Coagulation
Hereditary bleeding disorders
Factor XI 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 XI deficiency [title]

Cite this page: Factor XI deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/coagulationfactorXIdef.html. Accessed December 3rd, 2016.
Definition / General
  • Factor XI deficiency is a rare bleeding disorder that is inherited most commonly as an autosomal recessive trait, and is characterized by variable bleeding episodes
Sites
  • Bleeding into skin and mucosa, genitourinary tract, gastrointestinal tract (see clinical features below)
Pathophysiology
  • Factor XI is a serine protease that is produced in the liver, and is involved in the contact (intrinsic) pathway
  • It is activated by factor XIIa, thrombin or autoactivated, and activates factor IX, which in turn activates factor X to convert prothrombin to thrombin
  • Its biologic half-life is 60 - 80 hrs

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Coagulation cascade

Etiology
  • Most commonly inherited as an autosomal recessive trait
  • An autosomal dominant pattern of inheritance is possible, as the dimeric structure of factor XI may result in a dominant negative effect through intracellular heterodimer formation (Blood 2004;104:128)
  • The gene for factor XI is located on the long arm of chromosome 4
  • To date, over 180 mutations have been described with three main genotypes: type I are splice site mutations, type II are nonsense mutations and type III are missense mutations
  • Type II and III mutations are predominantly seen in Ashkenazi Jews
  • Type II mutations are also seen in Iraqi Jews and Israeli Arabs
Clinical Features
  • Deficiency can occur in homozygous, heterozygous or a combined heterozygous form
  • Bleeding manifestations do not correlate with factor XI levels
  • Most bleeding episodes in patients with severe deficiency are injury-related
  • Spontaneous bleeding is rare
  • May be associated with bruising, epistaxis, menorrhagia, GI / GU bleeding, umbilical stump bleeding or bleeding after surgery, trauma, dental procedures, pregnancy or circumcision
  • Up to 33% of patients with severe deficiency develop inhibitors after replacement therapy
Laboratory
  • Prolonged PTT that corrects with mixing study
  • Normal PT, thrombin time
  • Specific factor XI assay
Case Reports
Treatment
  • 10 - 20 ml fresh frozen plasma/kg, then 5 - 10 ml/kg every 24 hours as necessary
  • Antifibrinolytic therapy has been used in women with factor XI deficiency and menorrhagia
  • Patients with inhibitors have been treated successfully with plasma, prothrombin complex concentrates, and recombinant activated factor VII

  • Note: factor XI concentrates may promote thromboembolic complications
Differential Diagnosis