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Factor VII deficiency
This rare condition affects the body's ability to form blood clots effectively, leading to prolonged or excessive bleeding. It is caused by genetic changes in the F7 gene and is usually identified in childhood or after a significant bleeding event.
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Overview
Factor VII deficiency is a rare, inherited bleeding disorder. Individuals with this condition have lower-than-normal levels of a protein called coagulation factor VII, or the factor VII they do have does not work correctly. This protein is essential for blood clotting, which is the process that stops bleeding after an injury [PMID:33678581]. Because of impaired clotting, affected individuals may experience prolonged or excessive bleeding.
This condition is one of the milder types of hereditary bleeding disorders compared to some other factor deficiencies, but its severity can vary greatly among individuals. It is also known as hereditary factor VII deficiency or congenital factor VII deficiency, reflecting its inherited nature. It is typically diagnosed in childhood, often after unexpected bleeding episodes or as part of investigations for a family history of bleeding.
Symptoms & clinical features
The symptoms of Factor VII deficiency can range from very mild to severe, even within the same family. In some individuals, the condition may only be discovered after surgery or an injury leads to excessive bleeding [PMID:33678581]. Common bleeding symptoms can include easy bruising, nosebleeds that are difficult to stop (epistaxis), and heavy or prolonged bleeding during menstruation (menorrhagia) in females.
More significant symptoms may include bleeding into joints (haemarthrosis), which can cause pain and long-term joint damage, or bleeding into muscles. Internal bleeding, particularly in the brain (intracranial haemorrhage) or digestive tract, is rare but can be life-threatening. Newborns may present with bleeding from the umbilical cord stump or intracranial bleeding shortly after birth.
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Affected organs
Factor VII deficiency primarily affects the blood and the vascular system, impacting the body's ability to maintain haemostasis (the process that stops bleeding). While bleeding can occur throughout the body, specific organs are more commonly affected by bleeding complications.
Frequent sites of bleeding include the skin (leading to bruising), mucous membranes (causing nosebleeds or gum bleeding), and the uterus (resulting in heavy menstrual periods). In severe cases, bleeding can occur in joints, leading to swelling and pain, and potentially long-term damage if not managed. Rarely, life-threatening bleeding can affect the brain or gastrointestinal tract.
Risks & severity
The severity of Factor VII deficiency is highly variable. Some individuals have no symptoms and are only diagnosed incidentally, while others experience recurrent and significant bleeding episodes. The level of factor VII activity in the blood generally correlates with the severity of symptoms; lower activity levels are typically associated with more severe bleeding. However, this is not always a perfect correlation, as other genetic and environmental factors can also influence the bleeding tendency [PMID:33678581].
The exact prevalence of Factor VII deficiency is not well established but is estimated to be between 1 in 300,000 and 1 in 500,000 people. While bleeding can occur at any age, symptoms often present during childhood. The lifetime risks associated with severe bleeding largely depend on the individual's factor VII levels and their exposure to situations that may provoke bleeding, such as surgery or trauma.
Genetic causes
Factor VII deficiency is caused by genetic changes (variants) in the F7 gene. This gene provides instructions for making coagulation factor VII, a vital protein in the blood clotting cascade. Factor VII plays a key role in initiating clotting by activating other clotting factors, leading to the formation of a stable blood clot that helps to stop bleeding [PMID:28770857].
Pathogenic variants in F7 can lead to either a reduced amount of factor VII protein in the blood or the production of factor VII that does not function correctly. Both scenarios result in impaired blood clotting, causing the characteristic bleeding symptoms of Factor VII deficiency. Hundreds of different variants in the F7 gene have been identified that can cause the condition.
- F7 coagulation factor VIIThe F7 gene provides instructions for producing coagulation factor VII, a vital protein that plays a central role in the blood clotting cascade, essential for stopping bleeding after injury.
Inheritance pattern
Factor VII deficiency has an autosomal recessive inheritance pattern. This means that an individual must inherit two altered copies of the F7 gene - one from each parent - to develop the condition. People who inherit only one altered copy of the F7 gene are called carriers. Carriers typically do not show symptoms of the condition themselves because their single working copy of the gene produces enough functional factor VII.
If two carriers have children, there is a 25% chance with each pregnancy that their child will inherit two altered F7 genes and therefore develop Factor VII deficiency. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two normal copies of the gene and not be a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Factor VII deficiency typically begins with observed bleeding symptoms, a family history of bleeding, or abnormal results from routine blood tests that screen for clotting problems. Initial screening tests may show a prolonged prothrombin time (PT), which specifically assesses the extrinsic pathway of coagulation, where factor VII plays an essential role. Other clotting tests, such as activated partial thromboplastin time (APTT), are usually normal in Factor VII deficiency.
To confirm the diagnosis, specific laboratory tests measure the activity of factor VII in the blood plasma [PMID:33678581]. A definitive diagnosis involves genetic testing, which looks for pathogenic variants in the F7 gene. Referral to a clinical genetics service via your GP or a specialist is part of the NHS Genomic Medicine Service pathway (R-code R115), where genetic counselling and testing can be arranged.
Management & lifestyle
Management of Factor VII deficiency focuses on preventing and treating bleeding episodes. For individuals with mild forms or infrequent bleeding, no regular treatment may be needed. However, it is crucial for affected individuals to avoid medications that can increase bleeding risk, such as aspirin or non-steroidal anti-inflammatory drugs (NSAIDs).
When bleeding occurs or before surgery, treatment primarily involves replacing the absent or deficient factor VII. This can be achieved through infusions of recombinant activated factor VII (rFVIIa) or fresh frozen plasma, which contains various clotting factors including factor VII. The specific treatment approach depends on the severity of the bleeding event, the individual's factor VII levels, and their general health. All management decisions are made by specialist haematology teams within the NHS, often in consultation with clinical geneticists.
UK care pathway
In the UK, individuals suspected of having an inherited bleeding disorder like Factor VII deficiency will typically be referred by their GP to a haematologist or a clinical genetics service. This usually falls under the NHS Genomic Medicine Service (GMS) pathways, with genetic testing available through specific R-codes, such as R115 for hereditary bleeding, platelet, and clotting disorders. Referral to a clinical geneticist will provide access to genetic counselling, which offers crucial information and support regarding the condition, its inheritance, and implications for family members and future planning. NHS specialist centres provide comprehensive care for bleeding disorders.
Frequently asked questions
What lifestyle changes might be recommended for someone with Factor VII deficiency?
Individuals with Factor VII deficiency should generally avoid medications that thin the blood, like aspirin. Contact sports or activities with a high risk of injury might need to be approached with caution or avoided, especially for those with more severe forms. Maintaining good dental hygiene is also important to prevent gum bleeding.
Will my children inherit Factor VII deficiency if I have it?
Because Factor VII deficiency is autosomal recessive, if you have the condition, you will pass one altered F7 gene copy to each of your children. Your children would only develop the condition if your partner is also a carrier or has the condition themselves. Genetic counselling can provide a more personalised risk assessment for your family.
What happens if I need surgery and have Factor VII deficiency?
If you have Factor VII deficiency and need surgery, your haematology team will work closely with your surgical team. They will likely give you infusions of factor VII replacement therapy before the procedure to ensure your blood can clot effectively and minimise the risk of excessive bleeding during and after surgery.
Is Factor VII deficiency the same as haemophilia?
Factor VII deficiency is a type of bleeding disorder, similar to haemophilia, but they are not the same. Haemophilia A and B involve deficiencies in Factor VIII and Factor IX, respectively, and typically follow an X-linked recessive inheritance pattern. Factor VII deficiency is an autosomal recessive condition affecting Factor VII.
Can women have Factor VII deficiency?
Yes, women can have Factor VII deficiency. Since it is an autosomal recessive condition, it affects males and females equally. Women with the condition may experience heavy menstrual bleeding (menorrhagia) or excessive bleeding during childbirth.
References
- Perry DJ. Factor VII deficiency. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2003. PMID: 14567537
- Perry DJ. Factor VII Deficiency. British journal of haematology. 2002. PMID: 12181036
- Napolitano M, Siragusa S, Mariani G. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy. Journal of clinical medicine. 2017. PMID: 28350321
- GRAHAM-STEWART CW. HEREDITARY FACTOR-VII DEFICIENCY. Lancet (London, England). 1964. PMID: 14219138
- Sevenet PO, Kaczor DA, Depasse F. Factor VII Deficiency: From Basics to Clinical Laboratory Diagnosis and Patient Management. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2017. PMID: 27701084
- Robinson KS. An overview of inherited factor VII deficiency. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2019. PMID: 31447397
- Qu C, Liu W, Chen L. Factor VII deficiency in China: Phenotype, genotype and current status of management. British journal of haematology. 2023. PMID: 36229963
- Ingerslev J, Kristensen HL. Clinical picture and treatment strategies in factor VII deficiency. Haemophilia : the official journal of the World Federation of Hemophilia. 1998. PMID: 9873815