Factor VII Deficiency Diagnosis and Management Hamid Hoorfar MD Inherited Blood Disorders Clinic Esfahan Medical Sciences University 2014

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 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 24 9 8 5 40 100 48 34 16 14 3 30 63

Diagnosis of Factor VII deficiency Prolonged PT from moderate to markedly prolonged and normal PTT FVIIc is the confirmatory test for diagnosis Factor VII deficiency has been found to be associated with hepatic congenital enzymic defects ( dubin – johnson and gilbert syndromes) 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 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