiency?

Answer 32

Stuart-Prower factor deficiency

Question 33

what is factor XI deficiency?

Answer 33

aka Hemophilia C, plasma thromboplastin antecedent (PTA) deficiency, Rosenthal syndrome

Question 34

what is factor XII deficiency?

Answer 34

Hageman factor deficiency

Question 35

what is factor XIII deficiency?

Answer 35

Fibrin stabilizing factor deficiency

Question 36

A father, diagnosed with hemophilia B, is planning to have children with his wife, but is worried that his children will inherit his bleeding disorder. If the wife has no family history of bleeding disorders, and the couple has a son, what are the chances his son has the disease?

Answer 36

0%

its x-linked recessive

Question 37

A patient comes to you complaining of very easy bruising and bleeding that takes a very long time to stop. What would lead you to believe that your patient does not have hemophilia?

Answer 37

petechiae

petechiae are typically found in disorders that impair platelet plug formation, such
as von Willebrand disease.