Factor I Deficiency

What is factor I (fibrinogen) deficiency?

Factor I (1) deficiency describes several conditions that involve problems with clotting factor I, a protein called fibrinogen. Fibrinogen gets converted during the process of blood clotting into another protein called fibrin, which is needed to form the mesh-like stable clot. Factor I deficiency affects about 1 in every million people.

Recently, an international organization (International Society on Thrombosis and Hemostasis) proposed a classification of fibrinogen deficiency severity based upon factor activity and associated symptoms, with a few exceptions.

  • Mild (> 1g/L): Patients are mostly asymptomatic, but might have problems with bleeding during trauma, a surgical procedure or with pregnancy/delivery
  • Moderate (0.1-1 g/L): Patients may have mild spontaneous bleeding, or bleeding triggered by trauma, surgery, or pregnancy/delivery
  • Severe (undetectable clot): Patients may have spontaneous, severe, and even life-threatening bleeding

Factor I deficiency includes several related disorders known as congenital fibrinogen defects. They comprise 2 disorders with little to no fibrinogen, a disorder where the fibrinogen is abnormal and doesn’t work the way it should, and a disorder where both of these are combined.

  • Afibrinogenemia - People with afibrinogenemia have no fibrinogen in their blood. Without fibrinogen, the body cannot make fibrin and a stable blood clot will not form.
  • Hypofibrinogenemia - People who have hypofibrinogenemia have lower than normal levels of fibrinogen. Without enough fibrinogen, the body cannot make fibrin and a stable clot will not form.
  • Dysfibrinogenemia -A person with dysfibrinogenemia has fibrinogen, but it does not work as it should.
  • Hypodysfibrinogenemia – This is a combined defect that involves both low levels of fibrinogen and impaired function of the small amount of fibrinogen that is produced.

What causes it?

Afibrinogenemia is a recessive disorder, meaning you have to inherit an affected gene from both parents. If you only have one gene you are a carrier and can pass it on to your children.

Hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia can be either recessive (both parents carry the gene and pass it to you to get the disease) or dominant (only one parent carries and transmits the gene for you to get it).

All types of factor I deficiency affect both males and females equally.

What are the symptoms?

A wide range of bleeding is seen in people with afibrinogenemia. They may have severe or even life-threatening bleeding or go years during which no bleeding occurs. Afibrinogenemia is often diagnosed in newborns. Common signs and symptoms include:

  • Umbilical cord bleeding
  • Swelling, pain, or warmth around a joint
  • Inability to straighten or bend a joint normally
  • Muscle, head, or neck ache
  • Tight and shiny appearance of skin
  • Bleeding into the skin
  • Upset stomach
  • Vomit that is black and syrupy or bright red or coffee ground in appearance
  • Difficulty with urination or bowel movements
  • Blood in the urine
  • Red- or black-colored stool
  • Drowsiness or loss of consciousness
  • Sensitivity to light
  • Weakness, tingling, or pain in the arms or legs
  • In women, heavy menstrual bleeding or recurrent miscarriage
  • Poor wound healing

Bleeding in people with hypofibrinogenemia is often mild. It may go undiagnosed until an episode of trauma or surgery. Common signs and symptoms include: 

  • In women, heavy menstrual bleeding
  • Muscle ache
  • Tight and shiny appearance of skin
  • Upset stomach
  • Vomit that is black and syrupy or bright red
  • Red- or black-colored stool

People with dysfibrinogenemia do not always have bleeding problems. In a study of 260 patients with dysfibrinogenemia, 55% of the patients had no complications, 25% had bleeding, and 20% had a tendency to get blood clots. A person is often diagnosed with dysfibrinogenemia after bleeding or having a blood clot, but the disease may go undiagnosed. Diagnosis often occurs in adulthood.

There is a wide range of signs and symptoms. Common signs and symptoms include:

  • Delayed wound healing
  • Rupture of surgical sutures
  • Dead or dying skin (necrosis)
  • In women, miscarriage, stillbirths, and excessive bleeding following childbirth
  • Blood clots

Symptoms of hypodysfibrinogenemia are variable and depend on the amount of fibrinogen that is produced and how it is functioning.

How is it diagnosed?

Factor I deficiency is diagnosed by a variety of blood tests, including screening blood tests for clotting problems. There is a specific test that measures the amount of fibrinogen in the blood. Low fibrinogen levels or abnormal function may also be the sign of another disease, such as liver or kidney disorders, so consultation with a specialist in bleeding disorders is important. Some of the common parameters used in measuring blood abnormalities like prothrombin time (PT), activated partial thromboplastin time (aPTT) or thrombin time (TT) are prolonged in congenital afibrinogenemia.

Very specific assays would need to be performed to differentiate between afibrinogenemia (no fibrinogen), hypofibrinogemia (low fibrinogen) and dysfibrinogenemia (abnormal fibrinogen). And this is why it is very important to see a hematologist who specializes in blood disorders.

How is it treated?

Replacement of fibrinogen through plasma-derived sources that contain fibrinogen is often required in those with afibrinogenemia, including in the case of spontaneous bleeding or surgical procedures. Treatment may also be given to prevent the formation of blood clots, as this complication can occur after replacement therapy.

Many people who have hypofibrinogenemia or dysfibrinogenemia may not need treatment.  Excessive menstrual bleeding in women with factor I deficiency may be controlled with hormonal therapy (oral or local) and drugs that prevent breakdown of blood clots (anti-fibrinolytic drugs). For women with factor I deficiency who want to get pregnant,  fibrinogen replacement therapy will help maintain pregnancy and reduce bleeding as well as prevents venous thrombosis and pregnancy loss.