Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

does not clot normally due to the lack of

fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

, a blood

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

necessary for

coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...

. This disorder is

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

, meaning that two unaffected parents can have a child with the disorder. The lack of fibrinogen expresses itself with excessive and, at times, uncontrollable bleeding.

Signs and 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 Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

from the umbilical cord that is difficult to stop. Other symptoms include: * Nasal and oral

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

bleeds *

Gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

bleeding * Excessive/spontaneous bleeding or bruising from minor injury * Prolonged

menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...

in women *

Spontaneous abortion Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can survive independently. Miscarriage before 6 weeks of gestation is ...

during pregnancy * CNS hemorrhaging

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. Due to the problem being genetically based, there is no way to prevent the disease. Individuals can get

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

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.

Mechanism

Individuals with the disorder have a mutation to their fibrinogen gene that prevents the formation of the protein. In normal conditions, fibrinogen is converted to

fibrin Fibrin (also called Factor Ia) is a fibrous protein, fibrous, non-globular protein involved in the Coagulation, clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerization, polymerize. ...

when it is cleaved by the enzyme

thrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

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.

Diagnosis

Diagnostic tests

When a problem of fibrinogen is suspected, the following tests can be ordered: * PT * PTT *

Fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

level in blood (total and clottable) *

Reptilase time Reptilase time (RT) is a blood test used to detect deficiency or abnormalities in fibrinogen, especially in cases of heparin contamination. Reptilase, an enzyme found in the venom of Bothrops snakes, has activity similar to thrombin. Unlike th ...

Thrombin time The thrombin time (TT), also known as the thrombin clotting time (TCT), is a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added. It is ...

Blood fibrinogen levels of less than 0.1 g/L and prolonged bleeding test times are indicators of an individual having afibrinogenemia. A suspicion of congenital afibrinogenemia may appear on a platelet aggregation function test.

Treatment

The most common treatment is fibrinogen replacement therapy, including

cryoprecipitate Cryoprecipitate, also called cryo for short, or Cryoprecipitate Antihemophilic factor (AHF), is a frozen blood product prepared from blood plasma. To create cryoprecipitate, plasma is slowly thawed to 1–6 °C. A cold-insoluble precipita ...

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

, and fibrinogen concentration transfusions to help with bleeding episodes or prior to surgery. Although some thrombotic complications have been reported following replacement therapy, transfusions of fibrinogen concentrate are widely considered to be the most beneficial. Fibrinogen concentrate is pure, contains a known quantity of fibrinogen, is virally inactivated, and is transfused in small amounts. There is a lower chance of allergic reaction in response to transfusion. Alternatively, cryoprecipitate contains other coagulation factors, factors VIII, XIII, and von Willebrand factor. There are no known cures or forms of holistic care to date. Most complications arise from the symptoms of the disorder.

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.

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. This disorder may also be simply called afibrinogenemia or familial afibrinogenemia. About 1 in 1 million individuals are diagnosed with the disease; typically at birth. Both males and females seem to be affected equally, but it has a higher occurrence in regions where

consanguinity Consanguinity (from Latin '':wikt: consanguinitas, consanguinitas'' 'blood relationship') is the characteristic of having a kinship with a relative who is descended from a common ancestor. Many jurisdictions have laws prohibiting people who are ...

is prevalent.

Research

Currently research is based in pharmacological treatments. A case from 2015 was seen in which congenital afibrinogenemia was resolved in a patient after receiving a liver transplant.

References

External links

{{Diseases of megakaryocytes, us=y Coagulopathies Congenital disorders