What is Hemophilia?

Hemophilia is very rare -- only about 20,000 Americans have the disorder.

It affects mostly males, as it is an X chromosome linked condition. Hemophilia affects 1 in 5,000 male births in the U.S. and approximately 400 babies are born with hemophilia each year. 400,000 people worldwide are living with hemophilia and about 20,000 are living with it in the United States alone. All races and economic groups are affected equally. People with hemophilia who have access to factor replacement therapy have a normal life expectancy.

Types of Hemophilia

Bleeding disorders are treated differently depending on what protein is missing in the blood. Hemophilia is one of the most common bleeding disorders and is classified as follows:

  • Hemophilia A – Also called classic hemophilia, it is 4 times more common than hemophilia B, and it occurs when factor VIII levels are deficient.

  • Hemophilia B – Also called Christmas disease, it occurs when factor IX levels are deficient.

  • Hemophilia C – It occurs when factor XI levels are deficient

  • Acquired hemophilia – A person can develop hemophilia as a result of illness, medications, or pregnancy. Acquired hemophilia is extremely rare and usually resolves itself with proper diagnosis and treatment.

Severity of the Disorder

Severity
Hemophilia A and B                        Range

Normal factor levels                        50% – 150%

Mild hemophilia                               5% – 49%

Moderate hemophilia                      1%-5%

Severe hemophilia                          Less than 1%

Symptoms of Hemophilia

A person with hemophilia can bleed inside or outside of the body. People with hemophilia do not bleed more than people without hemophilia, they just bleed longer. The most common types of bleeds are into the joints and muscles. Other symptoms include:

  • Nose bleeds

  • Prolonged bleeding from minor cuts

  • Bleeding that stops and resumes after stopping for only a short time

  • Blood in the urine

  • Blood in the stool

  • Large bruises

  • Hematomas

  • Easy bruising (unexplained bruising)

  • Excessive bleeding with dental work or tooth extraction

  • Heavy periods and/or periods lasting more than 7 days

               Causes of Hemophilia

A person is born with hemophilia. Hemophilia cannot be caught from someone else and it cannot spread like a virus or an infection. The gene that contains the instructions to properly make factor VIII and IX exist in the X chromosome.

Hemophilia is caused when the gene inside the X chromosome is defective. Males have one Y and one X chromosome. Therefore, since a male’s DNA contains only one X chromosome, hemophilia affects mostly males. Women have two X chromosomes, so even if one has a defective gene, the other X chromosome has the information needed to create clotting factors. A female can have Hemophilia because of X-inactivation or Lyonization. It is possible for one X to “shut-down” or not to express itself. If the X chromosome with the Hemophilia gene is the active chromosome than she will have lower levels. 50% of carriers have low factor levels. Hemophilia may be inherited, or it may be caused by a spontaneous mutation of the factor gene.

Inherited hemophilia

In 70% of cases of hemophilia, there is a known family history. The gene that causes hemophilia is passed from mother to child. A mother that carries the gene is called a carrier. A carrier has a 50% chance of having a son with hemophilia and a 50% chance of having a daughter who is also a carrier. In other words, a female carrier has a 25% chance of having a child with hemophilia. 

Spontaneous Mutations

Approximately 30% of cases of hemophilia are caused by a spontaneous mutation of the gene. In these cases, the mother is not a carrier of hemophilia and the child affected is the first in the family to have hemophilia and to carry the defective factor gene.

Carrier

A female who has a defect in one of her X chromosomes is said to be a carrier of hemophilia. She carries the gene that may be passed to her children. A mother may be a carrier and may not know that she is a carrier if there is no family history of the condition.

Carrier Testing

A mother who has a son with hemophilia and who has no family history of the condition may or may not be a carrier of hemophilia. A mother who has a son with hemophilia should consider having her factor levels tested. She may have low factor VIII or factor IX levels, and that information could be critical in her well-being in cases of surgery or severe trauma. It is advisable that a mother who has a son with hemophilia be tested for her son’s genetic mutation to see if she is a carrier of hemophilia. This information is important when planning subsequent pregnancies, and may be necessary to share with other female family members who are thinking of having children.

Symptomatic Carriers

A carrier of hemophilia who experiences some bleeding symptoms is called a symptomatic carrier. Some carrier females have low factor levels and they may be considered to have mild hemophilia. Symptomatic carriers often experience frequent nose bleeds, heavy menstrual periods, and easy bruising.

        Treatment of Hemophilia

The preferred treatment for hemophilia is factor replacement therapy. Hemophilia is treated by injecting the missing factor protein into the affected person’s vein. The injection makes the factor immediately available in the bloodstream and the body is able to activate it to continue the clotting cascade and stop the bleeding.

Products

Hemophilia is treated by replacing the protein that is missing in the blood. In the United States, there are two types of products used to treat hemophilia today:

The preferred treatment for hemophilia is factor replacement therapy. Hemophilia is treated by injecting the missing factor protein into the affected person’s vein. The injection makes the factor immediately available in the bloodstream and the body is able to activate it to continue the clotting cascade and stop the bleeding. There are two types of products used to treat hemophilia today:

Plasma-Derived Products

These are factor concentrates that are made from human blood. Blood contains plasma, which contains proteins, antibodies, albumin and clotting factors. Plasma- derived products are made with donated blood plasma that is carefully screened. During the manufacturing process, the proteins extracted from the plasma go through a series of extensive sterilization procedures to eliminate viruses and other contaminants.

Recombinant Factor Concentrates

These products are manufactured using hamster cells. Manufacturers inject hamster cells with the factor gene so that large amounts of the factor protein can be produced. Since the proteins are extracted from animal cells, they do not contain human viruses. Some factor concentrate products are stabilized using human albumin, while others are stabilized using sucrose.

      Frequency of Infusions

The frequency of treatment is determined based on the bleeding pattern and severity of the disorder. There are two types of therapies to consider:

Prophylaxis

People on prophylaxis infuse their treatment on a regular schedule to prevent bleeds from occurring. Prophylaxis is recommended for children with severe hemophilia. There are two types of prophylaxis:

  • Primary – This type of treatment is usually started in young children to reduce or prevent joint disease and it is continued indefinitely.

  • Secondary – This type of prophylaxis is usually short term and it is started when a bleed has occurred and continued on a regular schedule for a defined period of time.

There are advantages and disadvantages that need to be reviewed when determining the best treatment for an individual:

Advantages:

  • Reduced risk of joint damage

  • Ability to participate in sports and other physical activities

  • Reduced risk of spontaneous bleeding

Disadvantages:

  • Frequent injections

  • Cost – Factor replacement is very expensive. An average prophylactic dose is 25 units per kilo. Each unit costs approximately $1. For example, an adult weighing 150 lbs., would inject 1,700 units per dose. This equals a cost of approximately $1,700 per dose.

On Demand

This treatment is on an “as needed basis” to treat active bleeding. Factor replacement is injected into the vein after an injury has occurred. There are advantages and disadvantages that need to be reviewed when determining the best treatment for an individual:

Advantages:

  • Less injections

  • Less cost

Disadvantages:

  • Increased risk of joint damage

  • Increased risk of spontaneous bleeds

        Infusion Methods

All products available to treat hemophilia need to be injected directly into the bloodstream. There are several options to infuse the factor product into the bloodstream, and each has its advantages and disadvantages:

Peripheral Vein Access

A butterfly needle is used to inject the factor into the bloodstream. Below are some considerations regarding this type of access:

  • Requires a clean technique to be used. Sterile technique is not necessary.

  • Low risk of infection when clean technique is used

  • Treatment is completed fairly quickly if the person’s veins are large and easy to find

  • Children’s veins are often too small and difficult to find

Port-a-catheter

The port is a device that is surgically implanted under the skin and it is connected to a central vein with catheter tubing under the chest. A few things to consider:

  • The port can be accessed repeatedly for many years.

  • Provides a large area where the needle can be placed to infuse factor.

  • The port must be accessed using sterile technique to avoid infection.

  • Children can participate in water activities, as the port is under the skin.

  • The port looks like a large mosquito bite (the size of a quarter) under the skin.

  • Infection: The main risk of a port is the risk of infection.

  • Clotting: A clot may form within the catheter.

Peripherally inserted central catheter (PICC)

A catheter is inserted into a vein in the arm and is connected to a blood vessel in the chest. Part of the catheter stays on the outside of the arm and infusions are done through that device. This device is easy to use and no sticks into the person’s skin are necessary. However, PICC lines only last a few weeks or months.

Dosage

Factor dosage is determined based on weight, type of disorder, severity, and the type of bleeding episode the person is experiencing. A hematologist will calculate dosage needed for major, minor and prophylactic doses. The dosage will be indicated in units of factor. In addition, dosage may be adjusted based on how the person’s body uses the factor product.

 

Factor concentrates are measured in units. One unit is equivalent to the amount of factor activity found in 1 cc or 1 ml of fresh plasma. Factor products are delivered in glass vials with labels indicating the number of units per vial. Manufacturing companies produce common size vials but at times, depending on body weight, a person may need to mix more than one vial to achieve the necessary dosage.

 

Factor VIII and factor IX dosages are calculated differently because the amount of factor units needed to raise one kilogram of weight to normal level activity is different. Factor VIII products indicate that 50 units (.5 IU/Kg) are needed to raise one kilogram of weight to normal range activity while factor IX products indicate that 100 units (1 IU/Kg) are needed per kilogram.

The formula to calculate Factor VIII dosage:

Dosage in Factor VIII units = (Weight in kilograms) x (Factor percentage desired) x .5 (per product indications)

 

(Sample Only. Actual dosing should be determined by doctor and patient based on that individual’s needs.)For example, a person with severe hemophilia A that weighs 120 pounds, or 54 kilograms, (120 ÷ 2.2) may be given the following doses:

 

Type of Bleed                                                           Percentage Needed                     Number of Units

Major Bleeds – head, throat, eye, stomach                      100%                                         2700 units

Minor Bleeds – muscles, joints                                           50%                                         1350 units

 

It is important to note that exact dosage vials are usually not available. However, multiple vials can be mixed to add up to the approximate number of units needed. It is not harmful to infuse more units of factor VIII that needed.

 

Half-life of a product is the amount of time it stays intact until its activity cuts in half. The half-life of factor VIII products available today to treat hemophilia is 12 hours. This means that on average, a dose of factor VIII will stay in the bloodstream at its expected activity level for 12 hours. After that, the activity level will be cut in half every 12 hours.

 

A person may process factor differently, so the 12 hours may vary. Your hematologist may adjust your dosage based on your bleeding history and/or factor level testing.

The formula to calculate Factor IX dosage:

Dosage in Factor VIII units = (Weight in kilograms) x (Factor percentage desired) x 1 (per product indications)

 

(Sample Only. Actual dosing should be determined by doctor and patient based on that individual’s needs.)  For example, a person with severe hemophilia B that weighs 120 pounds, or 54 kilograms, (120 ÷ 2.2) may be given the following doses:

 

Type of Bleed                                                      Percentage Needed                            Number of Units

Major Bleeds – head, throat, eye, stomach                 100%                                              5400 units

Minor Bleeds – muscles, joints                                      50%                                              2700 units

 

It is important to note that exact dosage vials are usually not available. However, multiple vials can be mixed to add up to the approximate number of units needed. For factor IX, it is recommended that the number of units infused does not exceed the dosage prescribed.

 

Half-life of a product is the amount of time it stays intact until its activity cuts in half. The half-life of factor IX products available today to treat hemophilia is 24 hours. This means that on average, a dose of factor IX will stay in the bloodstream at its expected activity level for 24 hours. After that, the activity level will be cut in half every 24 hours.

 

A person may process factor differently, so the 24 hours may vary. Your hematologist may adjust your dosage based on your bleeding history and/or factor level testing.

Medical Professionals

Hematologists are experts in hemophilia and other blood disorders. A hematologist can diagnose, provide guidance, and prescribe the factor concentrate and dosage that is needed to treat bleeds prophylactically or on demand. However, hemophilia is a complex disorder that often requires care from other health professionals, like physical therapists, geneticists, and social workers. In order to facilitate comprehensive care for patients with hemophilia, the United States federal government provides funds that support hemophilia treatment centers (HTCs) in cities across the country. HTCs help coordinate care among medical experts to treat all aspects of hemophilia. Please visit www.cdc.gov to find an HTC near you.

Inheritance Pattern of Hemophilia

The following diagrams show how the hemophilia gene can be inherited. It is important to note that in one-third of people with hemophilia, there is no family history of the disorder.

Mother is a carrier

  • 50% chance that each son will have hemophilia.

  • 50% chance that each daughter will be a carrier of the hemophilia gene.

Father has hemophilia

  • All daughters will carry the hemophilia gene.

  • No sons will have hemophilia.

Mother is a carrier AND

Father has hemophilia

  • 50% chance that each son will have hemophilia.

  • 50% chance that each daughter will be a carrier of the hemophilia gene.

  • 50% chance that each daughter will have hemophilia.

Cited from www.hemophiliafed.org

 
 
 

About us:

Tennessee Hemophilia & Bleeding Disorders Foundation is a non-profit 501(c)(3) organization.  The foundation was founded in 1970.

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