HemophiliaA/B and Factor Deficiencies Flashcards
Hemophilia A:
-Inheritance
X-linked recessive
-30% are sporadic
Hemophilia A - Severity Classification:
-Severe (2)
- Spontaneous bleeding occurs
- F8 levels <1.0 U/dL (1%)
Hemophilia A - Severity Classification:
-Moderate (2)
- Excessive bleeding w/ minor trauma
- F8 levels 1-5 U/dL
Hemophilia A - Severity Classification:
-Mild
- Excessive bleeding following surgery or major trauma
- F8 levels >5 U/dL
Hemophilia A - Laboratory Findings:
- Platelets
- PT
- TT
- aPTT
Hemophilia A - Laboratory Findings:
- Platelets - wnl
- PT - wnl
- TT - wnl
- aPTT - Prolonged
T/F: In Hemophilia A the prolonged aPTT corrects completely in the 1:1 mixing study.
True
Hemophilia A - Female Carriers:
- F8 Activity
- F8:vWF ratio
- aPTT
- Abnormal Bleeding
Hemophilia A - Female Carriers:
- F8 Activity - >50%
- F8:vWF ratio ~1:2 (normal 1:1)
- aPTT - wnl
- Abnormal Bleeding - None
Hemophilia A - Factor VIII (8) gene.
-Size
Xq28
-Large, 26 exons
What mutation is seen in 40-45% of severe hemophilia A in Caucasions?
Single Inversion mutation of intro22
Antibodies to FVIII develop in what percentage of patients who receive FVIII replacement therapy?
33%
What 2 patient groups (nonhemophiliacs) does antibodies to FVIII develop?
-Effect
Elderly Adults/Postpartum
-Severe bleeding
What factor is deficient in Hemophilia B (Christmas disease)?
-Inheritance
Factor IX (9) -X-linked recessive
Hemophilia B - Laboratory Findings:
- Platelets
- PT
- TT
- aPTT
Hemophilia B - Laboratory Findings:
- Platelets - wnl
- PT - wnl
- TT - wnl
- aPTT - Prolonged
Which Hemophilia (A or B) can be detected at Birth?
Hemophilia A
-F8 should be normal at birth
Hemophilia B
-F9 is normally low at birth
What type of Hemophilia B is characterized by spontaneous remission following puberty?
Factor IX Leiden
Isolated Inherited Factor Deficiencies (II,V,VII,X,XI).
-Inheritance
Autosomal Recessive
Isolated Inherited Factor Deficiencies (II,V,VII,X,XI).
-Most common
Factor VII (7)
Factor VII deficiency - Lab finding.
Isolated prolongation of PT
Factor V (5) deficiency - Lab findings:
- PT
- PTT
- TT
Factor V (5) deficiency - Lab findings:
- PT - prolonged
- PTT - prolonged
- TT - wnl
Factor X (10) deficiency - Lab findings:
- PT
- PTT
- DRVVT
- TT
Factor X (10) deficiency - Lab findings:
- PT - prolonged
- PTT - prolonged
- DRVVT - prolonged
- TT - wnl
Factor XI (11) deficiency:
- What population
- Associated w/ syndrome
- Ashkenazi Jews (5-10% gene frequency)
- Noonan syndrome
This factor deficiency is associated with delayed bleeding, umbilical stump bleeding, frequent miscarriages, delayed wound healing, and formation of hypertrophic scars?
Factor XIII (13) deficiency (Heterozygotes)
Homozygous Factor XIII (13) deficiency:
-Complications (3)
- Severe bleeding diathesis
- Life-threatening umbilical stump bleeding
- Intracranial bleeds
What is the most common combined factor deficiency?
Factor V and Factor VIII
F5/F8
What gene is responsible for Combined Factor V and Factor VIII Deficiency?
LMAN1 (ERGIC-53)
What are the quantitative fibrinogen abnormalities called?
Afibrinogenemia and Hypofibrinogenemia
What is the qualititative fibrinogen abnormality called?
Dysfibrinogenemia
Qualitative fibrinogen defects (Dysfibrinogenemia) cause what?
Bleeding or Thrombosis
What is the most common 1st manifestation of inherited Afibrinogenemia and Hypofibrinogenemia (quantitative defects)?
Umbilical cord hemorrhage
Congenital afibrinogenemia is associated with what lab values?
-similar clinical manifestations as
Prolonged PT and aPTT (Immeasurable)
-Moderate/Severe Hemophilia A
What acquired factor deficiency is sometimes found in patients with amyloidosis?
Factor X (10)
Vitamin K is necessary for what?
y-carboxylation of factors 2,7,9,10,protein C/S
Of the Vitamin K dependent coagulation factors, which has the shortest halflife?
-2nd
Factor 7 (VII) -2-5 hrs
Protein C
-6-8 hrs
What is the most sensitive test for DIC?
-Specific?
Sensitive:
-D-dimer
Specific:
-Fibrinogen
