HEMOPHILIA

Question 1

Congenital single-factor deficiencies marked
by anatomic soft tissue bleeding.

Answer 1

Hemophilias

Question 2

Second to VWD in prevalence among congenital bleeding disorders

Answer 2

Hemophilias

Question 3

Hemophilias prevalence:

Answer 3

1:8000; mostly males

Question 4

Distribution (percentage) of hemophilia (VIII, IX, and other factors)

Answer 4

85%, 14%, 1%

Question 5

Other name for FACTOR VIII DEFIENCY

Answer 5

Classic Hemophilia or Hemophilia A

Question 6

Factor VII STRUCTURE

Answer 6

Two chain, 285,000 Dalton protein translated from the X CHROMOSOME

Question 7

VIIIa/IXa complex (other name)

Answer 7

Tenase complex (activates coagulation factor X at a rate 10,000 times faster than free factor IXa can cleave
factor X)

Question 8

Factor VIII Deficiency effect to thrombin production

Answer 8

Slows the coagulation pathway’s production of thrombin and leads to hemorrhage.

Question 9

Labile factors

Answer 9

Factor V and VIII

Question 10

Preservative used in the blood collected

Answer 10

citrate-dextrose-phosphate (provides 30-50 units/dl F8 activity after 28 days storage)

Question 11

Gene for FVIII

Answer 11

186 kilobases of the X chromosome

Question 12

Male hemizygotes, whose sole X chromosome contains a FVIII gene mutation

Answer 12

experience anatomic bleeding (female carriers do not)

Question 13

Chances of hemophilia a if (Female carrier + Unaffected man)

Answer 13

25% chance of a normal daughter
25%
chance of a carrier daughter
25% chance of a normal son
25% chance of a hemophilic son

Question 14

Hemophilia A inheritance if (Hemophiliac man + non-carrrier woman)

Answer 14

All sons= Normal
All daughters= Obligate carriers

Question 15

30% of newly diagnosis of hemophilia arise as a result of

Answer 15

Spontaneous Germline Mutation

Question 16

May mimic hemophilia A in males and females

Answer 16

VWD of the Normandy (2N) subtype

Question 17

Clinical manifestations of Hemophilia A

Answer 17

Anatomic bleeds with deep muscle and joint hemorrhage
Hematomas
Wound oozing
Bleeding (CNS and organs)

Question 18

Abnormal bleeding in neonatal period appear as

Answer 18

easy bruising, bleeding from the umbilical stump, postcircumcision bleeding, hematuria, or intracranial bleeding

Question 19

Severe hemophilia time of diagnosis

Answer 19

First year of life

Question 20

PT, PTT, and (1972) IX, X, VII, II results of an infant

Answer 20

Low (FVIII levels are similar to adults)

Question 21

Relationship of severity of Hemophilia A to FVIII activity

Answer 21

Inversely proportional

Question 22

FVIII activity less than 1 unit/dl

Answer 22

Severe (spontaneous or exaggerated bleeding in the neonatal period)

Question 23

Activity levels 1-5 units/dl

Answer 23

Moderate Hemophilia (early childhood)

Question 24

FVIII activity 5-40 units/dl

Answer 24

Mild Hemophilia (significant trauma)

Question 25

FVIII deficiency, FIX and FXI deficiency lab diagnosisi

Answer 25

PT- normal PTT- prolonged Fibrinogen- normal TT- normal <40 units/dl activity

Question 26

Deficiencies of contact factors (factor XII, high-molecular-weight kininogen, and prekallikrein)

Answer 26

Have no relationship to bleeding

Question 27

FVIII to VWF:Ag role in detecting FVIII deficiency

Answer 27

VWF production is unaffected by FVIII deficiency, good for differential diagnosis.

Question 28

Physiologic variables that affect FVIII activity and VWF:Ag assays

Answer 28

Estrogen levels Inflammation Physical stress Exercise

Question 29

If the FVIII to VWF:Ag ratio of the individual being tested is below the lower limit of the interval, she is likely to be

Answer 29

A carrier

Question 30

Therapy for mild to moderate hemophilia (to raise FVIII activity)

Answer 30

Desmopressin acetate (DDAVP) Stimate (Behring) w/ e-aminocaproic acid or tranexamic acid (anti fibrinolytic)

Question 31

Therapy for severe hemophilia

Answer 31

Coagulation Factor Concentrates

Question 32

Therapy for severe hemophilia

Answer 32

Coagulation Factor Concentrates

Question 33

Human plasma-derived FVIII (pdFVIII) concentrates examples

Answer 33

Alphanate (Grifols), Hemofil-M (Shire), Kogenate FS (Bayer), Humate-P (Behring), and Wilate (Octapharma).

Question 34

FVIII half life

Answer 34

8-12 hours (infusion twice-a-day)

Question 35

rFVIII products free of all human protein

Answer 35

Advate (Shire) -lower disease transmission

Question 36

How does the B-domain-deleted (BDDrFVIII) preparations are ReFacto render the molecule less immunogenic?

Answer 36

By deleting the large central B domains shortens the rFVIII molecules

Question 37

First extended half-life rFVIII which is a BDD-rFVIII fused with the Fc region of human immunoglobulin G1 (BDD-rFVIIIFc).

Answer 37

Eloctate

Question 38

Eloctate half-life

Answer 38

Nearly 20 hours (once every 4-5 days)

Question 39

Covalently conjugated with polyethylene glycol (PEG, “PEGylated” rFVIII). PEGylation is used in many drug applications; it extends the rFVIII half-life

Answer 39

Adynovate (Shire)

Question 40

Third extended half-life rFVIII formulation, “rFVIII-SingleChain,” that claims to closely resemble native FVIII.

Answer 40

Afstyla

Question 41

rFVIII- Single chain

Answer 41

Afstyla

Question 42

PEGylated

Answer 42

Adynovate

Question 43

Fc conjugated rFVIII

Answer 43

Eloctate

Question 44

Half-life of 12 to 15 hours which determines the ultimate plasma life span of FVIII. FVIII's dominant partner

Answer 44

VWF