Transcript دکتر هورفر-کمبود فاکتور 7-هموفیلی

Factor VII Deficiency
Diagnosis and Management
Hamid Hoorfar MD
Inherited Blood Disorders Clinic
Esfahan Medical Sciences University
2014
• Factor VII is a vit K dependent clotting factor belonging to the
extrinsic pathway.( serocovertin , stable factor)
• FVII is a protein with 406 AA single chain ( 50 kDa).
• In the bloodtream FVIIa is the active portion of the FVII mass
and is detectable in normal concentration as low as 5-10 ng.(12% of zymogen)
• The factor VII gen is located on chromosome 13 upstream of
factor X and contains 9 exons.
Congenital factor VII Deficiency
Clinical manifestations
 Heterozygotes are usually asymptomatic while homozygotes and
compound heterozygotes are develop hemorrhagic tendency.
 Age and type of first bleeding are variables and correlate with
clinical severity.
 Bleeding symptoms ranging from severe to mild or even asymptomatic
forms as the activity of Factor VII does not correlate well with bleeding
tendency.
 IRF7 research group proposed the classification of bleeding phenotype
as hemophilia like , platelet like & asymptomatic.
 ICH, GI and joint bleeds classified as severe bleedings associated with
FVII levels < 5IU/dl ,without a clear relationship to the type of gene
defect.
 Menorrhagia is a very frequent type of bleeding in women with F7
deficiency (63%)
Clinical manifestations
IRF7 database (228 patients)
Symptomes
No.
%
Epistaxis
190
83
Easy bruising
Gum bleeding
Muscle hematoma
Hemarthrosis
Gastrointestinal
Hematuria
CNS bleeding
Postoperative bleeding
143
95
57
58
44
26
17
78
62
42
21
22
14
12
7
34
Clinical manifestations
IRF7 database (174 female)
Symptomes
No.
%
Epistaxis
98
56
Easy bruising
Gum bleeding
Muscle hematoma
Hemarthrosis
GI bleedings
Hematuria
CNS bleedings
Thrombosis
Postoperative bleedings
Menorrhagia
83
59
28
28
24
9
8
5
40
100
48
34
16
16
14
5
5
3
30
63
Diagnosis of Factor VII deficiency
A. Prolonged PT from moderate to markedly prolonged and
normal PTT
A. FVIIc is the confirmatory test for diagnosis
A.
Factor VII deficiency has been found to be associated with
hepatic congenital enzymic defects ( dubin – johnson and
gilbert syndromes)
A.
Only 51.4% of subjects with Factor VII deficiency were
diagnosed within 6 months after the first symptoms.
Treatment of bleeding in FVII deficiency
 Prevention and treatment of bleeding resides in the
replacement of the missing factor.

Because of short biological half life of FVII repeated
administration every 6-8 hours is needed.
 FFP, Prothrombin complex(PCC), plasma derived FVII
concentrate and recombinant FVIIa available options.
 Factor VIIa is today considered the first line product for
replacement therapy in FVII deficiency .
Treatment materials for congenital FVII deficiency
Materials
Potency
Dosage
Advantages
Disadvantages
FFP
1
10 ml/Kg
Low cost
Easy avaiable
Limited
effectiveness,risk
of overload,risk
of
virus
transmission
PCC
5-10
25-35 iu/kg
Suitable for
surgery,virally
attenuated
Risk
of
thrombosis,Other
vit K dependent
factors
have
higher
concentrates
pd FVII
concentrate
20-30
10-30 IU/kg
Suitable for
surgery, virally
safe,effective
Other Vit K
dependent
factors, risk of
thrombosis
Recombinant
FVIIa
>25000
15-30μg/kg
Very effective for
all indications, no
risk of viral
High cost
Surgery in FVII deficiency
 Several reports on surgical intervention under FVII replacement
have been published.
 A FVII level between 10-15IU/dl considered to be heamostatic
level.
 Neither a true minimum level nor the optimum duration of
factor substitution are well known.
 In the STER study have been shown that postoperative
haemostatic can be secured by rFVII a at a dose of at least
13μg/kg 3 times/day.
 In patients with FVII level < 1 IU/dl the mean duration
postoperative replacement was 5.8 .
‫از توجه شما سپاسگزارم‬