HemophiliaA/B and Factor Deficiencies

Question 1

Hemophilia A:

-Inheritance

Answer 1

X-linked recessive

-30% are sporadic

Question 2

Hemophilia A - Severity Classification:

-Severe (2)

Answer 2

• Spontaneous bleeding occurs

- F8 levels <1.0 U/dL (1%)

Question 3

Hemophilia A - Severity Classification:

-Moderate (2)

Answer 3

• Excessive bleeding w/ minor trauma

- F8 levels 1-5 U/dL

Question 4

Hemophilia A - Severity Classification:

-Mild

Answer 4

• Excessive bleeding following surgery or major trauma

- F8 levels >5 U/dL

Question 5

Hemophilia A - Laboratory Findings:

• Platelets
• PT
• TT
• aPTT

Answer 5

Hemophilia A - Laboratory Findings:

• Platelets - wnl
• PT - wnl
• TT - wnl
• aPTT - Prolonged

Question 6

T/F: In Hemophilia A the prolonged aPTT corrects completely in the 1:1 mixing study.

Answer 6

True

Question 7

Hemophilia A - Female Carriers:

• F8 Activity
• F8:vWF ratio
• aPTT
• Abnormal Bleeding

Answer 7

Hemophilia A - Female Carriers:

• F8 Activity - >50%
• F8:vWF ratio ~1:2 (normal 1:1)
• aPTT - wnl
• Abnormal Bleeding - None

Question 8

Hemophilia A - Factor VIII (8) gene.

-Size

Answer 8

Xq28

-Large, 26 exons

Question 9

What mutation is seen in 40-45% of severe hemophilia A in Caucasions?

Answer 9

Single Inversion mutation of intro22

Question 10

Antibodies to FVIII develop in what percentage of patients who receive FVIII replacement therapy?

Answer 10

33%

Question 11

What 2 patient groups (nonhemophiliacs) does antibodies to FVIII develop?
-Effect

Answer 11

Elderly Adults/Postpartum

-Severe bleeding

Question 12

What factor is deficient in Hemophilia B (Christmas disease)?
-Inheritance

Answer 12

Factor IX (9)
-X-linked recessive

Question 13

Hemophilia B - Laboratory Findings:

• Platelets
• PT
• TT
• aPTT

Answer 13

Hemophilia B - Laboratory Findings:

• Platelets - wnl
• PT - wnl
• TT - wnl
• aPTT - Prolonged

Question 14

Which Hemophilia (A or B) can be detected at Birth?

Answer 14

Hemophilia A
-F8 should be normal at birth

Hemophilia B
-F9 is normally low at birth

Question 15

What type of Hemophilia B is characterized by spontaneous remission following puberty?

Answer 15

Factor IX Leiden

Question 16

Isolated Inherited Factor Deficiencies (II,V,VII,X,XI).

-Inheritance

Answer 16

Autosomal Recessive

Question 17

Isolated Inherited Factor Deficiencies (II,V,VII,X,XI).

-Most common

Answer 17

Factor VII (7)

Question 18

Factor VII deficiency - Lab finding.

Answer 18

Isolated prolongation of PT

Question 19

Factor V (5) deficiency - Lab findings:

• PT
• PTT
• TT

Answer 19

Factor V (5) deficiency - Lab findings:

• PT - prolonged
• PTT - prolonged
• TT - wnl

Question 20

Factor X (10) deficiency - Lab findings:

• PT
• PTT
• DRVVT
• TT

Answer 20

Factor X (10) deficiency - Lab findings:

• PT - prolonged
• PTT - prolonged
• DRVVT - prolonged
• TT - wnl

Question 21

Factor XI (11) deficiency:

• What population
• Associated w/ syndrome

Answer 21

• Ashkenazi Jews (5-10% gene frequency)

- Noonan syndrome

Question 22

This factor deficiency is associated with delayed bleeding, umbilical stump bleeding, frequent miscarriages, delayed wound healing, and formation of hypertrophic scars?

Answer 22

Factor XIII (13) deficiency (Heterozygotes)

Question 23

Homozygous Factor XIII (13) deficiency:

-Complications (3)

Answer 23

• Severe bleeding diathesis
• Life-threatening umbilical stump bleeding
• Intracranial bleeds

Question 24

What is the most common combined factor deficiency?

Answer 24

Factor V and Factor VIII

F5/F8

Question 25

What gene is responsible for Combined Factor V and Factor VIII Deficiency?

Answer 25

LMAN1 (ERGIC-53)

Question 26

What are the quantitative fibrinogen abnormalities called?

Answer 26

Afibrinogenemia and Hypofibrinogenemia

Question 27

What is the qualititative fibrinogen abnormality called?

Answer 27

Dysfibrinogenemia

Question 28

Qualitative fibrinogen defects (Dysfibrinogenemia) cause what?

Answer 28

Bleeding or Thrombosis

Question 29

What is the most common 1st manifestation of inherited Afibrinogenemia and Hypofibrinogenemia (quantitative defects)?

Answer 29

Umbilical cord hemorrhage

Question 30

Congenital afibrinogenemia is associated with what lab values? -similar clinical manifestations as

Answer 30

Prolonged PT and aPTT (Immeasurable) | -Moderate/Severe Hemophilia A

Question 31

What acquired factor deficiency is sometimes found in patients with amyloidosis?

Answer 31

Factor X (10)

Question 32

Vitamin K is necessary for what?

Answer 32

y-carboxylation of factors 2,7,9,10,protein C/S

Question 33

Of the Vitamin K dependent coagulation factors, which has the shortest halflife? -2nd

Answer 33

``` Factor 7 (VII) -2-5 hrs ``` Protein C -6-8 hrs

Question 34

What is the most sensitive test for DIC? | -Specific?

Answer 34

Sensitive: -D-dimer Specific: -Fibrinogen