Background

Hemophilia B, or Christmas disease, is a rare and inherited bleeding disorder. It is caused by a clotting factor IX (FIX) deficiency, which is essential for the blood to clot appropriately and prevent excessive bleeding. Hemophilia B is one of two types of hemophilia, with hemophilia A being more common, caused by a deficiency of clotting factor VIII (FVIII). The genetic basis of hemophilia B lies on the X chromosome, making it an X-linked recessive disorder.

This means the defective gene responsible for hemophilia B is on the X chromosome. The XY and XX chromosomes are found in males, whereas the XX chromosome is found in females. Suppose a male inherits the faulty gene on his X chromosome. In that case, he will develop hemophilia B because he lacks a second X chromosome with a functioning factor IX gene to compensate.

In contrast, females usually carry the defective gene, as they have another healthy X chromosome to balance the affected one. However, in rare cases, females can develop symptoms if they inherit the defective gene on both X chromosomes or if their clotting factor levels are severely reduced. Symptoms of hemophilia B vary in severity and can range from mild to severe, depending on the level of factor IX in the blood.

Individuals with mild hemophilia B may only experience bleeding problems after surgery or injury, while those with severe hemophilia B can have spontaneous bleeding episodes into joints and muscles. Common signs of hemophilia B include prolonged bleeding after cuts or injuries, frequent nosebleeds, large bruises, and bleeding into joints, leading to joint pain and damage. 

Epidemiology

Hemophilia is a group of rare bleeding disorders caused by deficiencies in specific clotting factors. The three main types are: 

• Hemophilia A: Prevalence is approximately 1 in 5,000 live males, making up about 85% of all hemophilia cases. 
• Hemophilia B: Prevalence is approximately 1 in 40,000 live males, accounting for about 15% of all hemophilia cases. 
• Hemophilia C: Prevalence is approximately 1 in 100,000 live births, representing about 1% of all hemophilia cases. 

While Hemophilia B is less common than Hemophilia A, both are rare disorders. Hemophilia C is even rarer in comparison. The prevalence of hemophilia is generally equal among all ethnic groups, but consanguinity (marriage between close relatives) can increase the frequency of specific types within certain communities. 

For example, the Egyptian population has a higher prevalence of Hemophilia A due to frequent consanguineous marriages. Similarly, Ashkenazi Jews have a relatively higher prevalence of Hemophilia A and other genetic disorders because of a founder effect and historical patterns of consanguinity within the community. 

Anatomy

Pathophysiology

Normal Blood Coagulation Process: 

• When a blood vessel is injured, the body initiates a series of complex reactions known as the coagulation cascade to form a stable blood clot at the injury site. 
• The coagulation cascade involves a series of clotting factors, including factor IX, that interact stepwise to produce fibrin, a protein that strengthens the platelet plug and stabilizes the blood clot. 

Factor IX Deficiency: 

• Hemophilia B is caused by a genetic mutation leading to a deficiency or dysfunction of clotting factor IX, a crucial component of the coagulation cascade. 
• Factor IX deficiency results in an impaired ability to convert inactive factor X (FX) to its active form, FXa, thus disrupting the final common pathway of blood coagulation. 

Impaired Clot Formation: 

• Due to the deficiency of factor IX, the coagulation cascade cannot proceed normally, leading to a delay or failure in forming a stable fibrin clot at the site of blood vessel injury. 
• Without a properly formed clot, bleeding is prolonged, and individuals with Hemophilia B are at risk of experiencing spontaneous bleeding into joints, muscles, and other tissues. 

Inheritance: 

• Hemophilia B is an X-linked recessive disorder, meaning the gene responsible for producing factor IX is on the X chromosome. 
• Males have one X chromosome and one Y chromosome, so if they inherit a defective X chromosome from their mother, they will have Hemophilia B. 
• Females have two X chromosomes and can be carriers of the Hemophilia B gene. They typically do not experience bleeding symptoms but can pass the condition to their children. 

Etiology

Hemophilia B is an X-linked recessive genetic disorder caused by a mutation in the F9 gene located on the X chromosome. The F9 gene produces the clotting factor IX (FIX), essential for normal blood coagulation. Mutations in this gene lead to a deficiency or dysfunction of factor IX, resulting in the characteristic bleeding disorder observed in Hemophilia B. 

The etiology of Hemophilia B include: 

• X-Linked Recessive Inheritance: The F9 gene is located on the X chromosome. Males have one X chromosome and one Y chromosome, while females have two X chromosomes. Since Hemophilia B is an X-linked recessive disorder, it primarily affects males. Suppose a male inherits the defective X chromosome carrying the mutated F9 gene from his carrier mother. In that case, he will have Hemophilia B because he lacks another X chromosome to compensate for the defective one. 
• Carrier Females: Carrier females have one normal X chromosome, and one affected X chromosome with the mutated F9 gene. While they do not experience bleeding symptoms, they can pass the mutated gene to their children. Carrier females have a 50% chance of passing the defective X chromosome to their sons, leading to Hemophilia B. 
• Spontaneous Mutations: In some cases, Hemophilia B can also occur due to spontaneous mutations in the F9 gene. These cases may not have a family history of the disorder. 

Genetic testing and family history evaluation are crucial for diagnosing Hemophilia B and determining its inheritance pattern. Identifying carriers and affected individuals within families can help with genetic counseling and family planning decisions. 

Genetics

Prognostic Factors

• Severity of Hemophilia: The severity of Hemophilia B is based on the residual activity of factor IX in the blood. It is classified into mild, moderate, and severe forms, with severe hemophilia having less than 1% of normal factor IX activity, moderate hemophilia having 1% to 5% activity, and mild hemophilia having 5% to 40% activity. Generally, individuals with severe Hemophilia B are more prone to frequent and severe bleeding episodes, while those with mild or moderate Hemophilia B may experience milder bleeding symptoms. 
• Age of Diagnosis: Early diagnosis and prompt initiation of appropriate treatment can significantly improve the prognosis for individuals with Hemophilia B. Early management can help prevent joint damage and reduce the impact of bleeding episodes on overall health and quality of life. 
• Joint Health: Repeated bleeding into joints, a condition called hemophilic arthropathy, is a common complication of Hemophilia B. The frequency and severity of joint bleeding can significantly impact long-term joint health and function. Early and effective treatment can help prevent or minimize joint damage. 
• Inhibitors: In some cases, individuals with Hemophilia B may develop inhibitors, which are antibodies that neutralize the clotting factor replacement therapy, making it less effective. The development of inhibitors can complicate treatment and increase the risk of bleeding complications. 
• Treatment Adherence: Adherence to treatment regimens, including regular factor IX replacement therapy or other prophylactic treatments, is crucial for managing Hemophilia B effectively. Consistent adherence can help prevent bleeding episodes and long-term complications. 
• Access to Care: Access to specialized hemophilia treatment centers and comprehensive care can significantly impact the prognosis of Hemophilia B. Regular care and access to experienced healthcare professionals can improve patient outcomes. 
• Lifestyle and Physical Activity: A healthy lifestyle and appropriate physical activities can help maintain joint health and overall well-being in individuals with Hemophilia B. 
• Genetic Factors: The specific genetic mutation causing Hemophilia B can also influence disease severity and clinical outcomes. 

Clinical History

The primary clinical features of Hemophilia B include: 

• Bleeding Episodes: The hallmark of Hemophilia B is bleeding episodes, which can occur in various locations in the body. Common sites of bleeding include joints, muscles, and soft tissues. The frequency and severity of bleeding episodes depend on the severity of Hemophilia B. 
• Joint Bleeding (Hemarthrosis): Hemophilia B can lead to repeated bleeding into joints (hemarthrosis), especially in weight-bearing joints like the knees, ankles, and elbows. This can cause joint pain, swelling, and reduced range of motion. 
• Soft Tissue Bleeding: Hemophilia B can also cause bleeding into muscles and soft tissues, leading to deep bruising and pain. 
• Prolonged Bleeding after Injury or Surgery: Individuals with Hemophilia B may experience prolonged bleeding after minor injuries, cuts, or dental procedures. 
• Easy Bruising: Hemophilia B can result in easy bruising due to impaired blood clotting. 

Age Group and Clinical Presentation: 

• Infants and Toddlers: Hemophilia B may become apparent in infancy or early childhood when the child starts crawling or walking, and experiences repeated joint bleeding episodes.  
• Children and Adolescents: Joint bleeding continues to be a significant concern during this age group, especially with increased physical activity and participation in sports.  
• Adults: Hemophilia B can continue to cause bleeding episodes and joint complications in adults. It may also impact their ability to perform certain physical activities or engage in labor-intensive occupations. 

Physical Examination

The key aspects of the physical examination for Hemophilia B: 

General Observation: 

• Observe the overall appearance and general health status of the individual. 
• Look for any signs of pallor, fatigue, or weakness indicating ongoing bleeding or anemia. 

Joint Assessment: 

• Carefully examine and palpate the joints, especially weight-bearing joints like knees, ankles, and elbows. 
• Check for signs of joint swelling, warmth, and tenderness, which may indicate hemarthrosis (bleeding into the joints). 

Musculoskeletal Assessment: 

• Evaluate the range of motion of joints and assess for any limitations or discomfort during movement. 
• Assess muscle strength and function, as repeated bleeding can lead to weakness and decreased muscle tone. 

Skin Examination: 

• Look for signs of easy bruising, petechiae (small pinpoint red spots on the skin), and ecchymosis (larger patches of bruising). 
• Examine the skin for any areas of soft tissue swelling or hematoma formation. 

Bleeding Sites: 

• Inspect any wounds or sites of recent injuries to assess the degree and duration of bleeding. 
• Check for signs of active bleeding or bleeding that have not stopped or have reoccurred. 

Neurological Assessment: 

• Evaluate neurological function, especially if there is concern about potential bleeding in the head or brain. 
• Look for symptoms such as headaches, altered mental status, seizures, or focal neurological deficits. 

Vital Signs: 

• Measure blood pressure, heart rate, respiratory rate, and temperature to assess the hemodynamic status. 

Laboratory Investigations: 

• In addition to the physical examination, laboratory tests are crucial for confirming the diagnosis and assessing the severity of Hemophilia B. These may include: 
• Coagulation studies include activated partial thromboplastin time (aPTT) and clotting factor assays to measure factor IX levels. 
• Complete blood count (CBC): to assess for anemia or platelet abnormalities. 

Age group

Associated comorbidity

Hemophilia B does not typically cause specific comorbidities; however, individuals with the condition may be at risk of complications due to bleeding episodes. Joint damage (hemophilic arthropathy) and chronic pain are potential long-term consequences, especially if bleeding episodes are not adequately managed. Individuals with Hemophilia B may also experience psychosocial challenges related to their condition. 

Associated activity

Acuity of presentation

The acuity of presentation in Hemophilia B can vary depending on the severity of the condition and the timing of the bleeding episode. Acute bleeding episodes, such as joint bleeds or significant trauma-related bleeding, require immediate medical attention and treatment to control the bleeding and prevent further complications. 

Differential Diagnoses

• Hemophilia A: Hemophilia A is the most common form of hemophilia, caused by a deficiency of clotting factor VIII. The symptoms and presentation of hemophilia A are similar to those of hemophilia B, so distinguishing between the two is critical. 
• Von Willebrand disease (VWD): This is the most prevalent hereditary bleeding condition, and it is caused by a lack or malfunction of von Willebrand factor (VWF). VWD can cause bleeding symptoms, such as nosebleeds, easy bruising, and heavy menstrual periods. 
• Liver disease: Liver illness can impair the production of clotting factors such as factor IX. In some cases, liver disease can cause bleeding tendencies like hemophilia B. 
• Acquired factor IX deficiency: Rarely, some medical conditions or medications can lead to an acquired deficiency of factor IX, causing symptoms resembling hemophilia B. 
• Platelet disorders: Conditions that affect platelet function or count, such as idiopathic thrombocytopenic purpura (ITP) or platelet function disorders, can present with bleeding symptoms. 
• Vitamin K deficiency: Vitamin K is required for the creation of clotting factors such as factor IX. A deficiency in vitamin K can lead to bleeding problems. 
• Coagulation factor inhibitors: In some cases, patients may develop antibodies (inhibitors) against clotting factors, including factor IX, leading to bleeding issues. 
• Disseminated intravascular coagulation (DIC): DIC is a complex disorder that can cause both bleeding and clotting, depending on its stage and severity. 
• Hemorrhagic disorders: There are various other inherited or acquired hemorrhagic disorders that can lead to abnormal bleeding. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The treatment approach depends on the severity of Hemophilia B, the frequency and type of bleeding episodes, and individual patient factors. The main components of the treatment paradigm for Hemophilia B include: 

Clotting Factor Replacement Therapy: 

• The primary treatment for Hemophilia B involves replacing the deficient or dysfunctional factor IX with exogenous factor IX concentrates. These concentrates can be derived from human plasma or produced through recombinant technology. 
• Clotting factor replacement therapy can be administered on-demand (treating bleeding episodes as they occur) or prophylactic therapy (regularly scheduled infusions to prevent bleeding). 
• Prophylactic therapy is recommended for individuals with severe Hemophilia B to prevent joint damage and reduce the frequency of spontaneous bleeding. 

Personalized Treatment Plans: 

• Treatment plans for Hemophilia B should be individualized based on the patient’s specific needs, lifestyle, and preferences. 
• Factors such as the frequency of bleeding episodes, joint health, and patient compliance are considered in tailoring the treatment approach. 

Hemostatic Agents: 

• For minor bleeding episodes or as an adjunct to factor replacement therapy, topical hemostatic agents such as fibrin sealants or hemostatic dressings can be used. 

Gene Therapy: 

• Gene therapy is an emerging treatment approach for Hemophilia B that involves introducing a functional copy of the F9 gene into the patient’s cells to produce factor IX. 
• Gene therapy has shown promising results in clinical trials and may offer a more long-term treatment option for some individuals with Hemophilia B. 

Inhibitor Management: 

• Some individuals with Hemophilia B may develop inhibitors (neutralizing antibodies) against factor IX replacement therapy, reducing effectiveness. 
• Inhibitor management may involve alternative clotting factor concentrates, immune tolerance induction (ITI) therapy, or other treatment modalities. 

Physical Therapy: 

• Physical therapy is essential for maintaining joint health and preventing deformities in Hemophilia B individuals. 
• Range of motion exercises and muscle-strengthening activities can help improve joint function and reduce the risk of joint bleeding. 

Comprehensive Hemophilia Care: 

• Comprehensive care at specialized hemophilia treatment centers is recommended to provide optimal management of Hemophilia B. 

Education and Support: 

• Patient education and support are crucial for self-management and adherence to treatment plans. 

• Education should cover aspects such as recognizing bleeding symptoms, administering factor replacement therapy, and injury prevention. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-a-non-pharmacological-approach-for-treating-hemophilia-b

Non-pharmacological approaches can be used with pharmacological treatments to manage hemophilia B. It’s important to note that non-pharmacological approaches alone may not control bleeding in severe cases. Some non-pharmacological approaches for treating hemophilia B include: 

• Physical Therapy: Physical therapy can help improve joint strength, flexibility, and stability, reducing the risk of bleeding in target joints. A physical therapist can create personalized exercise programs to enhance joint health and function while minimizing the risk of injury. 
• RICE (Rest, Ice, Compression, Elevation): RICE is a standard approach for managing acute joint bleeds in hemophilia B patients. Rest the affected joint, apply ice to reduce swelling, apply compression using bandages, and elevate the limb to reduce blood flow to the area. 
• Joint Protection: Avoiding high-impact activities, maintaining a healthy weight, and using supportive devices (e.g., braces) can help protect joints. 
• Prophylactic Measures: Regular prophylaxis with factor IX concentrate is the primary pharmacological approach to prevent bleeding in hemophilia B patients. 
• Bleeding Prevention Education: Hemophilia B patients, their families, and caregivers should receive comprehensive education on bleeding prevention.  
• Genetic Counseling: Genetic counseling can provide information about the inheritance pattern of hemophilia B, family planning options, and potential risks for future generations.  
• Psychological Support: Living with a chronic condition like hemophilia B can be challenging emotionally and psychologically.

Role of Factor IX concentrate in the Treatment of Hemophilia B

Factor IX concentrate is a crucial component of the treatment for hemophilia B. The main goal of treatment is to replace the missing or deficient factor IX, thereby restoring the blood’s ability to clot and preventing bleeding episodes. Factor IX concentrate is the primary pharmaceutical agent used for this purpose. 

Factor IX concentrate is available in two primary forms: 

• Recombinant Factor IX: Recombinant factor IX is produced using genetic engineering techniques, where the factor IX gene is inserted into host cells, and the cells are cultured to produce factor IX. It is virtually identical to the naturally occurring factor IX in the body. Recombinant factor IX is considered safe and effective in providing clotting factor replacement for hemophilia B patients. 
• Plasma-Derived Factor IX: Plasma-derived factor IX is obtained from human blood plasma collected from carefully screened donors. The plasma is purified to extract factor IX concentrate, which contains the clotting factor required for hemostasis in hemophilia B patients. Plasma-derived factor IX has been used for decades and has a long history of safety and efficacy. 

Both forms of factor IX concentrate are administered intravenously (IV) by infusion. The dose and frequency of administration depend on the individual’s specific needs, the severity of the disease, and the presence of bleeding or prophylactic treatment requirements. 

Factor IX concentrate is used in two main treatment strategies for hemophilia B: 

• Prophylaxis: Prophylactic treatment involves regular and scheduled infusions of factor IX concentrate to prevent bleeding episodes. This approach is commonly recommended for patients with severe hemophilia B to reduce the risk of joint and other bleeding complications. 
• On-Demand Treatment: On-demand treatment involves administering factor IX concentrate when a bleeding episode occurs. The goal is to control and stop the bleeding promptly. 

BeneFIX: BeneFIX is available as an extended half-life (EHL) product, known as BeneFIX Rixubis. The EHL formulation allows for less frequent dosing while maintaining adequate factor IX levels. EHL products are designed to improve convenience and potentially enhance treatment adherence. 

BeneFIX is administered intravenously (IV) through a needle or catheter directly into the bloodstream. The dosing and frequency of administration depend on the individual’s specific treatment plan, disease severity, and bleeding history. 

Role of Bypassing products (rFVIIa products or FEIBA) in treating Hemophilia B

Bypassing products, such as recombinant activated factor VIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC) like FEIBA (Factor Eight Inhibitor Bypassing Activity), play a critical role in the treatment of hemophilia B with inhibitors.

Inhibitors are antibodies some hemophilia B patients developed against factor IX, rendering traditional factor IX replacement therapy less effective.

Bypassing agents are an alternative treatment strategy to achieve hemostasis in these inhibitor patients. The role of bypassing products in treating hemophilia B with inhibitors: 

Recombinant Activated Factor VIIa (rFVIIa) Products: 

• rFVIIa acts directly on the surface of activated platelets to initiate the coagulation process, forming fibrin clots independently of factor IX in the traditional clotting cascade. 
• rFVIIa is primarily used in patients with inhibitors to factor VIII and, in some cases, inhibitors to factor IX. It promotes clot formation at the bleeding site, bypassing the need for factors VIII and IX. 

Activated Prothrombin Complex Concentrates (aPCC) – FEIBA: 

• FEIBA is a complex mixture of clotting factors, including activated factors II, VII, IX, and X and non-activated factors. It provides multiple factors involved in the clotting process, effectively supporting hemostasis even in the presence of inhibitors. 
• Use in Inhibitor Patients: FEIBA is an important option for treating bleeding episodes in hemophilia B patients with inhibitors. It helps control bleeding and promotes clot formation despite the presence of inhibitors. 

Role of Gene therapy in managing Hemophilia B

Gene therapy is an innovative and promising treatment approach for hemophilia B. It involves introducing a functional factor IX gene into the patient’s cells to produce factor IX continuously, thus addressing the condition’s underlying cause.

Hemophilia B is caused by a deficiency or dysfunction of clotting factor IX, and gene therapy aims to provide a long-term solution by restoring the missing or defective factor. 

Gene therapy offers several potential benefits for hemophilia B treatment: 

• Long-term Treatment: Gene therapy has the potential to provide long-lasting or even permanent factor IX production, reducing the need for regular factor replacement infusions. 

• Reduction in Bleeding Episodes: Continuous factor IX production can decrease the frequency and severity of bleeding episodes, improving the patient’s quality of life. 
• Reduced Joint Damage: By maintaining higher factor IX levels, gene therapy may help prevent or reduce joint damage associated with recurrent bleeds. 
• Improved Prophylaxis: Gene therapy may offer an alternative to traditional prophylactic factor infusions, simplifying treatment and enhancing patient compliance. 
• Personalized Approach: Gene therapy can be tailored to individual patients, considering age, disease severity, and overall health. 

use-of-intervention-with-a-procedure-in-treating-hemophilia-b

The interventions with procedures used in treating hemophilia B include: 

• Joint Aspiration and Injection: In significant joint bleeding (hemarthrosis), joint aspiration may be performed to remove excess blood and reduce pressure within the joint. Joint injections of corticosteroids or other medications may be considered to reduce inflammation and alleviate pain. 
• Hemostatic Agents: Hemostatic agents are topical substances promoting clotting and controlling bleeding in external or surface wounds. They are applied directly to the bleeding site and can be helpful in minor cuts or wounds. 
• Central Venous Access Devices (CVADs): For patients requiring frequent factor replacement infusions, the placement of a central venous access device, such as a port or central line, may be considered. CVADs provide easier and more reliable access for factor infusions and reduce the need for multiple needle sticks. 
• Embolization: In severe internal bleeding, such as gastrointestinal or urological bleeds, embolization may be performed. During embolization, a catheter is inserted into the affected blood vessel, and embolic agents block or occlude the bleeding vessel, stopping the bleeding. 
• Splenectomy: For some patients with severe hemophilia B and recurrent bleeding episodes, the removal of the spleen (splenectomy) may be considered. The spleen can be a source of bleeding, and removing it can reduce bleeding episodes. 
• Orthopedic Procedures: Orthopedic procedures may be required to address complications related to recurrent joint bleeds, such as chronic synovitis or joint damage. These procedures aim to improve joint function and reduce pain. 
• Surgical Interventions: In certain situations, surgical interventions may be necessary to manage complications of hemophilia B, such as bleeding after major surgery or trauma. Hemostasis is carefully managed during and after surgery by administering factor IX concentrate and other hemostatic agents. 

use-of-phases-in-managing-hemophilia-b

The critical phases in managing hemophilia B include: 

• Acute Bleed Management: This phase focuses on the immediate management of bleeding episodes, such as joint bleeds, muscle bleeds, or other types of bleeding. The primary goal is to stop the bleeding and achieve hemostasis promptly. Treatment involves administering factor IX concentrate to raise factor IX levels and control the bleeding. Hemostatic agents and other supportive measures may also be used to control bleeding. 

• Prophylaxis is a preventive treatment phase involving regular and scheduled infusions of factor IX concentrate to prevent bleeding episodes. It is often recommended for patients with severe hemophilia B to reduce the risk of joint and other bleeding complications. Prophylactic treatment aims to maintain factor IX levels above a certain threshold to prevent spontaneous bleeds. 
• On-Demand Treatment: On-demand treatment refers to administering factor IX concentrate when a bleeding episode occurs. This phase is particularly important for individuals who are not on prevention or experience breakthrough bleeding despite prophylaxis. The goal is to control and stop the bleeding promptly. 
• Perioperative Management: Perioperative management focuses on managing bleeding risk during and after surgical procedures. It involves planning and coordinating factor IX replacement therapy to ensure adequate hemostasis during surgery and post-operative recovery. Collaboration between the hematologist, surgeon, and anesthesiologist is crucial to optimize perioperative care. 
• Joint Health and Rehabilitation: This phase involves promoting joint health and preventing complications from recurrent joint bleeds. Physical therapy, joint protection techniques, and exercises to improve joint strength and flexibility are commonly used. The goal is maintaining joint function and reducing the risk of chronic joint damage (hemophilic arthropathy). 
• Management of Inhibitors: Some hemophilia B patients may develop inhibitors (neutralizing antibodies) against factor IX, rendering traditional factor replacement less effective. This phase focuses on using bypassing agents, such as recombinant activated factor VIIa (rFVIIa) or activated prothrombin complex concentrates (aPCC), as alternative treatments for patients with inhibitors. 
• Gene Therapy (Emerging Phase): Gene therapy is an emerging treatment approach for hemophilia B that involves introducing a functional factor IX gene into the patient’s cells to produce factor IX continuously. This phase explores the potential for long-term factor IX production, reducing the need for regular infusions. 

Medication

Future Trends

Media Gallary

References

Hemophilia B.ncbi.nlm.nih 

Modern haemophilia care.pubmed.ncbi.nlm.nih 

The hemophilias.pubmed.ncbi.nlm.nih 

The past and future.pubmed.ncbi.nlm.nih