How plasma-based therapies treat hemophilia

Plasma has been used to treat bleeding disorders like hemophilia since the 1950s, and is still one of the most effective treatment options for patients.


Hemophilia is a genetic disorder that affects the blood's ability to clot and can lead to excessive bleeding, even from minor injuries. In the U.S., there are between 30,000-33,000 people living with hemophilia. The history of treating hemophilia is closely linked to plasma, dating to the 1950s, and plasma is still being used as a treatment for many living with hemophilia today. 

Hemophilia is caused by a variant in one of the genes that codes for clotting factor proteins (either factor VIII or factor IX) needed to form a blood clot. The variant either prevents the clotting protein from working properly or causes it to be missing completely. Individuals with hemophilia A (lacking functional factor VIII) and hemophilia B (lacking functional factor IX) bleed longer than other people. These bleeds can be internal, into joints or muscles, or external, and can be caused by minor injuries or cuts. 

There are three different types and severities of hemophilia: mild, moderate, or severe. 60% of those have severe hemophilia, 15% have moderate hemophilia, and 25% have mild hemophilia. The classification level is dependent on how much of the clotting factor can be found in the patient’s blood. For the average person, a 50%-100% range of factor VIII and factor IX would be considered normal. For those with hemophilia, the ranges are:

  • Mild: 6%-50%
  • Moderate: 1%-5%
  • Severe: <1%

Those with mild hemophilia (6%-50%) will experience infrequent bleeding that typically occurs after injury, trauma, or surgery. These individuals may only have minor bleeding problems.

For moderate hemophilia (1%-5%), bleeding can occur after trauma, surgery, or minor injuries and typically may only bleed one time per month. 

With severe hemophilia (<1%), much like mild and moderate, bleeding can occur after injury, trauma, or surgery, but can also happen spontaneously. These individuals often bleed one or more times a week and may require regular infusions of clotting factors to prevent bleeding episodes. 

Originally, clotting factor products were made primarily from human plasma, although today, many patients use products made through recombinant technology. 

In the late 1950s and into the 1960s, fresh frozen plasma (FFP) was a treatment for hemophilia A and B. There are only small amounts of factors VIII and IX in FFP, so large quantities of plasma had to be infused into patients to stop bleeds. 

In the late 1960s, a method for separating proteins in plasma was developed, allowing scientists and manufacturers to isolate factor VIII and factor IX from pooled plasma–which is the combined plasma of many donors. The factor VIII and factor IX plasma fractions were freeze-dried and labeled to indicate the amount of each factor they contained, which allowed for more accurate dosing.

However, in the 1980s, donated plasma and plasma-derived therapies were discovered to be transmitting potentially deadly blood-borne viruses, like hepatitis and HIV. These events led to the development of the more stringent blood and plasma donation regulations in place today, including viral testing of blood products. Modern regulations help protect not only those donating plasma but those who receive plasma-derived therapies–like people with hemophilia. 

Because of the AIDS epidemic and its threat to the donated plasma people with hemophilia relied on, recombinant clotting factors were developed. Recombinant clotting factors are made in a lab and don't come from plasma donations. They are made with recombinant DNA technology and are concentrated into a powder form that is then mixed with sterile water and injected. While this development has improved the options for treating those with hemophilia, there are still patients who rely on plasma-derived therapies. 

A serious complication in treating hemophilia with either recombinant clotting factors or plasma is the development of inhibitor antibodies created by the body's immune system. These antibodies can reduce the effectiveness of the infused factor used to control or prevent bleeding episodes. Inhibitors do not affect the location, frequency, or severity of bleeds, but they do make them more difficult to control. According to the  Centers for Disease Control and Prevention (CDC), approximately 20% of people with hemophilia A and about 3% of people with hemophilia B will develop inhibitors to their treatment. If a person with hemophilia develops an inhibitor, their body thinks the factor is a foreign substance and tries to destroy it. Signs of an inhibitor include frequent bleeds while on a regular treatment schedule and lack of response to treatment.

There are two types of inhibitors that show up on a Bethesda assay test, which is where inhibitors are measured and given a numeric value that refers to the inhibitor level. The amount of inhibitor in a person’s blood is called a titer. If you have more than 5 Bethesda units, you have a high-titer inhibitor. If you have less than 5 Bethesda units, you have a low-titer inhibitor. Those with low-titer inhibitors will be able to continue using their current treatment but may need to increase the dose. Those with high-titer inhibitors will need to need a new form of treatment. One study shows that there is no greater risk of developing inhibitors if you switch your treatment type.

Another study found that people who were previously untreated and began plasma-derived clotting factor therapy had about a 50% lower rate of developing inhibitors than those who were being treated with recombinant factors. Another study found that switching treatments is an option if significantly influences inhibitor development.

Since there are a variety of therapies for those living with hemophilia and other bleeding disorders, individuals with hemophilia work with their hematologist to find a treatment that works for them. While there are benefits to either treatment, plasma-derived therapy is still a critical and frequently used treatment for hemophilia. 

In fact, it can take upwards of 1,200 plasma donations to treat just one patient with hemophilia for one year. This shows how critical plasma donations truly are for those living with hemophilia, and other chronic, rare disorders. 

Want to hear from someone who understands what it’s like living with hemophilia? Meet Katilin, who donates plasma to help her two young sons, who are both living with hemophilia A. 

Learn more about hemophilia from our friends at the National Hemophilia Foundation (NHF), the World Foundation of Hemophilia (WFH), and the Hemophilia Federation of America (HFA)

Join the Plasma Hero online community

Subscribe to Plasma Hero to get important news and updates that include hero stories and ways to get involved!

Sign up

News & Updates

Get the latest information on plasma through our news and updates. Featuring: Scientific discoveries, plasma supply, industry-related coverage, policy and legislation, and more!

Increase plasma supply by harmonizing state regulations


States with regulations exceeding FDA standards create barriers for plasma centers, donors, and patients.
Read More

Plasma is a vital weapon against tetanus and rabies


While tetanus and rabies are fairly rare in the United States today, these deadly diseases still pose a major global health threat. However, plasma-derived antibody products play a crucial role in treating these illnesses around the world.
Read More

Congressional Plasma Caucus formed to address concerns of constituents


Members of the congressional Plasma Caucus provide a venue to educate legislators on important legislation to provide access to patients who rely on immunoglobulin (Ig) therapy.
Read More

Plasma demand is on the rise because of new patients and products


The need for plasma is forecasted to increase since more patients are being diagnosed with current and newly discovered rare conditions as well as additional indications being approved for plasma medications.
Read More

Busting common plasma donation myths


Misconceptions about plasma donation, such as that it is bad for your health, lead to undue misapprehensions.
Read More

How donated plasma treats trauma and shock


Studies show that giving patients plasma immediately after a traumatic injury improves survival rates significantly.
Read More