eMedicine Specialties > Pediatrics: General Medicine > Hematology
Factor VII Deficiency
Updated: Dec 11, 2007
Introduction
Background
Inherited factor VII (FVII) deficiency is a rare autosomal recessive hemorrhagic disorder. Clinical bleeding can widely vary and does not always correlate with the level of FVII coagulant activity measured in plasma.
FVII is one of the vitamin K–dependent coagulation factors synthesized in the liver. It is present in plasma in low concentrations (0.5 mcg/mL) and has a short circulating half-life of 3-4 hours. Plasma FVII predominantly exists in the form of the inactive single-chain zymogen; however, approximately 1% circulates in the activated form (FVIIa). Activation of FVII is the initiating event of in vivo coagulation. The ability of FVIIa to cleave other clotting factors depends on binding to its cofactor tissue factor (TF), which is expressed on the surface of endothelial cells and monocytes in response to injury or inflammation. With formation of the TF/VIIa complex, FVIIa rapidly activates clotting factors VII, IX, and X, initiating the coagulation cascade.
FVII plasma levels are influenced by both environmental and genetic factors. Dietary fat, age, obesity, and sex hormones influence FVII levels. Five identified allelic polymorphisms also affect plasma levels of FVII and FVIIa, with variations of as much as 25-30% in levels of activity and antigen.
Pathophysiology
Inherited FVII deficiency can be classified as type 1 or type 2, depending on the absence or presence of FVII antigen in plasma. Type 1 deficiencies result from decreased biosynthesis or accelerated clearance; type 2 abnormalities represent a dysfunctional molecule. More than 100 mutations, mostly missense mutations, have been identified in the FVII gene located on chromosome 13.1 Mutations have been identified throughout the gene, affecting all domains of the transcribed protein, most frequently the catalytic domain.Correlations between the factor VII genotype, FVII clotting activity and the clinical phenotype are not tight. Although individuals with the lowest FVII levels are most likely to be symptomatic, patients with identical mutations may have marked differences in clinical bleeding, suggesting that other factors may contribute to the clinical manifestations of FVII deficiency. Investigations to determine the contribution by FVII polymorphisms, other hemostatic proteins, and environmental factors have not yielded specific predictors of bleeding risk. At present, classification based on clinical history (age and type of presentation) rather than on FVII activity levels has proved to be more useful in predicting future risk of bleeding.
Frequency
United States
Inherited FVII deficiency is rare. Incidence is 1 case per 500,000 population.
International
The frequency is higher in countries where consanguineous marriage is more common. For example, the reported incidence of FVII deficiency in Iran is 3 times higher than that in the United Kingdom or Italy.2
Mortality/Morbidity
Mortality is related to severe bleeding, most often resulting from CNS hemorrhage.
Sex
FVII deficiency is autosomal recessive; the male-to-female ratio is 1:1. However, women are more likely to be symptomatic because of menorrhagia.
Age
Although this is a congenital disorder, the age at presentation varies widely, depending on the clinical severity; patients with CNS or gastrointestinal bleeds present at a younger age, often during infancy, and some in the neonatal period.
Clinical
History
Most severe cases of factor VII (FVII) deficiency are diagnosed during childhood, often during the first 6 months of life. In infancy, the most common bleeds occur in the gastrointestinal tract or CNS, accounting for 60-70% of bleeds in this age group. Spontaneous hemarthrosis also presents more frequently in children younger than 5 years (occurring in 20% of patients with FVII deficiency). These children usually have FVII levels of more than 2%.
The most common bleeding manifestations involve easy bruising and mucosal bleeding, particularly epistaxis or oral mucosal bleeding. Women are over represented among symptomatic patients because of menorrhagia (as high as 60%). Postoperative bleeding is also common, reported in association with 30% of surgical procedures, including procedures for which replacement therapy was administered.
Thrombosis in inherited FVII deficiency has been reported; most, but not all, cases are associated with the administration of FVIII replacement therapy and/or surgical procedures.
Physical
The physical manifestations are related to bleeding.
- Mucosal bleeding: Epistaxis and bleeding from the oral cavity or gastrointestinal tract have been observed.
- Menorrhagia and associated anemia
- Hemarthrosis: Patients with hemarthrosis have the same clinical presentation as those with hemophilia. Recurrent hemarthroses can lead to joint damage and chronic arthropathy.
- Bruising, soft tissue hematomas
- Neurological findings commensurate with CNS bleeding, particularly in infants
Causes
See Pathophysiology.
More on Factor VII Deficiency |
 Overview: Factor VII Deficiency |
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| Treatment & Medication: Factor VII Deficiency |
| Follow-up: Factor VII Deficiency |
| References |
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References
Mariani G, Herrmann FH, Dolce A, et al. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost. Mar 2005;93(3):481-7. [Medline].
Peyvandi F, Mannucci PM. Rare coagulation disorders. Thromb Haemost. Oct 1999;82(4):1207-14. [Medline].
Di Paola J, Nugent D, Young G. Current therapy for rare factor deficiencies. Haemophilia. Jan 2001;7 Suppl 1:16-22. [Medline].
Giansily-Blaizot M, Schved JF. Potential predictors of bleeding risk in inherited factorVII deficiency. Clinical, biological and molecular criteria. Thromb Haemost. Nov 2005;94(5):901-6. [Medline].
Mariani G, Dolce A, Marchetti G, Bernardi F. Clinical picture and management of congenital factor VII deficiency. Haemophilia. Oct 2004;10 Suppl 4:180-3. [Medline].
Mariani G, Lapecorella M, Dolce A. Steps towards an effective treatment strategy in congenital factor VII deficiency. Semin Hematol. Jan 2006;43(1 Suppl 1):S42-7. [Medline].
Perry DJ. Factor VII Deficiency. Br J Haematol. Sep 2002;118(3):689-700. [Medline].
Tuddenham EG, Pemberton S, Cooper DN. Inherited factor VII deficiency: genetics and molecular pathology. Thromb Haemost. Jul 1995;74(1):313-21. [Medline].
Further Reading
Keywords
inherited factor VII deficiency, FVII deficiency, vitamin K–dependent coagulation factors, hemorrhagic disorder, activated FVII, FVIIa, menorrhagia, hemarthrosis, thrombosis, epistaxis, anemia, hematoma
