Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the blood does not clot normally due to the lack of fibrinogen, a blood protein necessary for coagulation.[1] This disorder is autosomal recessive, meaning that two unaffected parents can have a child with the disorder.[2] The lack of fibrinogen expresses itself with excessive and, at times, uncontrollable bleeding.[3]
Contents
1Symptoms
2Causes
3Mechanism
4Diagnosis
4.1Diagnostic tests
5Treatment
6Prognosis
7History
8Current Research
9See also
10References
11External links
Symptoms
As this is a disorder that is present in an individual from birth, there are no warning signs to look for. The first symptom usually seen is hemorrhage from the umbilical cord that is difficult to stop.[2]
Other symptoms include:[4]
Nasal and oral mucosa bleeds
Gastrointestinal bleeding
Excessive/spontaneous bleeding or bruising from minor injury
Prolonged menstruation in women
Spontaneous abortion during pregnancy
CNS hemorrhaging[5]
Spontaneous bleeding of the mouth, nose, and gastrointestinal tract are common. Since blood clots can not be formed, minor injuries tend to lead to excessive bleeding or bruising. The biggest concern for individuals with afibrinogenemia is CNS hemorrhage, bleeding in the brain, which can be fatal.
Many of these symptoms are chronic, and will continue to occur for the entirety of the affected individual's life.
Causes
A missense or nonsense mutation to the genes that code for the fibrinogen protein are affected. Usually the mutation leads to an early stop in the production of the protein.[3] Due to the problem being genetically based, there is no way to prevent the disease. Individuals can get genetic testing done to see if they are a carrier of the trait, and if so may choose to complete genetic counseling to better understand the disorder and help manage family planning. Parents can choose to do prenatal genetic testing for the disorder to determine if their child will have the disease.[6] The only risk factor is if both parents of a child carry the recessive allele linked to the disorder.
Mechanism
Individuals with the disorder have a mutation to their fibrinogen gene that prevents the formation of the protein.[3] In normal conditions, fibrinogen is converted to fibrin when it is cleaved by the enzyme thrombin in the blood. The newly formed fibrin forms a fiber-rich network that helps trap red blood cells to start the coagulation process and form a clot.[7] Since there is no fibrinogen present during afibrinogenemia, fibrin can not be formed to aid in this process.
Diagnosis
Diagnostic tests
When a problem of fibrinogen is suspected, the following tests can be ordered:
PT[2]
PTT
Fibrinogen level in blood (total and clottable)
Reptilase time
Thrombin time[8]
Blood fibrinogen levels of less than 0.1 g/L and prolonged bleeding test times are indicators of an individual having afibrinogenemia.[2]
Treatment
The most common treatments are transfusions of cryoprecipitate or blood plasma to help with bleeding episodes or prior to surgery.[9] There are no known cures or forms of holistic care to date. Most complications arise from the symptoms of the disorder. [5]
Prognosis
As there is not much data out on the life expectancy of an individual with afibrinogenemia, it is difficult to determine the average lifespan. However, the leading cause of death thus far is linked to CNS hemorrhage and postoperative bleeding.[5]
History
It was first described in 1920 by German doctors, Fritz Rabe and Eugene Salomon, studying a bleeding disorder presenting itself in a child from birth.[10] This disorder may also be simply called afibrinogenemia or familial afibrinogenemia.[4] About 1 in 1 million individuals are diagnosed with the disease; typically at birth.[11] Both males and females seem to be affected equally,[2] but it has a higher occurrence in regions where consanguinity is prevalent.[4]
Current Research
Currently research is based in pharmacological treatments.[12] A case from 2015 was seen in which congenital afibrinogenemia was resolved in a patient after receiving a liver transplant.[13] Further research must be completed.
See also
Factor I Deficiency
References
^Neerman-Arbez, Marguerite; De Moerloose, Philippe (2007). "Mutations in the fibrinogen gene cluster accounting for congenital afibrinogenemia: An update and report of 10 novel mutations". Human Mutation. 28 (6): 540–53. doi:10.1002/humu.20483. PMID 17295221.
^ abcVu, Dung; Bolton-Maggs, Paula H. B.; Parr, Jeremy R.; Morris, Michael A.; Moerloose, Philippe de; Neerman-Arbez, Marguerite (2003-12-15). "Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion". Blood. 102 (13): 4413–4415. doi:10.1182/blood-2003-06-2141. ISSN 0006-4971. PMID 12893758.
^ abc"Afibrinogenemia | Disease | Your Questions Answered | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2015-11-12.
^Neerman-Arbez, Marguerite; Vu, Dung; Abu-Libdeh, Bassam; Bouchardy, Isabelle; Morris, Michael A. (2003-05-01). "Prenatal diagnosis for congenital afibrinogenemia caused by a novel nonsense mutation in the FGB gene in a Palestinian family". Blood. 101 (9): 3492–3494. doi:10.1182/blood-2002-10-3116. ISSN 0006-4971. PMID 12511408.
^"https://www.ebi.ac.uk/interpro/potm/2006_11/Page1.htm". www.ebi.ac.uk. Retrieved 2015-12-10. External link in |title= (help)
^Gallastegui, N.; Kimble, E. L.; Harrington, T. J. (2015-09-01). "Resolution of fibrinogen deficiency in a patient with congenital afibrinogenemia after liver transplantation". Haemophilia. 22 (1): e48–e51. doi:10.1111/hae.12802. ISSN 1365-2516. PMID 26421965.
External links
Classification
D
ICD-10: D68.2
ICD-9-CM: 286.3
OMIM: 202400
MeSH: D000347
DiseasesDB: 307
External resources
MedlinePlus: 001313
eMedicine: ped/3042
v
t
e
Diseases of clotting (D50–69,74, 280–287)
Coagulation/ coagulopathy
↑
Hyper- coagulability
primary: Antithrombin III deficiency
Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden
Prothrombin G20210A
Sticky platelet syndrome
acquired:Thrombocytosis
essential
DIC
Purpura fulminans
autoimmune
Antiphospholipid
↓
Hypo- coagulability
Thrombocytopenia
Thrombocytopenic purpura: ITP
Evans syndrome
TM
TTP
Upshaw Schulman syndrome
Heparin-induced thrombocytopenia
May–Hegglin anomaly
Platelet function
adhesion
Bernard–Soulier syndrome
aggregation
Glanzmann's thrombasthenia
platelet storage pool deficiency
Hermansky–Pudlak syndrome
Gray platelet syndrome
Clotting factor
Hemophilia
A/VIII
B/IX
C/XI
von Willebrand disease
Hypoprothrombinemia/II
Factor VII deficiency
Factor X deficiency
Factor XII deficiency
Factor XIII deficiency
Dysfibrinogenemia
Congenital afibrinogenemia
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
5. 血液製剤の病原体不活化 pathogen inactivation of blood products
English Journal
Correction to: Identification of novel mutations in congenital afibrinogenemia patients and molecular modeling of missense mutations in Pakistani population.
Naz A, Biswas A, Khan TN, Goodeve A, Ahmed N, Saqlain N, Ahmed S, Ujjan ID, Shamsi TS, Oldenburg J.
Thrombosis journal. 2019 ;17()5.
[This corrects the article DOI: 10.1186/s12959-017-0143-3.].
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is one of the inborn errors of immunity, characterized by impaired function of the regulatory T cells. Clinical manifestations of IPEX syndrome are characterized by various autoimmune diseases with autoantibodies. The co
Loss of fibrinogen in zebrafish results in an asymptomatic embryonic hemostatic defect and synthetic lethality with thrombocytopenia.
Hu Z, Lavik KI, Liu Y, Vo AH, Richter CE, Di Paola J, Shavit JA.
Journal of thrombosis and haemostasis : JTH. 2019 Apr;17(4)607-617.
Essentials Loss of fibrinogen in zebrafish has been previously shown to result in adult onset hemorrhage Hemostatic defects were discovered in early fga embryos but well tolerated until adulthood Afibrinogenemia and thrombocytopenia results in synthetic lethality in zebrafish. Testing human FGA vari
siRNA down-regulation of FGA mRNA in HepG2 cells demonstrated that heterozygous abnormality of the A alpha-chain gene does not affect the plasma fibrinogen level
Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238 bp deletion, and a compound heterozygous FGA1238 bp deletion and novel FGA c.54+3A>C substitution
International journal of hematology 96(1), 39-46, 2012-07-01
Congenital afibrinogenemia is a rare inherited blood disorder in which the blood does not clot normally due to a lack of or a malfunction involving fibrinogen, a protein necessary for coagulation. Fibrinogen is also known as Factor I. Its lack is ...
Congenital afibrinogenemia is a rare, inherited blood disorder in which the blood does not clot normally. It occurs when there is a complete lack (deficiency) of a protein called fibrinogen, which is needed for the blood to clot.
