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.