Congenital afibrinogenemia
Rare inherited disorder causing uncontrollable bleeding due to fibrinogen deficiency.
Congenital afibrinogenemia is a rare inherited blood disorder where the body cannot produce fibrinogen, a protein essential for normal blood clotting. Because it follows an autosomal recessive pattern, a child can inherit the condition even if both parents show no symptoms. The absence of fibrinogen leads to excessive and sometimes uncontrollable bleeding.
**Signs and symptoms** Since the disorder is present from birth, the first noticeable symptom is often difficult-to-stop bleeding from the umbilical cord. Other symptoms include bleeding from the nose and mouth, gastrointestinal bleeding, easy or spontaneous bruising and bleeding from minor injuries, prolonged menstrual periods, miscarriage during pregnancy, and bleeding in the central nervous system.
**Causes** The condition results from a missense or nonsense mutation in the genes responsible for producing fibrinogen. These mutations typically cause an early halt in protein production. Because the disorder is genetic, it cannot be prevented. Genetic testing can identify carriers, and those who test positive may choose genetic counseling to better understand the condition and plan their families. Prenatal genetic testing is also available to determine if a child will be affected.
**Mechanism** In people with this disorder, a mutation in the fibrinogen gene prevents the protein from being formed. Normally, the enzyme thrombin converts fibrinogen into fibrin, which then creates a fiber network that traps red blood cells and forms a stable clot. Without fibrinogen, this process cannot happen.
**Diagnosis** When a fibrinogen problem is suspected, doctors may order tests such as prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level (total and clottable), reptilase time, and thrombin time. Blood fibrinogen levels below 0.1 g/L, along with prolonged bleeding times, point to afibrinogenemia. A platelet aggregation function test may also raise suspicion of the condition.
**Treatment** The main treatment is fibrinogen replacement therapy, which includes transfusions of cryoprecipitate, blood plasma, or fibrinogen concentrate to manage bleeding episodes or prepare for surgery. While some thrombotic complications have been reported after replacement therapy, fibrinogen concentrate is generally considered the best option.
- Field
- Hematology
- Known for
- Rare inherited bleeding disorder caused by lack of fibrinogen
- Prevalence
- About 1 in 1 million individuals
- Inheritance
- Autosomal recessive
- First described
- 1920 by German doctors Fritz Rabe and Eugene Salomon
Lore & Background
Congenital afibrinogenemia was first described in 1920 by German doctors Fritz Rabe and Eugene Salomon, studying a bleeding disorder presenting itself in a child from birth. The disorder may also be called afibrinogenemia or familial afibrinogenemia. It is caused by a missense or nonsense mutation to the genes that code for the fibrinogen protein, usually leading to an early stop in the production of the protein. Individuals with the disorder have a mutation that prevents the formation of fibrinogen, which in normal conditions is converted to fibrin by the enzyme thrombin to form a clot.
Reader's Guide
Congenital afibrinogenemia is significant as a rare genetic disorder that highlights the critical role of fibrinogen in blood coagulation. Its autosomal recessive inheritance pattern means two unaffected parents can have an affected child, and it has a higher occurrence in regions where consanguinity is prevalent. Diagnosis relies on blood tests showing fibrinogen levels less than 0.1 g/L and prolonged bleeding times. Treatment centers on fibrinogen replacement therapy, with fibrinogen concentrate considered most beneficial due to its purity and lower risk of allergic reaction. The leading cause of death is CNS hemorrhage and postoperative bleeding. A 2015 case showed resolution after a liver transplant, pointing to potential future treatments.
Did You Know?
- The first symptom usually seen is hemorrhage from the umbilical cord that is difficult to stop.
- Blood fibrinogen levels of less than 0.1 g/L are indicators of afibrinogenemia.
- A 2015 case saw congenital afibrinogenemia resolved in a patient after receiving a liver transplant.
- Both males and females seem to be affected equally.
More in Congenital disorders 1-24
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