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Factor Viii Deficiency

Disease Details

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Description: Factor VIII deficiency, also known as Hemophilia A, is a genetic disorder that impairs blood clotting, leading to prolonged bleeding.
Type: Factor VIII deficiency is a type of hemophilia, specifically Hemophilia A. The genetic transmission is X-linked recessive.
Signs And Symptoms: Haemophilia A’s phenotype has a quite wide range of symptoms encompassing both internal and external bleeding episodes. Individuals with more severe haemophilia tend to experience more intense and frequent bleeding, whereas those with mild haemophilia typically exhibit milder symptoms unless subjected to surgical procedures or significant trauma. Those with moderate haemophilia may display variable symptoms, falling within the spectrum between severe and mild forms.
One common early indicator of haemophilia is prolonged bleeding from venepuncture or heelpricks. These signs often prompt blood tests that confirm the presence of haemophilia. In individuals, especially those with moderate or mild haemophilia, any form of trauma can trigger the first significant bleed. Haemophilia substantially elevates the risk of protracted bleeding from ordinary injuries, and in severe cases, bleeding can occur spontaneously without an apparent cause. Bleeding episodes can manifest anywhere in the body. Superficial bleeding resulting from abrasions or shallow lacerations may persist, with scabs easily breaking due to the deficiency of fibrin, potentially leading to re-bleeding. While superficial bleeding poses challenges, more critical sites of bleeding include:
Joints
Muscles
Digestive tract
Brain
Prognosis: Two Dutch studies have followed haemophilia patients for a number of years. Both studies found that viral infections were common in haemophiliacs due to the frequent blood transfusions which put them at risk of acquiring blood borne infections, such as HIV, hepatitis B and hepatitis C. In the latest study which followed patients from 1992 to 2001, the male life expectancy was 59 years. If cases with known viral infections were excluded, the life expectancy was 72, close to that of the general population. 26% of the cases died from AIDS and 22% from hepatitis C. However, these statistics for prognosis are unreliable as there has been marked improvement of infection control and efficacy of anti-retroviral drugs since these studies were done.
Onset: Factor VIII deficiency, also known as Hemophilia A, typically presents with symptoms ranging from mild to severe, depending on the level of clotting factor present. In severe cases, it often becomes apparent in infancy or early childhood, usually before the age of two, through spontaneous bleeding or excessive bleeding after minor injuries. In milder cases, the onset may occur later, sometimes not becoming evident until adulthood, often after surgery or trauma.
Prevalence: Hemophilia A, which is caused by Factor VIII deficiency, affects approximately 1 in 5,000 male births worldwide.
Epidemiology: Haemophilia A occurs in approximately 1 in 5,000 males, while the incidence of haemophilia B is 1 in 30,000 in the male population, of these, 85% have haemophilia A and 15% have haemophilia B.
Intractability: Factor VIII deficiency, also known as Hemophilia A, is not considered intractable. While it is a chronic and lifelong condition, it can be managed effectively with treatments such as regular infusions of clotting factor concentrates, recombinant factor VIII, and other supportive therapies. Advances in medicine have significantly improved the quality of life for individuals with this condition.
Disease Severity: Factor VIII deficiency, also known as Hemophilia A, is a genetic disorder that leads to impaired blood clotting. The severity of the disease is classified based on the amount of functional Factor VIII in the blood:

1. **Severe Hemophilia A**: Less than 1% of normal Factor VIII activity. Individuals often experience spontaneous bleeding episodes, including into joints and muscles.

2. **Moderate Hemophilia A**: 1-5% of normal Factor VIII activity. Bleeding usually occurs after injuries but can sometimes happen spontaneously.

3. **Mild Hemophilia A**: 6-25% of normal Factor VIII activity. Bleeding typically occurs only after significant injuries or surgeries.

Maintaining Factor VIII levels through replacement therapy can help manage and reduce bleeding episodes.
Healthcare Professionals: Disease Ontology ID - DOID:12134
Pathophysiology: Factor VIII deficiency, also known as Hemophilia A, is a genetic disorder characterized by a deficiency or dysfunction of clotting factor VIII, a crucial protein in the blood coagulation process. The pathophysiology involves an inherited mutation in the F8 gene located on the X chromosome. This results in reduced or absent activity of factor VIII, impairing the formation of a stable blood clot. Consequently, individuals with this deficiency experience prolonged bleeding episodes, which can occur spontaneously or following injury or surgery. The severity of Hemophilia A can vary depending on the level of factor VIII activity in the blood.
Carrier Status: For factor VIII deficiency, commonly known as hemophilia A:

**Carrier Status:**
In hemophilia A, carrier status typically refers to females who have one defective copy of the factor VIII gene (located on the X chromosome) and one normal copy. They usually do not exhibit severe symptoms but can pass the condition to their offspring.

**Nan:**
The term "nan" does not apply directly in the context of factor VIII deficiency. Further context or explanation might be needed to provide relevant information related to "nan." If it refers to a specific abbreviation or terminology, please provide additional details.
Mechanism: Factor VIII deficiency, also known as Hemophilia A, is a genetic disorder that impairs the blood's ability to clot due to a deficiency in factor VIII, a crucial clotting protein.

**Mechanism:**
1. **Clot Formation Impairment:** In normal blood clotting, factor VIII is activated to factor VIIIa, which, in turn, acts as a cofactor for factor IXa in the conversion of factor X to factor Xa. This step is essential in forming the prothrombinase complex, leading to the conversion of prothrombin to thrombin and ultimately resulting in the formation of a fibrin clot. In individuals with factor VIII deficiency, this activation cascade is disrupted, leading to prolonged or uncontrolled bleeding.

**Molecular Mechanisms:**
1. **Genetic Mutations:** Hemophilia A is primarily caused by mutations in the F8 gene located on the X chromosome. These mutations can range from inversions, deletions, point mutations, to insertions, each having varying impacts on the expression or function of the factor VIII protein.
2. **Intron 22 Inversion:** One of the most common mutations is the intron 22 inversion, which disrupts the gene's transcription and translation, resulting in a lack of functional factor VIII.
3. **Missense Mutations:** These involve single nucleotide changes that can lead to an amino acid substitution in the factor VIII protein, potentially altering its function or stability.
4. **Nonsense Mutations:** These produce a premature stop codon, leading to truncated, non-functional factor VIII protein.
5. **Splice Site Mutations:** These can affect the proper splicing of precursor mRNA, resulting in defective mRNA and, consequently, an abnormal factor VIII protein.

In summary, the genetic mutations in the F8 gene lead to either a reduced level of factor VIII or a dysfunctional protein, severely impacting the coagulation cascade and manifesting as hemophilia A.
Treatment: In regards to the treatment of this genetic disorder, most individuals with severe haemophilia require regular supplementation with intravenous recombinant or plasma concentrate factor VIII. The preventative treatment regime is highly variable and individually determined. In children, an easily accessible intravenous port may have to be inserted to minimise frequent traumatic intravenous cannulation. These devices have made prophylaxis in haemophilia much easier for families because the problems of finding a vein for infusion several times a week are eliminated. However, there are risks involved with their use, the most worrisome being that of infection, studies differ but some show an infection rate that is high. These infections can usually be treated with intravenous antibiotics but sometimes the device must be removed, also, there are other studies that show a risk of clots forming at the tip of the catheter, rendering it useless. Some individuals with severe haemophilia, and most with moderate and mild haemophilia, treat only as needed without a regular prophylactic schedule. Mild haemophiliacs often manage their condition with desmopressin, a drug which releases stored factor VIII from blood vessel walls.
Compassionate Use Treatment: For Factor VIII deficiency, also known as Hemophilia A, compassionate use or off-label and experimental treatments may include:

1. **Gene Therapy:** Emerging gene therapies are being developed and tested to provide long-term solutions for Hemophilia A by introducing functional copies of the gene responsible for producing Factor VIII. One such treatment is valoctocogene roxaparvovec, which has shown promising results in clinical trials.

2. **Emicizumab (Hemlibra):** Although primarily approved for routine prophylaxis to reduce bleeding episodes in patients with Hemophilia A with or without Factor VIII inhibitors, it has also been used off-label in various dosing regimens tailored to individual patient needs.

3. **Fitusiran:** This is an experimental therapeutic agent that targets antithrombin. By reducing antithrombin levels, it aims to rebalance the coagulation system and reduce bleeding in Hemophilia A patients. It is currently undergoing clinical trials.

4. **Concizumab:** Another investigational treatment aimed at Hemophilia A and B with inhibitors. It is a monoclonal antibody designed to inhibit tissue factor pathway inhibitor (TFPI), thus improving clotting.

5. **Alternative Replacement Therapies:** Beyond standard recombinant and plasma-derived Factor VIII products, alternative replacement therapies, including modified Factor VIII products with extended half-lives, are being explored for better management and reduced infusion frequency.

These treatments, some still under clinical investigation, represent innovative approaches to enhancing the quality of life for patients with Hemophilia A. The availability and eligibility criteria for these treatments can vary based on regulatory approvals and clinical trial stipulations.
Lifestyle Recommendations: For Factor VIII deficiency, which is related to Hemophilia A, the following lifestyle recommendations are advised:

1. **Regular Exercise**: Engage in low-impact activities like swimming, walking, or cycling to strengthen muscles and joints without causing undue stress or injury.

2. **Protective Gear**: Use helmets, elbow pads, knee pads, and other protective gear during activities to prevent injuries.

3. **Good Dental Care**: Maintain excellent oral hygiene to prevent gum bleeding; regular visits to the dentist are important.

4. **Avoid Aspirin and NSAIDs**: These medications can increase bleeding risk; consult with a healthcare provider for safe alternatives.

5. **Healthy Diet**: Follow a balanced diet rich in nutrients to support overall health and maintain a healthy weight, reducing stress on the joints.

6. **Medical Identification**: Wear a medical alert bracelet or necklace identifying the condition in case of emergencies.

7. **Vaccinations**: Stay up-to-date with vaccinations to prevent infections that could complicate treatment.

8. **Education and Training**: Ensure that family members, caregivers, and school staff are educated about Hemophilia A and trained in emergency care procedures.

9. **Safe Environment**: Make home and work environments as safe as possible to minimize risk of injury.

10. **Regular Check-ups**: Maintain regular appointments with a hematologist for monitoring and management of the condition.

Exercise caution and moderation in activities to minimize bleeding risks and manage the condition effectively.
Medication: Factor VIII deficiency, also known as Hemophilia A, is primarily treated with replacement therapy, where the missing Factor VIII is replaced.

1. **Recombinant Factor VIII:** These are synthetically produced Factor VIII concentrates, such as Advate, Kogenate, and Recombinate.
2. **Plasma-Derived Factor VIII:** These are derived from donated human plasma, such as Hemofil M and Koate-DVI.
3. **Desmopressin (DDAVP):** This can be used in mild cases to stimulate the release of stored Factor VIII.
4. **Emicizumab (Hemlibra):** A newer monoclonal antibody that mimics the function of Factor VIII and is used for prophylaxis.

Consultation with a hematologist is crucial for appropriate treatment and management of Hemophilia A.
Repurposable Drugs: Currently, information on repurposable drugs specifically for Factor VIII deficiency (hemophilia A) is limited. The primary treatment involves replacement therapy with Factor VIII concentrates. However, other treatments are being explored that could potentially be applied to hemophilia A, such as drugs involved in gene therapy, agents that stabilize Factor VIII, or those that improve the body's own clotting mechanisms.

For more precise suggestions on repurposable drugs, research into pathways and existing drugs used in related conditions like other bleeding disorders might provide insights. Always consult recent research articles or a healthcare professional for the most current information.
Metabolites: Metabolites typically measured or monitored in relation to Factor VIII deficiency (Hemophilia A) primarily include Factor VIII activity levels and von Willebrand factor (vWF) levels. These measurements help assess the severity of the deficiency and guide treatment.
Nutraceuticals: There are no specific nutraceuticals that have been proven effective for the treatment of Factor VIII deficiency, also known as hemophilia A. The primary treatment involves replacement therapy with Factor VIII concentrates to manage and prevent bleeding episodes. It is important for individuals with hemophilia A to consult healthcare providers for appropriate management and treatment options.
Peptides: Factor VIII deficiency, also known as Hemophilia A, is a genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. It is caused by a mutation in the F8 gene, leading to deficient or defective coagulation factor VIII.

Peptides: Research is being conducted on peptide-based therapies to enhance the stability and activity of factor VIII or to promote haemostasis through alternative pathways. These peptides may offer new treatment avenues with potentially fewer complications than traditional factor replacement therapies.

Nan: Nanotechnology is being explored to improve the delivery and efficacy of factor VIII products. Nanoparticles can be used to encapsulate factor VIII to protect it from degradation and prolong its presence in the circulation, potentially reducing the frequency of infusions required for patients.

Advancements in both peptide and nanotechnology research hold promise for improving the management of Factor VIII deficiency.