While blood transfusions date back to the 1600s, plasma didn't make its way onto the scene until the early 1900s. More precisely, the value of plasma as part of a whole blood transfusion became acutely apparent during the influenza pandemic of 1918. Plasma, which makes up 55% of blood, contains antibodies that fight infections. Whole blood from people who recovered from the 1918 flu, as well as measles and other diseases, was given to people newly infected to help them fight off infections. This crude form of convalescent plasma therapy used whole blood transfusions from recovered flu patients, as scientists hadn’t yet figured out how to separate plasma from blood. Convalescent blood was used as passive immunization before vaccines, which are active immunizations that require the body to produce its own antibodies, became commonplace.
In 1938, Dr Charles Drew discovered how to separate plasma from whole blood while studying the storage and distribution methods of blood at Columbia University. Drew’s novel method was put into practice immediately, as the need for blood and plasma increased at the start of World War II (WWII). One of the reasons plasma was crucial is that it is more shelf-stable and has a longer shelf life than whole blood. Doctors found plasma helpful in treating soldiers for shock during the attack on Pearl Harbor.
Albumin is a protein found in plasma whose function is to maintain appropriate osmotic pressure, as well as bind and transport various substances throughout the body. The albumin in plasma absorbs liquid from surrounding tissues, preventing blood vessels from collapsing, which is commonly associated with shock. By 1944, dried plasma became a vital element in treating wounded soldiers abroad, as well, because it could be stockpiled and shipped anywhere in the world.
Eventually, Dr. Edwin Cohn developed a process called cold ethanol fractionation to break plasma down into its parts, which allowed the albumin to be separated out and used independently. Cohn saved countless lives on the battlefield by discovering how to separate out coagulation or clotting factors (proteins factor VIII and IX) from whole plasma as well. These clotting factors could then be given to wounded soldiers to prevent them from bleeding out, the same reason people with bleeding disorders use plasma today.
When the war ended, the medical community shifted to exploring other uses for plasma. The process of plasma fractionation, first developed by Cohn, led to the development of many plasma-derived treatments used today. The fractionation process was refined from the five major fractions Cohn developed, including albumin, to allow the separation of more proteins found in plasma.
That is how plasma began to be used in 1952 to treat primary immunodeficiencies (PI), a group of more than 450 rare, chronic conditions where a part of the body’s immune system is missing or does not function correctly. Immunoglobulin, the portion of plasma that contains antibodies, provides the immune system properties of a healthy person to someone whose immune system does not make functional antibodies.
At first, immunoglobulin fractionated from whole plasma was administered intramuscularly to those with PI. However, the injections were painful, and only small volumes could be given in each dose. In the 1970s, intravenous immunoglobulin (IVIG) was introduced. This new method of injecting immunoglobulin directly into the bloodstream led doctors to use the treatment more widely, in part because the increased dosing was more clinically successful for a broader scope of disorders. The antibodies found in plasma are metabolized by the body in 3-4 weeks, however, prompting a different form of administration to be developed in 1995 to allow patients to administer their plasma-derived therapy at home using subcutaneous immunoglobulin (SCIG).
In 1961, lack of functional C1-esterase inhibitor, an enzyme that inhibits the first component of the complement cascade in the immune system, was found to be the cause of hereditary angioedema. Plasma quickly became a possible treatment, as C1-esterase inhibitor is found in plasma. Patients given purified plasma-derived human C1 esterase inhibitor concentrate were, for the first time, able to regulate inflammation throughout the body.
You can learn more about some of the people who donate plasma and others who rely on some of the over 50 therapeutic plasma proteins commercially available: https://www.plasmahero.org/hero-stories
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