Coagulation
Hereditary bleeding disorders
Factor VII deficiency

Authors: Kendall Crookston, M.D., Ph.D., Lizabeth Rosenbaum, M.D. and Julie Gober-Wilcox, M.D. (see Authors page)

Revised: 28 April 2016, last major update September 2010

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PubMed Search: Factor VII deficiency [title]

Definition / General
  • 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
Epidemiology
  • Factor VII deficiency is the most common of the rare congenital coagulation disorders
  • Incidence is 1 in 500,000
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)
Sites
  • Bleeding into skin and mucosa, joint and muscle, genitourinary tract, gastrointestinal tract, CNS (see clinical features below)
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

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Coagulation cascade

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
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