Factor VII Deficiency

Diagnosis and Management

Hamid Hoorfar MDInherited Blood Disorders Clinic

Esfahan Medical Sciences University2014

Introduction

• 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.(1-2% of zymogen)

• The factor VII gen is located on chromosome 13 upstream of factor X and contains 9 exons.

Congenital factor VII Deficiency The bleeding disorder was first described by Alexander in 1951.

Congenital FVII deficiency is the commonest among the rare inherited bleeding disorders with prevalence of 1 in 500000 individual.

It is an autosomal recessive disease . Bleedings is uncommon in FVII heterozygotes.

Complete absence of functional FVII is incompatible with life.

Numerous mutations underlying the disease have been described , which are predictive for a considerable heterogeneity in both clotting and clinical phenotypes.

Missense are most frequent mutations (70 -80%)

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 manifestationsIRF7 database (228 patients)

Symptomes No. %

Epistaxis 190 83

Easy bruising Gum bleedingMuscle hematomaHemarthrosis GastrointestinalHematuriaCNS bleeding Postoperative bleeding

14395575844261778

6242212214127

34

Clinical manifestationsIRF7 database (174 female)

Symptomes No. %

Epistaxis 98 56

Easy bruisingGum bleeding

Muscle hematomaHemarthrosisGI bleedingsHematuria

CNS bleedingsThrombosis

Postoperative bleedingsMenorrhagia

8359282824985

40100

4834161614553

3063

Diagnosis of Factor VII deficiencyA. Prolonged PT from moderate to markedly prolonged and normal

PTT

B. FVIIc is the confirmatory test for diagnosis

C. Factor VII deficiency has been found to be associated with hepatic congenital enzymic defects ( dubin – johnson and gilbert syndromes)

D. 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 costEasy 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 .

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