Home   Chapter Home   Jobs   Conferences   Fellowships   Books



Advertisement

Coagulation

Hereditary bleeding disorders

Factor VII deficiency


Reviewers: Kendall Crookston, M.D., Ph.D., University of New Mexico; Lizabeth Rosenbaum, M.D., University of New Mexico; Julie Gober-Wilcox, M.D., Resident, University of New Mexico (see Reviewers page)
Revised: 16 October 2010, last major update September 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Factor VII deficiency is a rare congenital bleeding disorder that is inherited as an autosomal recessive trait, and is characterized by variable bleeding symptoms, ranging from asymptomatic to life-threatening hemorrhage

Terminology
=========================================================================

● Also known as proconvertin deficiency
● The deficiency is classified as:
     -Type I: decreased synthesis or increased clearance (quantitative defect)
     -Type II: dysfunctional molecule (qualitative defect)

Pathophysiology
=========================================================================

● Factor VII is a vitamin K-dependent coagulation factor that is synthesized in the liver (Wikipedia)
● Circulating factor VII forms a complex with exposed tissue factor (from injured vascular endothelium), and is activated by proteases to initiate the extrinsic coagulation cascade to form a fibrin clot
● Biologic half-life is 3.5 hours

Coagulation cascade

Epidemiology
=========================================================================

● Factor VII deficiency is the most common of the rare congenital coagulation disorders
● Incidence is 1 in 500,000

Sites
=========================================================================

● Bleeding into skin and mucosa, joint and muscle, genitourinary tract, gastrointestinal tract, CNS (see clinical features below)

Etiology
=========================================================================

● Autosomal recessive inheritance
● More than 130 mutations have been described, predominantly missense and splice-site mutations and less commonly small deletion and nonsense mutations
● Other environmental and genetic factors influence phenotype since patients with identical factor VII gene mutations have been shown to have discordant bleeding severity

Clinical features
=========================================================================

● Patients with a homozygous or compound heterozygous genotype develop bleeding symptoms while heterozygotes are typically asymptomatic
● There is little correlation of factor levels and bleeding symptoms
● Patients exhibit easy bruising, epistaxis, soft tissue hematoma, menorrhagia, menometrorrhagia, postpartum bleeding, postoperative bleeding, hemarthrosis, retroperitoneal bleeding, gastrointestinal bleeding, intracranial hemorrhage
● Paradoxically, thrombotic episodes have been reported (e.g. deep venous thrombosis) in 3-4%, but in most cases, thrombotic risk factors were identified (Haemophilia 2008;14:564)
● Few cases have been reported of inhibitor development after replacement therapy

Laboratory
=========================================================================

● Prolonged PT
● Normal PTT (although may be prolonged)
● Obtain specific factor VII activity assay to confirm

Prognostic factors
=========================================================================

● Patients with severe deficiency typically have life-threatening bleeds (e.g. intracranial, gastrointestinal) within the first 6 months of life

Case reports
=========================================================================

● Multiple cerebral aneurysms in congenital factor VII deficiency (AJNR Am J Neuroradiol 2004;25:784)

Treatment
=========================================================================

● For mild hemorrhage, recommended to maintain factor levels of 5%-10% of normal to stop bleeding; for surgical procedures, recommended to maintain levels of 15%-20% of normal
● Recombinant factor VIIa is the treatment of choice; single dose for mild to moderate bleeding, or every 4-6 hours for severe bleeding episodes
● Due to the short half-life of factor VII (3.5 hr), it is difficult to give fresh frozen plasma (FFP) every 4-6 hours to maintain levels without producing volume overload
● Plasma derived factor VII concentrates and prothrombin complex concentrates are associated with post-treatment thrombosis

Differential diagnosis
=========================================================================

● Acquired factor VII deficiency (due to warfarin, vitamin K deficiency, severe liver disease)
● Acquired factor VII inhibitors
● Familial combined factor deficiencies (e.g. factor VI/factor VIII or factor II, VII, IX and X)

Additional references
=========================================================================

Semin Thromb Hemost 2009; 35:400, Haemophilia 2008;14:1170

End of Coagulation > Hereditary bleeding disorders > Factor VII deficiency


This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).