Congenital hypofibrinogenemia: Difference between revisions
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'''Congenital hypofibrinogenemia''' is a disorder in which one of the two genes responsible for producing [[fibrinogen]] |
'''Congenital hypofibrinogenemia''' is a rare disorder in which one of the two genes responsible for producing the [[fibrinogen]], a critical [[blood clotting factor]], is unable to make functional fibrinogen [[protein]] because of an inherited [[mutation]]. In consequence, liver cells, the normal site of fibrinogen production, make small amounts of this critical [[coagulation]] protein, blood levels of fibrinogen are low, and individuals with the disorder may suffer a [[coagulopathy]], i.e. a [[diathesis]] or propensity to experience episodes of abnormal bleeding. However, individuals with congenital hypofibringenemia may also suffer episodes of abnormal blood clot formation, i.e. [[thrombosis]]. This seemingly paradoxical propensity to develop thrombosis in a disorder causing a decrease in a critical protein for blood clotting may be due to the function of [[fibrin]] (the split product of fibrinogen that is the basis for forming blood clots) to promote the [[lysis]] or desolution of blood clots.<ref name="pmid27019462">{{cite journal | vauthors = Casini A, de Moerloose P, Neerman-Arbez M | title = Clinical Features and Management of Congenital Fibrinogen Deficiencies | journal = Seminars in Thrombosis and Hemostasis | volume = 42 | issue = 4 | pages = 366–74 | year = 2016 | pmid = 27019462 | doi = 10.1055/s-0036-1571339 | url = }}</ref> |
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Congenital hypofibrinogenemia must be distinguished from: '''a)''' [[congenital afibrinogenemia]], a rare disorder in which blood fibrinogen levels are either exceedingly low or undetectable due to mutations in both fibrinogen genes; '''b)''' [[Hypodysfibrinogenemia|congenital hypodysfibrinogenemia]], a rare disorder in which one or more genetic mutations cause low levels of blood fibrinogen, at least some of which is dysfunctional and thereby contributes to excessive bleeding; and '''c)''' acquired hypofibrinogenemia, a non-hereditary disorder in which blood fibrinogen levels are low because of e.g. severe liver disease or in which blood fibrinogen levels are low because of excessive consumption resulting from, e.g. [[disseminated intravascular coagulation]].<ref name="pmid27019462"/><ref name="pmid27713652">{{cite journal | vauthors = Besser MW, MacDonald SG | title = Acquired hypofibrinogenemia: current perspectives | journal = Journal of Blood Medicine | volume = 7 | issue = | pages = 217–225 | year = 2016 | pmid = 27713652 | doi = 10.2147/JBM.S90693 | url = }}</ref> |
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Certain gene mutations causing congenital hypfibrinogenemia disrupt the ability of liver cells to secrete fibrinogen. In these instances, the un-mutated gene maintains blood fibrinogen at reduce levels but the mutated gene produces a fibrinogen that accumulates in liver cells sometimes to such extents that it becomes toxic. In the latter cases, sever liver disease may ensue in a syndrome termed '''fibrinogen storage disease.'''<ref name="pmid25990487">{{cite journal | vauthors = Casini A, Sokollik C, Lukowski SW, Lurz E, Rieubland C, de Moerloose P, Neerman-Arbez M | title = Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature | journal = Haemophilia : the Official Journal of the World Federation of Hemophilia | volume = 21 | issue = 6 | pages = 820–7 | year = 2015 | pmid = 25990487 | doi = 10.1111/hae.12719 | url = }}</ref> |
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== References == |
== References == |
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Revision as of 16:58, 11 September 2017
Congenital hypofibrinogenemia is a rare disorder in which one of the two genes responsible for producing the fibrinogen, a critical blood clotting factor, is unable to make functional fibrinogen protein because of an inherited mutation. In consequence, liver cells, the normal site of fibrinogen production, make small amounts of this critical coagulation protein, blood levels of fibrinogen are low, and individuals with the disorder may suffer a coagulopathy, i.e. a diathesis or propensity to experience episodes of abnormal bleeding. However, individuals with congenital hypofibringenemia may also suffer episodes of abnormal blood clot formation, i.e. thrombosis. This seemingly paradoxical propensity to develop thrombosis in a disorder causing a decrease in a critical protein for blood clotting may be due to the function of fibrin (the split product of fibrinogen that is the basis for forming blood clots) to promote the lysis or desolution of blood clots.[1]
Congenital hypofibrinogenemia must be distinguished from: a) congenital afibrinogenemia, a rare disorder in which blood fibrinogen levels are either exceedingly low or undetectable due to mutations in both fibrinogen genes; b) congenital hypodysfibrinogenemia, a rare disorder in which one or more genetic mutations cause low levels of blood fibrinogen, at least some of which is dysfunctional and thereby contributes to excessive bleeding; and c) acquired hypofibrinogenemia, a non-hereditary disorder in which blood fibrinogen levels are low because of e.g. severe liver disease or in which blood fibrinogen levels are low because of excessive consumption resulting from, e.g. disseminated intravascular coagulation.[1][2]
Certain gene mutations causing congenital hypfibrinogenemia disrupt the ability of liver cells to secrete fibrinogen. In these instances, the un-mutated gene maintains blood fibrinogen at reduce levels but the mutated gene produces a fibrinogen that accumulates in liver cells sometimes to such extents that it becomes toxic. In the latter cases, sever liver disease may ensue in a syndrome termed fibrinogen storage disease.[3]
References
- ^ a b Casini A, de Moerloose P, Neerman-Arbez M (2016). "Clinical Features and Management of Congenital Fibrinogen Deficiencies". Seminars in Thrombosis and Hemostasis. 42 (4): 366–74. doi:10.1055/s-0036-1571339. PMID 27019462.
- ^ Besser MW, MacDonald SG (2016). "Acquired hypofibrinogenemia: current perspectives". Journal of Blood Medicine. 7: 217–225. doi:10.2147/JBM.S90693. PMID 27713652.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Casini A, Sokollik C, Lukowski SW, Lurz E, Rieubland C, de Moerloose P, Neerman-Arbez M (2015). "Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature". Haemophilia : the Official Journal of the World Federation of Hemophilia. 21 (6): 820–7. doi:10.1111/hae.12719. PMID 25990487.