Congenital Factor VII Deficiency
What is Congenital Factor VII Deficiency?
Your body takes a series of complex steps to stop bleeding. It begins with blood vessels constricting (narrowing) and platelets forming a plug in the vessel wall where it is injured. This starts a process called clotting, in which a group of proteins works (referred to as factors) work together to create a firm blood clot. The process of forming a blood clot involves a series of steps that result in a net like structure called fibrin. This net makes the blood clot stable and stops the bleeding until the vessel wall can heal.
Factor VII (7) is one of the proteins that plays a role in helping your blood clot. Factor VII binds to tissue factor at the site of injury to the blood vessel wall to generate thrombin, which is necessary to make the fibrin.
1. Upon vessel injury, tissue factor (TF) is exposed to circulating factor VII (FVII) and activated factor VII (FVIIa). The TF-FVII complex initiates coagulation and leads to generation of small amounts of thrombin.
2. Various simultaneous reactions and activation of clotting factors leads to the "thrombin burst", which is proceeded by formation of a stabilized clot.
Congenital factor VII deficiency is a bleeding disorder in which there are low levels of factor VII in the blood. Congenital factor VII deficiency is rare, affecting an estimated 1 in every 500,000 people. Males and females are equally affected.
Factor VII levels in the blood can be measured with a factor VII assay test. Normal factor VII levels are between 50% and 200%. Generally, patients with lower factor VII levels tend to have more symptoms, although there isn’t an exact correlation like there is in congenital hemophilia (factor VIII  or IX  deficiency).
Recently, the International Society of Thrombosis and Hemostasis (ISTH) proposed a new classification of congenital factor VII deficiency severity based upon patterns of symptoms and factors levels seen in studies of patients with rare disorders:
- Mild (>20% activity): Patients are mostly asymptomatic (usually do not have symptoms), but might have problems with bleeding during trauma, a surgical procedure or with pregnancy/delivery
- Moderate (10-20% activity): Patients may have mild spontaneous bleeding, or bleeding triggered by trauma, a surgery, or pregnancy/delivery
- Severe (<10% activity): Patients may have spontaneous (bleeding without trauma), severe, and even life-threatening bleeding
People sometimes develop a deficiency of factor VII related to other health conditions later in life. Liver disease may cause factor VII deficiency. It may also result from conditions in which absorption of vitamins, such as vitamin K, is reduced. Individuals who are taking the anticoagulant called warfarin can also develop a deficiency of factor VII.
What causes it?
Humans have 22 pairs of chromosomes (autosomes) plus the sex chromosomes (X and Y). Congenital factor VII deficiency is an “autosomal recessive” disorder that impacts both males and females. The “recessive” part means you need to inherit one abnormal gene from each of your parents to have the disease. Parents may either have congenital factor VII deficiency (2 abnormal genes) or be “carriers” (one normal and one abnormal gene). The illustrations below show the potential inheritance patterns of an autosomal recessive disorder.
These risks apply to each pregnancy, so if for example both parents are carriers, then each pregnancy has a 1 in 4 chance the child will be affected.
The factor VII gene is located on chromosome 13. Over 180 different mutations or abnormalities in the factor VII gene have been described in patients with congenital factor VII deficiency. The specific gene mutation does not always relate to the severity of bleeding symptoms.
Congenital factor VII deficiency has been reported to be associated with a number of other bleeding disorders including factor X (ten) deficiency, the gene for which is also on chromosome 13. More rarely, it is seen with factors V (five), VIII (eight), IX (nine), and XI (eleven) deficiencies.
What are the symptoms?
The most common symptoms of congenital factor VII deficiency include frequent and possibly severe nose bleeds, bleeding from the gums, very heavy or prolonged menstrual bleeding (in females), joint bleeds, bleeding into or around the brain, bleeding in the stomach or intestines (“GI”), and bleeding associated with circumcision (in males). In addition, patients with congenital factor VII deficiency often experience excessive bleeding after traumatic injury or a surgical or invasive procedure.
Even though congenital factor VII deficiency is rare, two large international studies have been done that asked about sites of bleeding. The International Registry on Congenital Factor VII Deficiency (IRF7) studied 515 patients. Data from 228 patients with different types of bleeding symptoms is shown below.
The European Network of Rare Bleeding Disorders (ENRBD) also looked at types of bleeding in many different bleeding disorders, including 224 patients with congenital factor VII deficiency. Just over half the patients with congenital factor VII deficiency registered had no symptoms, and less than 1 in 10 experienced severe bleeding.
People who have congenital factor VII deficiency should watch for these signs and symptoms in the parts of the body listed below. Contact your health care professional or treatment center team if you notice any of these symptoms:
Symptoms of bleeding in the brain
- Drowsiness or loss of consciousness
- Headache or muscle or neck ache
- Nausea and vomiting
- Sensitivity to light/scents/sounds (similar to migraine)
Symptoms of bleeding in the stomach or intestines
- Vomit that is black and syrupy or bright red
- Upset stomach
- Red- or black-colored stool
- Feeling of fullness/gas followed by bloody diarrhea
Symptoms of joint bleeding
- Swelling, pain, or warmth around a joint
- Inability to straighten or bend a joint normally
- Tight and shiny appearance of skin over the joint
Symptoms of muscle bleeding
- Tight and shiny appearance of skin
- Swelling in a limb around muscles
- Weakness, tingling, or pain in the arms or legs
- Pain and tenderness when using any muscle in the body
Symptoms of bleeding in and around the spinal cord
- Difficulty with urination or bowel movements
- Weakness, tingling, or pain in the arms or legs
Other symptoms to report
- Bleeding from the nose, gums, or mouth
- Bleeding after surgery
- Easy bruising
- Heavy menstrual bleeding in women
How is it diagnosed?
Two of the standard tests of clotting are the prothrombin time (PT) and activated partial thromboplasin time (aPTT). These both look at the time it takes for the liquid portion (plasma) in your blood to clot. As described above, factor VII works by binding to tissue factor at the site of the injured vessel wall. This part of clotting is best measured by the PT test, which will be prolonged (higher number of seconds – longer time to clot). Other tests used to diagnose congenital factor VII deficiency are thrombin time (TT) and factor VII activity levels.
|Prothrombin time (PT)||Prolonged|
|activated Partial Thromboplastin time (aPTT)||Normal|
|Factor VII activity level||Low|
There is another test related to the PT test called in international normalized ratio (INR), which is used to monitor warfarin therapy in patients who have clotting problems. It is not relevant to congenital factor VII deficiency.
How is it treated?
Treatment can depend on what type of bleed you may have or what type of procedure you may be undergoing. Your health care professional or treatment center team will make specific recommendations on the best approaches for each situation.
For minor injuries or nose/gum bleeds, your health care professional may suggest you use pressure or topical treatments that you can apply when you call their office or the treatment center for further instructions. For abnormal/excessive bleeding associated with monthly periods, use of hormonal treatment or other options may be recommended.
In situations where bleeding does not stop quickly, or when more serious bleeds or trauma occur, additional topical agents that stop bleeding (e.g. fibrin glue, nasal packing), oral agents (e.g. antifibrinolytic medications), and/or sources of plasma or recombinant factor VII replacement may be recommended to get your bleed under control.
In certain circumstances, patients with severe factor VII deficiency and frequent and/or severe bleeding (e.g. into the brain) may be treated with routine sources of plasma or recombinant factor VII replacement for a period of time after the bleeding episode. Your health care professional or treatment center team will make specific recommendations if and when this is appropriate.
Surgery and dental procedures
Surgical and dental procedures require pre-planning for patients with congenital factor VII deficiency. Your healthcare professional or treatment center team will partner with you to help decide on a strategy for helping to prevent bleeding during the procedure, and to decide on a post-operative course to make sure that you heal properly. A combination of topical treatments at the surgical site, medications, and/or sources of plasma or recombinant factor VII replacement therapy may be recommended. They will also coordinate with the dentist, surgeon, and anesthesiologist.
Patients with congenital factor VII deficiency should develop a plan with their healthcare professional or treatment center team to determine treatment needed around pregnancy, delivery, or in case of bleeding after birth.
People with inherited bleeding disorders should not take Aspirin®, nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen), and blood thinners, and should avoid certain herbal supplements (see resources page) which impact platelet function and thus can make bleeding symptoms worse. Contact your health care professional or treatment center team before starting any medications.
Complications of treatment
Antibodies and inhibitors
Sources of plasma or recombinant factor VII replacement therapy may be given in patients with congenital factor VII deficiency. Because your body does not have the normal factor VII, your body might not recognize the sources of plasma or recombinant factor VII replacement therapy. Your body may react and produce antibodies to factor VII replacement therapy. If the antibodies block the activity of factor VII, they are called inhibitors. Based on the STER study this is an extremely rare and poorly understood complication.
Tips for staying healthy
Develop a comprehensive care plan
Be sure to follow any maintenance or preventive measures your health care professional team has planned with you. Congenital factor VII deficiency can be a severe condition for some patients, but with the right care and support it can be properly managed. Even for those who are unsure of their severity, you need to develop a care plan based on your bleeding symptoms and history as well as any surgical or dental procedures that may need to be performed. This can be done with the experts at your HTC.
- Maintain good dental hygiene to avoid gum disease that could lead to bleeding.
- Maintain healthy blood iron levels through appropriate diet.
- Avoid anti-inflammatory drugs (e.g., aspirin, ibuprofen, naproxen) or herbal supplements that affect platelets, unless your health care professional directs you to use them.
- Discuss your desired activities and sports participation with your healthcare professional to determine which activities are most appropriate for you. At different ages, certain activities become more contact-intense and pose higher risk of bleeding.
- Women - Discuss your menstrual bleeding and any issues with planned pregnancy/childbirth with your hematologist and obstetrician/gynecology.
- Maintain or work at maintaining an optimum weight for your height and age.
Iron deficiency can occur frequently and even with small bleeds, and is a significant complication for patients with congenital factor VII deficiency with severe or frequent bleeding. If you are losing as little as 5 milliliters (about 1 teaspoon) of blood per day, you are also losing 2.5 milligrams of iron in your blood and you may become anemic. It is important that you manage your bleeds and tell your health care professional how frequently you are bleeding. Iron replacement therapy may be recommended.
Share your congenital FVII deficiency experience
Because it is rare, congenital factor VII deficiency often goes undiagnosed. And, unlike other rare bleeding disorders, there is not a lot of information available to help people with congenital factor VII deficiency understand their condition. Once you have a greater understanding and gain experience, you have an opportunity to become an advocate for yourself and others.
If you have family members, friends, or families with congenital factor VII deficiency in your community who have undiagnosed or untreated bleeding issues, is important that you share what you know with them as well as with your local HTC, hematologist, and bleeding disorders community. Doing so will help build a stronger congenital factor VII deficiency community.