Is Factor 7 Deficiency a Type of Haemophilia?
One of the most important distinctions to make is that factor VII (7) deficiency is not a type of haemophilia, but a separate and distinct rare bleeding disorder. The confusion arises because both conditions lead to problems with blood clotting. Classic haemophilia (types A and B) are X-linked, meaning they are far more common in males. In contrast, factor VII deficiency is inherited in an autosomal recessive pattern, meaning it affects males and females equally. While the symptoms of excessive bleeding can appear similar, the underlying genetic cause and the specific protein involved in the clotting process are different.
The Coagulation Cascade and Factor VII's Role
To understand the impact of factor VII deficiency, it is essential to grasp its role within the body’s coagulation cascade—the complex chain of reactions that leads to blood clot formation. This process is divided into three main pathways: the extrinsic, the intrinsic, and the common pathway.
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The Extrinsic Pathway: This is the shortest and most rapid route to clot formation, triggered by tissue damage. When an injury occurs, cells release tissue factor (TF). Factor VII, which circulates in the blood in an inactive form, binds to this tissue factor and becomes activated (FVIIa). The TF-FVIIa complex then activates factor X, initiating the common pathway. In factor VII deficiency, this initial trigger is compromised.
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The Intrinsic Pathway: This longer pathway is initiated by factors already present in the bloodstream, such as contact with a foreign surface. It involves factors XII, XI, IX, and VIII before converging with the common pathway at factor X.
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The Common Pathway: This is where the two pathways converge. It begins with the activation of factor X and culminates in the formation of a stable fibrin clot, involving factors V and II (prothrombin), and finally, factor I (fibrinogen). The body’s inability to properly initiate the extrinsic pathway due to missing or malfunctioning factor VII leads to slower and less efficient clot formation, resulting in prolonged or excessive bleeding.
Causes of Factor VII Deficiency
Factor VII deficiency can be either inherited (congenital) or acquired during a person's lifetime. The inherited form is the most common cause of this rare disorder.
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Congenital (Inherited): This form is caused by mutations in the F7 gene, which provides the instructions for making coagulation factor VII. As an autosomal recessive condition, a child must inherit a mutated F7 gene from both parents to be severely affected. Individuals with only one mutated copy are considered carriers and are usually asymptomatic.
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Acquired: While less common, factor VII deficiency can also develop from other health issues, including severe liver disease (since the liver produces clotting factors), vitamin K deficiency (vitamin K is necessary for the synthesis of FVII), or the use of certain medications, such as blood thinners like warfarin. In rare cases, it can be caused by the body producing an inhibitor or autoantibody against factor VII.
Symptoms and Clinical Severity
One of the most notable characteristics of factor VII deficiency is the wide variability in its clinical presentation. Some individuals with very low factor VII levels may show no bleeding symptoms, while others with higher levels may experience severe hemorrhages. Approximately one-third of affected individuals may remain asymptomatic throughout their lives.
Common symptoms include:
- Easy bruising
- Frequent nosebleeds (epistaxis)
- Bleeding gums
- Heavy or prolonged menstrual bleeding (menorrhagia) in women
- Prolonged or excessive bleeding after surgery, injury, or childbirth
Severe and life-threatening symptoms can include:
- Bleeding into joints (hemarthrosis)
- Bleeding into muscles
- Gastrointestinal (GI) bleeding
- Intracranial hemorrhage (bleeding in the brain), particularly in newborns or severely affected individuals
Diagnosis of Factor VII Deficiency
Diagnosis typically begins with a patient's personal and family bleeding history. Healthcare providers will order a series of blood tests to evaluate the function of the coagulation cascade. The key findings for factor VII deficiency are:
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Prolonged Prothrombin Time (PT): This test measures the function of the extrinsic and common pathways. Since factor VII initiates the extrinsic pathway, its deficiency will cause a prolonged PT.
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Normal Activated Partial Thromboplastin Time (aPTT): This test measures the intrinsic and common pathways. Because factor VII is not involved in the intrinsic pathway, the aPTT will typically be normal.
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Factor VII Assay: A specific assay to measure the activity level of factor VII in the blood is required to confirm the diagnosis and determine the severity of the deficiency. Genetic testing can also be performed to identify specific mutations in the F7 gene.
Management and Treatment
Management of factor VII deficiency depends on the severity of the bleeding and is overseen by a hematologist. Treatment options include:
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Recombinant Activated Factor VII (rFVIIa): This is a lab-produced version of activated factor VII, sold under the brand name NovoSeven. It is a preferred treatment option for treating bleeding episodes and is also used for prophylaxis (preventive treatment) in severe cases.
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Fresh Frozen Plasma (FFP): This blood product contains all clotting factors, including factor VII. It is an older treatment that carries a risk of fluid overload and is less specific than recombinant products.
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Prothrombin Complex Concentrates (PCC): These products contain a mix of vitamin K-dependent clotting factors, including factor VII. They are also derived from donated blood but are more concentrated than FFP.
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Antifibrinolytic Agents: Medications like tranexamic acid can help prevent clots from breaking down and may be used for mild bleeding episodes or in combination with replacement therapy.
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Vitamin K: For the acquired form of factor VII deficiency caused by vitamin K deficiency, supplementation is the appropriate treatment.
Comparison: Factor VII Deficiency vs. Hemophilia A
To clarify the key differences, here is a comparison between factor VII deficiency and the more well-known hemophilia A.
| Feature | Factor VII Deficiency | Hemophilia A |
|---|---|---|
| Cause | Mutation in the F7 gene. | Mutation in the F8 gene. |
| Inheritance | Autosomal Recessive | X-linked Recessive |
| Affected Population | Males and females equally. | Primarily males. |
| Coagulation Pathway | Affects the extrinsic pathway. | Affects the intrinsic pathway. |
| Lab Results | Prolonged PT; Normal aPTT. | Normal PT; Prolonged aPTT. |
| Treatment | rFVIIa (NovoSeven), PCC, FFP. | Recombinant FVIII, Emicizumab, etc. |
| Prevalence | Rare (1 in 300,000–500,000). | More common (1 in 10,000). |
Living with Factor VII Deficiency
Proper management is crucial for individuals with factor VII deficiency to lead healthy lives. This often involves working with a specialized hematologist and having a comprehensive plan in place, especially for surgical procedures or emergency situations. Precautions may include avoiding certain medications that increase bleeding risk, such as aspirin and NSAIDs. Genetic counseling is also recommended for families with a history of the disorder. With modern treatments, the prognosis for affected individuals is generally very good. For more resources and support, you can visit the National Bleeding Disorders Foundation.
Conclusion
In summary, while sharing characteristics of excessive bleeding, factor VII deficiency is a rare and distinct disorder from haemophilia. Its unique genetic inheritance, specific role in the coagulation cascade, and variable clinical severity require a precise diagnostic approach and tailored management strategy. With advancements in treatment options like recombinant factor VIIa, individuals can effectively manage their condition and minimize the risks of bleeding complications.
