Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

What Is Hemophilia? In Which If Bleeding Starts Then It Does Not Stop!

Hemophilia is a rare genetic disorder characterized by the inability of blood to clot normally, leading to prolonged bleeding. It is a lifelong condition that requires careful management and treatment to prevent complications.

The Anatomy of Hemophilia

Hemophilia is primarily caused by a deficiency in clotting factors, specifically Factor VIII (hemophilia A) or Factor IX (hemophilia B). These clotting factors are essential for the blood to form clots and stop bleeding when blood vessels are injured. Without adequate levels of these clotting factors, individuals with hemophilia experience difficulty in forming clots, resulting in prolonged bleeding episodes.

The Inheritance Factor: Genetics of Hemophilia Hemophilia is typically inherited in an X-linked recessive pattern, meaning that the gene mutation responsible for the disorder is located on the X chromosome. Since males have only one X chromosome (XY), they are more likely to inherit hemophilia if their mother carries the gene mutation. Females, on the other hand, have two X chromosomes (XX), so they are usually carriers of the gene mutation and may pass it on to their children. Types of Hemophilia There are two main types of hemophilia: hemophilia A and hemophilia B. Hemophilia A is caused by a deficiency of Factor VIII, while hemophilia B is caused by a deficiency of Factor IX. The severity of hemophilia can vary depending on the level of clotting factor present in the blood. Individuals with severe hemophilia have very low levels of clotting factor and are more prone to spontaneous bleeding, while those with mild or moderate hemophilia may only experience bleeding after injury or surgery. Symptoms of Hemophilia Common symptoms of hemophilia include excessive bleeding from minor injuries, prolonged bleeding after surgeries, and spontaneous internal bleeding. External symptoms may include large bruises (hematomas), joint pain and swelling due to bleeding into the joints (hemarthrosis), and prolonged nosebleeds. Internal bleeding can occur in the muscles, joints, and other organs, leading to serious complications if not promptly treated. Severity Levels of Hemophilia Hemophilia can be classified into three severity levels: mild, moderate, and severe. The severity is determined by the amount of clotting factor present in the blood. Individuals with severe hemophilia have less than 1% of the normal clotting factor levels and are at the highest risk of spontaneous bleeding. Those with moderate hemophilia have 1% to 5% of normal clotting factor levels, while those with mild hemophilia have 5% to 40% of normal clotting factor levels. Diagnosis and Screening Diagnosing hemophilia often involves blood tests to measure clotting factor levels and assess the blood's ability to clot. Genetic testing may also be performed to identify the specific gene mutation responsible for hemophilia. Screening for hemophilia is recommended for individuals with a family history of the disorder or those who exhibit symptoms such as prolonged bleeding or easy bruising. Treatment Options Treatment for hemophilia aims to prevent bleeding episodes and manage symptoms. The primary treatment involves replacing the missing clotting factor through regular infusions of clotting factor concentrates. These infusions can be administered on a prophylactic basis to prevent bleeding or on-demand to treat bleeding episodes as they occur. Prophylactic Treatment Prophylactic treatment involves regular infusions of clotting factor concentrates to maintain adequate levels of clotting factor in the blood and prevent bleeding episodes. This approach is particularly beneficial for individuals with severe hemophilia who are at a higher risk of spontaneous bleeding. Prophylactic treatment can help reduce the frequency and severity of bleeding episodes, as well as minimize long-term complications such as joint damage. On-Demand Treatment On-demand treatment is administered to control bleeding episodes when they occur. This typically involves infusions of clotting factor concentrates at the first sign of bleeding or injury. On-demand treatment is essential for managing acute bleeding episodes and preventing complications such as excessive blood loss and damage to organs and tissues. Complications and Challenges Complications of hemophilia may arise from prolonged bleeding episodes and inadequate treatment. Chronic joint damage is a common complication, particularly in individuals with frequent joint bleeds. Muscle bleeds can also occur, leading to pain, swelling, and reduced mobility. In severe cases, life-threatening bleeding episodes may occur, particularly in the brain or other vital organs. Living with Hemophilia Living with hemophilia requires ongoing management and support to maintain overall health and well-being. This includes regular medical care, adherence to treatment plans, and monitoring for potential complications. Physical therapy and exercise are also important for preserving joint function and mobility, as well as reducing the risk of bleeds. Support Networks Support networks and advocacy groups play a crucial role in providing resources and support for individuals and families affected by hemophilia. These organizations offer educational materials, financial assistance programs, and opportunities for social interaction and peer support. By connecting with others facing similar challenges, individuals with hemophilia can find encouragement, advice, and solidarity in their journey. Advancements in Treatment Recent advancements in treatment offer promising prospects for improving the management of hemophilia and potentially finding a cure. Gene therapy, in particular, holds great potential for correcting the genetic mutation responsible for hemophilia and restoring normal clotting function. Clinical trials are underway to evaluate the safety and efficacy of gene therapy approaches, with encouraging results reported thus far.  In conclusion, hemophilia is a complex genetic disorder characterized by impaired blood clotting, leading to prolonged bleeding episodes. While there is currently no cure, ongoing research and advancements in treatment offer hope for improved management and potentially a cure in the future. With early diagnosis, comprehensive care, and support from healthcare providers and advocacy groups, individuals with hemophilia can lead fulfilling lives and minimize the impact of the condition on their daily activities. 3 amazing technologies that made car parking easier Everest will be launched, not Ford Endeavour, will Fortuner's glory end? Electric version of this popular SUV is coming, will run 500km on full charge!

What Causes Hemophilia / Haemophilia?

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knowledge center home » hemophilia » all about hemophilia » causes of hemophilia

People with hemophilia are born with it. It is caused by a fault in one of the genes that determine how the body makes blood clotting factor VIII or IX. These genes are located on the X chromosome.

To understand how hemophilia is inherited, it is important to learn about chromosomes.

What are chromosomes?

Chromosomes are blocks of DNA (deoxyribonucleic acid). They contain very detailed and specific instructions that determine:

How the cells in a baby's body develop.

What features the baby will have, including, for example, hair and eye color.

Whether the baby is male or female.

In humans there are 23 pairs of chromosomes, including the sex chromosome pair. There are two types of sex chromosome:

The X chromosome

The Y chromosome

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All humans have a pair of sex chromosomes:

Males have an X + Y pair

Females have an X + X pair

NB  Females do not have any Y chromosomes.

What chromosomes do we inherit from our parents?

A Male inherits his

X chromosome from his mother

Y chromosome from his father

A Female inherits

One X chromosome from her mother

One X chromosome from her father

She does not inherit both X chromosomes from her mother. She has no Y chromosomes.

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(Before reading on, remember that the faulty gene is never on the Y chromosome. If it is present, it will be on the X chromosome.)

Female (X + Xfaulty) is a carrier, but does not have hemophilia. The "good" X chromosome allows the production of enough clotting factor to prevent serious bleeding problems.

Male (Y + Xfaulty) will develop hemophilia and can pass it on.

If the father has hemophilia and the mother has no faulty gene (is not a carrier):

Father (Y + Xfaulty). Mother (X + X).

There is no risk of inherited hemophilia in their sons because boys will inherit their X chromosome from the mother, not the father (they inherit the father's Y chromosome only, which does not have the faulty gene).

All the daughters will be carriers but will not develop hemophilia although they will inherit the father's X chromosome, which has the faulty gene. However, their maternal X chromosome, which does not have the faulty gene, usually allows the production of enough clotting factor to prevent serious bleeding problems.

If the father does not have hemophilia and the mother has a faulty gene:Father (Y + X). Mother (X + Xfaulty).

There is a 50% chance that sons will develop hemophilia because:

There is a 50% risk that a son will inherit his mother's Xfaulty chromosome, plus his father's Y chromosome - he will have hemophilia.

There is a 50% chance he will inherit his mother's "good" X chromosome, plus his father's Y chromosome - he will not have hemophilia.

There is a 50% chance that daughters will be carriers, (but no chance of developing hemophilia), because:

There is a 50% chance she will inherit her mother's Xfaulty chromosome, making her a carrier.

There is a 50% chance she will inherit her mother's "good" X chromosome, which would mean she would not be a carrier.

Approximately one third of patients with hemophilia have no family history of the disease, either because of new genetic mutations, or because previous affected generations either had daughters (who were carriers) or sons who died in early childhood from hemophilia or any other cause or who were not affected.

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Pfizer Wins Approval For $3.5m Hemophilia B Gene Therapy

DepositPhotos/DmytroKozak

"Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular factor IX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues," said Adam Cuker, director Penn Comprehensive and Hemophilia Thrombosis Program. "A one-time treatment with Beqvez has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term."

The gene therapy is the third such product approved by the US Food and Drug Administration (FDA), following the November 2022 approval of CSL Behring's Hemgenix (etranacogene dezaparvovec) – also for hemophilia B – and the July 2023 approval of BioMarin's Roctavian (valoctocogene roxaparvovec) for hemophilia A.

While there are two one-time therapies now available, the standard of care for hemophilia B treatment continues to be prophylactic infusions of factor XI replacement therapy, which temporarily replaces or supplements low levels of blood-clotting factor.

Pfizer has set a list price of $3.5 million for Beqvez, matching the wholesale acquisition cost of Hemgenix.

Pfizer licensed the Beqvez from gene therapy pioneer Spark Therapeutics (now part of Roche) in December 2014. The therapy forms part of the Big Pharma's gene therapy ambitions, which has been built out through the acquisition of Bamboo Therapeutics in 2016 and a collaboration with Sangamo Therapeutics in 2020. The former added a candidate for Duchenne Muscular Dystrophy (DMD), while the latter focuses on hemophilia A.

The firm has also bulked out its manufacturing network to support gene therapies through an $800 million (originally $500 million) investment, which included the construction of an 85,500 square-foot plant in Durham, North Carolina to support clinical manufacturing.

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