Coagulation
Hereditary bleeding disorders
Factor XIII deficiency

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

Revised: 28 April 2016, last major update July 2011

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Factor XIII deficiency

Cite this page: Factor XIII deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/coagulationfactorXIIIdef.html. Accessed December 4th, 2016.
Definition / General
  • Factor XIII deficiency is a congenital disorder that is inherited as an autosomal recessive trait and is associated with a variable bleeding tendency
  • Acquired factor XIII deficiency is associated with liver failure, inflammatory bowel disease, leukemia, disseminated intravascular coagulation, Henoch-Schonlein purpura, systemic lupus erythematosus and exposure to certain drugs (phenytoin, isoniazid, valproate)
Terminology
  • Factor XIII is also known as fibrin stabilizing factor
Epidemiology
  • Estimated at 1 in 2 to 5 million births
  • More frequent in regions where consanguineous marriages are more common
Sites
  • Skin and mucosa, joints, soft tissue, gastrointestinal tract, genitourinary tract, CNS (see clinical features below)
Pathophysiology
  • Factor XIII is a transglutaminase that circulates as a zymogen comprised of 2 catalytic A subunits and 2 carrier B subunits
  • The A subunit is synthesized in platelets, monocytes and macrophages while the B subunit is synthesized in the liver; the A and B dimers then assemble in the plasma to form a heterotetramer
  • Factor XIII is activated by thrombin and is responsible for catalyzing the final step in the coagulation cascade by cross-linking fibrin (in the presence of calcium)
  • Deficiency is due to a defect in either the A gene (type 2) or B gene (type 1)

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Diagram of factor XIII activation

Etiology
  • Inherited as an autosomal recessive trait
  • Most cases are due to mutations in A subunit gene on chromosome 6
  • More than 70 mutations have been identified, most of which are missense and nonsense mutations
  • Only 5 mutations in FXIII B deficient patients have been identified; gene is on chromosome 1
Clinical Features
  • Variable bleeding tendency, from mild to severe depending on factor levels
  • Umbilical cord stump bleeding, intracranial hemorrhage, soft tissue hematoma, bleeding after circumcision, gastrointestinal bleeding, gingival bleeding, epistaxis, hematuria, surgical site bleeding, menorrhagia, joint bleeding, delayed healing, spontaneous abortion, recurrent miscarriage
  • Plasma half life is 9 - 12 days
  • Factor XIII levels above 3 - 5% are usually sufficient to prevent spontaneous bleeding
  • Severe bleeding typically occurs in individuals with < 1% circulating levels
  • Compound heterozygotes are usually asymptomatic
Laboratory
  • Normal PT, PTT, thrombin time, fibrinogen
  • Screening test for factor XIII deficiency uses the clot solubility test in which patient plasma is incubated with thrombin and calcium; deficiency will cause the clot to dissolve in the presence of urea or acid
  • A standard mixing test using patient plasma and normal pooled plasma is usually performed to rule out the presence of an inhibitor
  • Confirmatory testing uses a quantitative factor XIII activity assay
Prognostic Factors
  • Although there is a life-long risk of bleeding, prognosis is excellent due to good response to treatment; subsequent risk of development of inhibitors is low
Case Reports
Treatment
  • Factor XIII concentrate, FFP or cryoprecipitate for replacement therapy or for treatment of acute bleeding episodes:
  • Factor XIII concentrate: 10 - 20 U/kg at 4 - 6 week intervals
  • FFP: 10 mL/kg every 4 - 6 weeks
  • Cryoprecipitate: 1 bag per 10 - 20 kg every 3 - 4 weeks
  • To prevent miscarriage, maintain factor XIII levels > 10% in early gestation and > 30% at time of delivery to prevent significant bleeds
Differential Diagnosis
  • Acquired factor XIII deficiency