Congenital fibrinogen deficiency (CFD) is one of the rarest bleeding disorders. The most severe form of CFD affects just one or two people in a million. Yet for children and adults living with the condition, it presents a complex set of challenges — severe and life-threatening bleeding, a paradoxical risk of dangerous blood clots, and symptoms that can vary widely, even among individuals with the same genetic mutation.
The good news is that the treatment landscape for CFD has expanded considerably in recent years: There are now three approved therapies on the market, and experts have published guidelines for managing pregnancy in CFD. Below are answers to some of the most commonly asked questions about CFD.
What is congenital fibrinogen deficiency?
Congenital fibrinogen deficiency is a group of inherited bleeding disorders that occur when the body either lacks the critical clotting protein fibrinogen, produces too little of it, or makes a version that doesn’t work properly.
Fibrinogen (also known as factor I) is one of the key building blocks of the blood clotting process. Its primary role is to convert into fibrin, which is a sticky, thread-like protein that acts as a structural mesh to trap platelets and red blood cells and help form a strong, stable blood clot.
When fibrinogen is missing completely, in short supply, or works improperly, the body may have difficulty stopping bleeding after an injury, surgery, or childbirth. In severe cases, people can experience a potentially life-threatening hemorrhage.
Together, CFD disorders account for about 8% of all rare bleeding disorders worldwide.
What are the symptoms of congenital fibrinogen deficiency?
Symptoms of CFD can vary widely. Common symptoms include:
- Umbilical cord bleeding in babies
- Bruising
- Frequent nosebleeds
- Heavy menstrual bleeding
- Joint or muscle bleeds
- Prolonged bleeding after an injury, surgery, or childbirth
Less commonly, CFD can cause bleeding in the digestive tract or brain. Women with CFD are also at increased risk of miscarriage and bleeding during pregnancy and delivery.
What are the types of congenital fibrinogen deficiency?
CFD is not a single disease but a spectrum of related subtypes, classified according to how fibrinogen quantity and function are affected.
Afibrinogenemia
Afibrinogenemia is the most severe form of CFD. Circulating fibrinogen is completely absent. It is inherited in an autosomal recessive pattern, meaning a child must inherit defective copies of the gene from both parents. This is the subtype most likely to cause serious bleeding from early infancy onward, and many newborns are diagnosed when they have prolonged umbilical cord bleeding shortly after birth. Bleeds can also occur in the skin, gastrointestinal tract, genitourinary tract, and, less frequently, the central nervous system. This subtype is also associated with an increased risk of thrombosis, which is when a blood clot forms inside a blood vessel and blocks or slows the natural flow of blood.
Hypofibrinogenemia
Hypofibrinogenemia involves reduced but not absent fibrinogen levels, with severity depending on how low levels fall. The condition may be inherited from one or both parents. Some people are diagnosed in infancy, but others don’t discover the disorder until abnormal bleeding occurs during surgery, trauma, or childbirth later in life. The risk of thrombosis is lower with this subtype.
Dysfibrinogenemia
Dysfibrinogenemia is what is known as a qualitative defect. While fibrinogen is present at normal or near-normal levels, it’s structurally abnormal and can’t perform its clotting function properly. In many cases, dysfibrinogenemia may not cause any symptoms. This subtype also carries an increased risk of thrombosis.
How is congenital fibrinogen deficiency diagnosed?
Doctors diagnose CFD using blood tests that measure the amount of fibrinogen in the blood and how well fibrinogen functions. If those tests suggest CFD, genetic testing can identify genetic changes to confirm the diagnosis and determine the specific type of the disorder.
There is no strong correlation between genotype and the severity of CFD. Two people who have the same genetic mutation can often have very different symptoms.
How is congenital fibrinogen deficiency treated?
The cornerstone of treatment for acute bleeding in afibrinogenemia and hypofibrinogenemia is fibrinogen replacement therapy, and there are three medications approved by the Food and Drug Administration (FDA) on the market: RiaSTAP, Fibryga, and Fesilty. All three products are given intravenously.
None of the approved therapies are indicated for dysfibrinogenemia, because of an increased risk of thrombosis. This type of CFD is usually treated with either fresh frozen plasma or cryoprecipitate.
How should pregnancy be managed in women with a congenital fibrinogen deficiency disorder?
In 2024, an expert panel from the International Society on Thrombosis and Haemostasis published the first guidelines on managing pregnancy, delivery, and the postpartum period in CFD. The guidelines emphasize the importance of closely monitoring fibrinogen levels and replacing it at specific points to protect against bleeding while allowing safer use of pain management options such as epidurals.