hemophilia

Question 1

clinical features

Answer 1

• hemarthrosis
  *muscle bleeding

Question 2

coags in hemophilia A and B

Answer 2

prolonged PTT w/ correction in mixing study

Question 3

severe hemophilia criteria

Answer 3

<1% factor activity

Question 4

moderate hemophilia criteria

Answer 4

1-5% baseline factor activity

Question 5

mild hemophilia criteria

Answer 5

5-50% baseline factor activity

Question 6

Factor dosing in hemophilia A

Answer 6

1 unit/kg, which will raise factor VIII level by 2%
(1 to 2)
50 units/kg raises factor level to 100%
*Factor VIII has a binding partner (VWF) to enable it to remain in blood for longer than Factor IX

Question 7

Maintenance factor dosing in hemophilia A

Answer 7

25 u/kg at 12h often given as maintenance dose

Question 8

emicuzumab mechanism

Answer 8

binds to both the activated coagulation factor IX and to factor X, mediating the activation of the latter. This is normally the function of coagulation factor VIII, which is missing in haemophilia A patients (so it’s a factor VIII mimetic)

Question 9

Breakthrough drug for hemophilia A

Answer 9

emicizumab

Question 10

Factor dosing in hemophilia B

Answer 10

1 unit/kg, which will raise factor VIII level by 1%
(1 to 1)

Question 11

Goal factor levels perioperatively for minor surgeries

Answer 11

Above 50% for 3-5 days

Question 12

Goal factor levels perioperatively for major surgeries

Answer 12

Above 80% for 10-14 days

Question 13

Other drug that can be used in mild hemophilia A for mild bleeds

Answer 13

DDAVP

Question 14

Management of life threatening bleed in patient with possible but unknown inhibitor

Answer 14

bypass with recombinant factor seven

Question 15

How to test for an inhibitor

Answer 15

bethesda assay

Question 16

Bethesda assay interpretation

Answer 16

IF >5 bethesda units, you can’t treat with factor replacement (1 bethesda unit = 50% decline in factor 8 or 9).
*Give bypassing agent

Question 17

Drug contraindicated with novoseven

Answer 17

emicizumab (VTE)

Question 18

acquired hemophilia A management

Answer 18

• immunosuppression with steroids
• treat underlying cause

Question 19

Hemophilia A genetics most commonly

Answer 19

Most commonly due to Intron 22 or intron 1 inversion

Question 20

Hemophilia B genetics most commonly

Answer 20

Missense mutation

Question 21

Can female carriers ahve a bleeding phenotype?

Answer 21

Yes substantial variability in baseline factor levels among female carriers

Question 22

How can women be affected with heomphilia?

Answer 22

• skewed X inactivation
• de novo new mutation in woman who is a carrier
• 2 new de novo mutations
• compound heterozygote
• turner syndrome (missing x chromosome)
• vWD 2N (low levels of factor VIII)

Question 23

Goal nadir factor levels for CNS trauma/hemorrhage or major surgery

Answer 23

Greater than 80%

Question 24

Goal nadir factor levels for joint, muscle, GI tract, epistaxis, hematuria

Answer 24

30-50%

Question 25

How frequently hemophilia A pts need prophylaxis with new long acting product

Answer 25

Once weekly

Question 26

Primary ancillary treatments for hemophilia

Answer 26

• DDAVP
• fibrinolytics

Question 27

Hemophilia subtype more with higher incidence of inhibitors

Answer 27

Hemophilia A

Question 28

RF’s for inhibitor development - 1) genetic 2) ethnic 3) recombinant vs. plasma derived factor VIII

Answer 28

• larger gene deletions and nonsense mutations
• African American, hispanic
• Recombinant Factor 8

Question 29

What is a high titer bethesda unit

Answer 29

Greater than 5

Question 30

Options for preventing bleeding in hemophilia patients with inhbitors

Answer 30

• immune tolerance induction (expose pt to factor daily and they develop tolerance)
• re balancing therapies
• prevent bleeding with emicizumab

Question 31

Treatment of bleeding in hemophilia patients with inhibitors

Answer 31

1) rFVIIa
2) bypassing agents (eg FEIBA)
3) rPorcine Factor VIII if no cross-reactivity
4) r(human) factor VIII if B.U. titer low
*emicizumab is only used for prophylaxis

Question 32

Breakthrough drug for pts with inhibitors

Answer 32

emicizumab

Question 33

Contraindication to emicizumab use

Answer 33

FEIBA (VTE + TMA)

Question 34

Re-balancing therapy drugs for hemophilia

Answer 34

• fitusiran
• concizumab
• reduction in protein C and S levels

Question 35

Fitusiran mechanism

Answer 35

small RNA targeting antithrombin

Question 36

concizumab mechanism

Answer 36

Antibody to tissue factor inhibitor

Question 37

Obstacles to gene therapy for hemophilia

Answer 37

• neutralizing antibodies
• FVIII misfolding
• hepatotoxicity

Question 38

Treatment of hepatotoxicity from gene therapy

Answer 38

steroids

Question 39

Drug often used for oral surgery in hemophilia patients

Answer 39

Tranexamic acid

Question 40

How can a boy inherit hemophilia?

Answer 40

Mother has to be a carrier (boy receives Y chromosome from father)