Factor XI is part of the intrinsic pathway of blood coagulation. Factor XI deficiency leads to hemophilia C, which is a rare and relatively mild disorder with unpredictable bleeding tendencies. The function of the factor, and the pathology of the disease are incompletely understood.
Factor XI functions as a serine protease and activates factor IX, which, together with factor VIII activates factor X. Factor XI also acts to decrease fibrinolysis , and may have a role in inflammatory processes. The protein circulates as a homodimer, and dimerization is required for secretion into the bloodstream.
Deficiency of factor XI has a high incidence of occurrence in people of Ashkenazi Jewish heritage. In this population, there are two prevalent mutations, one substituting for an amino acid, and another resulting in premature chain termination. As may be expected, people homozygous for the nonsense mutation tend to bleed more extensively than those with the missense mutation. However, in most other cases the severity of the disease is not well correlated with genotype or with residual amount or activity of the protein   , possibly owing to aberrant interactions between factor XI and other coagulation factors when those are at suboptimal levels . For example, members of the same family with similar factor XI deficiency were found with incongruous symptoms . The disease is normally inherited in a recessive manner. However, some mutant proteins can bind normal monomers in heterodimer structures that cannot be secreted. In a situation like this, the secretion of the normal protein is prevented in a heterozygote, and the inheritance becomes dominant .
Spontaneous bleeding in factor XI deficiency is very rare, as is bruising or hemarthrosis. Unusual bleeding usually follows trauma, such as circumcision, dental work, tonsillectomy or other surgeries, but there is a tendency for it to occur mainly in the mouth and genitourinary systems, where fibrinolytic activity is high. This may be explained by the role of factor XI in inhibiting fibrinolysis. Menorrhagia and postpartum bleeding are frequent signs of factor XI deficiency. In some cases, a family history of a mild bleeding disorder may be a sign of the deficiency. In other cases, factor XI deficiency may be discovered during follow-up of an incidental finding of prolonged activated partial thromboplastin time (aPTT), which is measured routinely before surgeries. Factor XI deficiency may be acquired as a consequence of systemic lupus erythematosus. The levels of factor XI will decrease, together with many other proteins, when liver function is compromised.
A suspicion of coagulopathy calls for the usual coagulation tests, which comprise the prothrombin time (PT), (APTT), and fibrinogen level. If a prolonged APTT result is obtained, mixing studies with normal plasma are usually performed to determine whether the anomaly is due to deficiency of a factor, or to the presence of an inhibitor. This determination has obvious implications for therapy. More than a quarter of the patients with a severe factor XI deficiency harbor an inhibitor to the factor , and very small amounts of factor XI in blood-derived preparations have been shown to trigger formation of the inhibitor . In interpreting the APTT test results, the variability of different testing agents should be kept in mind. On the one hand, some reagents are oversensitive to lupus anticoagulant antibodies, and therefore may show false positive results. On the other hand, the sensitivity of some test reagents may be too low so that false negative results will be observed . People with bleeding abnormalities should undergo tests with individual clotting factors.
Homozygotes, or people with two differently affected alleles (compound heterozygotes), usually have less than 10% of normal factor XI levels, whereas heterozygotes have about 50%.
Prognosis Prognosis is good, as bleeding symptoms are usually moderate. The documents contained in this web site are presented for information purposes only. [orpha.net]
FFP transfusion prior to surgery may help patients’ coagulation, and proper anesthetic management, including peripheral nerve block, may contribute to improved prognosis. [jaclinicalreports.springeropen.com]
Etiology Congenital FXI deficiency is caused by mutations in the F11 gene (4q35) controlling the production of plasma FXI. Unlike in most factor deficiencies, the severity of the bleeding manifestations is poorly correlated with the FXI level. [orpha.net]
[…] 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 Images hosted on other servers: Coagulation cascade Etiology [pathologyoutlines.com]
Format for individual disorder discussions includes 1) background, 2) pathophysiology, 3) etiology, 4) signs and symptoms, 5) diagnoses, 6) possible related complications/disorders, and 7) treatments/research. UNIQUE! [books.google.ro]
Summary Epidemiology Prevalence of homozygous forms is estimated at 1/1,000,000. The disease is more frequent in the Jewish population. The frequency of partial deficiency among Ashkenazy Jews is 8%. [orpha.net]
Epidemiologic data has shown that high levels of FXI are associated with an increased risk of venous thrombosis. Deficiency of FXI does not protect from myocardial infarction. It is not known if low levels of FXI protect from venous thrombosis. [emedicine.medscape.com]
Understanding the pathophysiology and clinical significance of this disease entity can help avoid potentially hazardous sequelae. [ncbi.nlm.nih.gov]
Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children. [books.google.com]
In animal models, targeting FXI by knocking out the gene or by using FXI-neutralizing antibodies, antisense oligonucleotides, and peptidomimetic inhibitors, prevents arterial and vein thrombosis. [ncbi.nlm.nih.gov]
A multidisciplinary approach along with an individual care plan is recommended to prevent bleeding complications. [thieme-connect.com]
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