Coagulation
Hereditary bleeding disorders
Factor X 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 October 2010

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PubMed Search: Factor X deficiency

Cite this page: Factor X deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/coagulationfactorXdef.html. Accessed December 9th, 2016.
Definition / General
  • Factor X deficiency is a rare congenital bleeding disorder that is inherited as an autosomal recessive trait, and is characterized by a variable bleeding tendency
Terminology
  • Also known as Stuart-Prower Factor Deficiency

  • Deficiency classified as either:
    • Type I: decreased functional activity and antigen level (quantitative defect)
    • Type II: decreased functional activity and near normal antigen level (qualitative defect)
Epidemiology
  • Estimated incidence of 1 in 500,000 to 1,000,000; however, in countries where consanguinity is more common (e.g. Iran), incidence is reported to be 1 in 200,000
  • Estimated carrier incidence of 1 in 500
Sites
  • Bleeding into skin and mucosa, joint and muscle, genitourinary tract, gastrointestinal tract, CNS (see clinical features below)
Pathophysiology
  • Factor X is a vitamin K-dependent serine protease produced in the liver
  • It is the first enzyme in the common pathway to form a fibrin clot
  • Its activated form (in complex with factor Va, Ca++ and phospholipid) cleaves prothrombin to thrombin
  • It has a long half-life of 20 - 40 hours

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Coagulation cascade

Etiology
  • Inherited as an autosomal recessive trait
  • More than 80 mutations have been identified, which include small deletions, missense and frameshift mutations
Clinical Features
  • May be associated with bruising, epistaxis, menorrhagia, GI / GU bleeding, umbilical stump bleeding or bleeding after surgery, trauma, dental procedures, pregnancy or circumcision, recurrent fetal loss
  • Bleeding symptoms in severe deficiency are similar to that seen in patients with factor VIII (hemophilia A) and factor IX (hemophilia B) deficiency
  • Heterozygotes are usually asymptomatic but may have mild mucocutaneous bleeds
  • Patients with severe deficiency are either homozygous or compound heterozygous
  • Bleeding symptoms tend to correlate with factor X activity levels: mild (> 6% - 10%), moderate (1% - 5%) or severe (< 1%)
  • A small percentage of patients develop factor X inhibitors with factor replacement therapy
Laboratory
  • Prolonged PT and PTT that correct with mixing study
  • Prolonged Russells viper venom time (measures the direct activation of factor X)
  • Normal thrombin and bleeding time
  • Factor X specific functional and immunologic assays for confirmation
Prognostic Factors
  • Particular genotypes [Gly(- 20)Arg, Gly94Arg and Gly380Arg mutations] are associated with higher rates of hemarthrosis and intracranial bleeding
Case Reports
Treatment
  • For minor bleeding episodes, maintain factor X levels at 10% - 15% of normal using FFP (15 - 20 mL/kg followed by 3 - 6 mL/kg every 24 hours)
  • For major bleeding episodes, trauma or surgical procedures, factor X rich prothrombin complex concentrates can be used to maintain factor X levels at 50% of normal
Differential Diagnosis
  • Acquired factor X deficiency (liver disease, vitamin K deficiency): also exhibits reduced levels of other coagulation factors; isolated factor X deficiency is associated with respiratory infection, AML and other malignancies, amyloidosis
  • Acquired factor X inhibitors in patients without congenital factor X deficiency are rare but have been reported in leprosy and chemical exposure
  • Other factor deficiencies: e.g. factor V, prothrombin