What is Blood Plasma? 

Plasma, in its simplest definition, is the liquid portion of the blood. In most people, plasma contributes the majority of the blood volume. In a normal healthy adult, plasma makes up roughly 55% of the total blood volume, depending on the patients hematocrit. Plasma contains nearly all of the chemical constituents that humans require to live. Electrolytes, glucose, hormones, antibodies, proteins, etc. Plasma is how the body moves all of these chemicals, compounds, proteins and more throughout the body. Plasma physically helps maintain fluid balance, blood pressure, oncotic and osmotic balances within the blood vessel. Plasma contains coagulation enzymes that help your body clot to stop bleeding.  Plasma also helps carry waste to the kidneys and liver to be processed for elimination. Roughly 97% of plasma is made up of water. 

The main proteins found in plasma are albumin, globulins, and coagulation factors. Albumin (specifically human serum albumin) is a protein synthesized in the liver that is used for transporting certain molecules throughout the blood to their intended destinations as well as maintaining the oncotic pressures. The oncotic pressures help to maintain fluid within the blood vessels. Without the aid of albumin, vessels can become 'leaky' and fluid could leave the vessels and leak into other tissues causing edema. Albumin makes up roughly 50-60% of all proteins in the plasma. 

Globulins make up roughly 40 percent of all proteins in the plasma. They are typically broken down into different classes Alpha 1, Alpha 2, Beta, and Gamma globulins. Globulins have a wide array of functions in the body, some are membrane transport proteins, some are enzymes, some are used in blood coagulation, and some are involved in the immune system providing immunity. Immunoglobulin, a type of gamma globulin, is the name for an antibody. There are many types of antibodies as well that provide different levels of protection. 

The remaining plasma proteins involve mostly blood coagulation aids. 5-10% of the remaining proteins in the blood exist as fibrinogen. Fibrinogen is what gets converted to fibrin during the formation of a clot and exists to stabilize and cement a clot in place to prevent bleeding during vascular injury. In addition to fibrinogen, 1% or less of all blood proteins exist as other coagulation factors. There are 12 main coagulation factors (excluding fibrinogen) that are involved in the complex pathways of events that lead to a stabilized clot. 

There are also a very small amount of proteins that exist to regulate gene expression as well. 

Plasma is typically straw yellow in color and mostly transparent. Certain drugs or health conditions can change the color of the plasma. Certain birth control drugs are notorious for giving plasma a greenish hue. Other health conditions, such as having high triglycerides in the blood, can make plasma opaque and less "see-through". This is referred to as lipemia (literally lipids in the blood) Slight lipemia in a unit of plasma is generally acceptable for transfusion, but excessive lipemia would likely be rejected by a blood center. Unfortunately, this would not be noticed until the donation is processed and already completed. 

Plasma Donation and Manufacturing

Units of plasma can typically be made from two types of donation. A whole blood donation in which gravity drains blood into a (usually) 500mL bag. Plasma can also be donated using an apheresis machine. This typically requires an appointment and is done at the blood center. Mobile donation sites typically do not have apheresis machines. These machines can remove a portion of your blood, centrifuge the blood within the machine to separate it into parts, remove the portion that is wanted, and return what is not needed back into the patient. 

With a whole blood donation, the unit of  Whole Blood is centrifuged at the donor center which separates blood into its different parts. One centrifuged there will be a visual layer of both plasma and Red Blood Cells. Red Blood Cells get pushed to the bottom of the bag because they are heavier. Plasma can then be expressed off into another bag. Often times, this new bag will then be centrifuged at a higher speed to remove platelets that are mixed in with the plasma. Unless being used for a product called Liquid Plasma, the plasma bag is then put into a freezer (must be less than -18degC) and is shelf stable for one YEAR post donation. A physician may refer to this plasma product as Fresh Frozen Plasma. Fresh Frozen Plasma is actually a specific plasma product frozen within 8 hours of collection. Other plasma products such as FP24, is plasma frozen within 24 hours of collection. If you want to get even crazier, there's another product known as FP24RT24 which is "Plasma frozen within 24 hours after phlebotomy held at room temperature for up to 24 hours". Many clinicians will simply use the terms plasma or FFP when referring to a unit of plasma.

Once thawed for use, units of plasma are good for five days post-thaw at refrigeration temperature. Some institutions will set their limit at 24 hours post thaw per FDA guidelines, but per the Circular of Information from the American Association of Blood and Biotherapies, a five-day expiration is acceptable and proven safe for transfusion AS LONG AS it is labeled as such --- Thawed Plasma is the designated name for plasma thawed for a 5 day expiration. After this amount of time, the coagulation factors in the unit start to deteriorate and become useless for transfusion. 

A unit of plasma being lowered into the water of a Plasma Thawer. This is the most common method of thawing plasma. Constant up-and-down agitation in roughly 37degC (98.6degF) water thaws a unit of plasma in 20-30 minutes depending on the size of the unit. Water temperatures warmer than 37degC run the risk of destroying the heat sensitive proteins in the plasma. 

Plasma compatibility 

Plasma must be given according to compatible blood types, just like Red Blood Cells. Since plasma contains isoagglutinins (innate antibodies in a persons plasma that would attack red blood cells of an incompatible blood type) it is important to match properly. The universal donor and recipients of plasma are the reverse of Red Blood Cells. With Red Blood cells, O is the "universal donor" and AB is the universal recipient. With plasma, AB is the universal donor and O is the "universal recipient". Matching Rh (positive or negative) does not matter with plasma, as there are no Red Cells in the bag to cause a potential reaction. 

Plasma ABO Compatibility

Plasma transfusion

A physician will order plasma to be transfused for many reasons and conditions.

Liver failure -- patients with liver failure whether its alcohol related, autoimmune, viral, may need plasma transfusions if their disease is severe enough. The liver makes the majority of the bodies proteins. A patient without a functioning liver will see decreases in plasma albumin, fibrinogen, clotting factors, etc. All of this leads to a higher risk of bleeding. While efforts have been made to create albumin and fibrinogen IV or injectable infusions, patients in an inpatient setting with severe disease may still benefit from plasma transfusion due to containing ALL of the coagulation factors and not just a select few. Routine plasma administration is not usually recommended in these patients, but if the patient is admitted to an inpatient ward with a severe disease state it may be warranted. 

Warfarin reversal -- plasma may be used in situations where Warfarin (coumadin) anticoagulation needs to be emergently reversed, such as a need for emergent surgery or accidental overdose. Warfarin reversal procedures should also include other reversal drugs and mechanisms where available. Warfarin acts on an enzyme that lowers available Vitamin K1 which in turn lowers the activity of certain coagulation factors. Plasma transfusion can rapidly replenish these coagulation factors in an emergency. 

Multiple coagulation factor deficiencies -- patients with deficiencies in MULTIPLE coagulation factors and have an active bleed or going for emergency surgery would benefit from plasma transfusion. Multiple coag factor deficiencies can be acquired or genetic. Patient's with single coagulation deficiencies would benefit from receiving a recombinant IV injectable form of a coagulation factors. For example, patients with hemophilia A can receive an IV injection of factor VIII, which is the coagulation factor they would be deficient in. Plasma MAY be given in situations where single factor injections are not available for single factor deficiencies. 

Bleeding --- Excessive bleeding, especially from trauma can use up coagulation factors in the bodies attempt to the control the bleed. This in turn causes a coagulopathy in which there is continued impaired blood clotting ability. Patients presenting with a massive hemorrhage should receive plasma at a one to one ratio with Red Blood Cells. That is, during uncontrolled hemorrhage, for every unit of Red Blood Cells received, a unit of plasma should be transfused as well. This ensures the proper ratio of blood within the patient and gives the best chance of achieving hemostasis. 

DIC -- or Disseminated Intravascular Coagulation. DIC is a condition in which the normal balance of the bodies coagulation system is thrown off and the body begins to form clots throughout the vasculature, which can lead to organ damage by cutting off blood flow. As the body continuously forms clots, it uses up the platelets, fibrinogen, and other coagulation factors in the process. As a result, bleeding in other areas of the body results from the inability to maintain proper clotting where necessary. Thus, DIC will and can present with both clotting and bleeding making it a very serious disease. Plasma is generally given in these circumstances to attempt to replenish the body with lost coagulation factors to prevent additional bleeding from occurring. DIC can be triggered by numerous situations such as sepsis (especially bacterial), pregnancy, trauma, cancer, surgery, liver disease, certain drugs, etc.

Burns -- severe burns can create a condition known as Burn Shock. Burn shock can lead to hypovolemia and an extreme immune response which results in fluid leakage from capillaries into the tissues leading to a decrease in overall blood volume (among many other issues). Plasma may be administered to counteract this decrease in blood volume and to help with some of the effects. The coagulation factors in plasma can help maintain clotting if shock were to lead to bleeding. Additionally, plasma contains albumin and other components that help heal the endothelium (lining of the blood vessels) which would have been damaged by the burn. Remember, albumin helps to maintain the oncotic pressures within the vessel to keep plasma inside the vessel from leaking out.  

Snake Bites -- some studies have shown that plasma was able to reverse the coagulopathy seen in snake bite victims, lessening the amount of vials of antivenom needed.

TTP - Thrombotic thrombocytopenic purpura. A condition in which the body lacks an essential enzyme called ADAMTS13, which helps to limit platelets sticking together too much within a vessel. Without ADAMTS13 platelets might over-aggregate within the circulatory system and create clots throughout the body. ADAMTS13 is used to regulate this process. A low level of ADAMTS13 can be genetic or acquired through an autoantibody targeting the enzyme. Patients with TTP benefit from a therapeutic plasma exchange. There are many indications for performing a plasma exchange, some with their individual levels of evidential support. Therapeutic plasma exchanges for treatment in TTP has a grade 1A or high-quality evidence of benefit and efficacy. The procedure involves using an apheresis machine to remove the patients plasma and introduce equal amounts of donor plasma. The donor plasma would be expected to have normal levels of ADAMTS13 thus restoring normal levels, and removing the likelihood of platelet over-aggregation. Typically, plasma exchanges would be done many times, perhaps every day, or every other day until the patient's platelet count improves. Some labs may also test for post-ADAMTS13 levels.

Convalescent Plasma -- COVID19

The Coronavirus pandemic presented a challenge to healthcare agencies across the world. With the desperate need to come up with novel and nascent ideas to aid in healing patients suffering from the COVID-19, came convalescent plasma therapy.  Convalescence refers to the recovery from an illness.  Convalescent plasma has been used in the past prior to antibiotics and antivirals as a way to pass down immunity from a previously infected individual to a current one. The idea is that since the previously infected person has created antibodies towards a particular pathogen, the transfusion of their plasma into a patient has not yet built an immunity (or cannot build a immunity) should create a sort of passive immunity where the antibodies still recognize the pathogen in the recipient and help to destroy the infection. The 1912 Spanish Flu outbreak was the first largescale operation to see the use of convalescent plasma therapy. It was noted that mortality was fairly significantly reduced in those populations who could've used it the most. 

It will likely be some time before data can be properly combed through to get an idea on how much the use of convalescent plasma truly helped during the COVID-19 pandemic. There are many studies that showed that patients had a notable improvement in clinical course, and that thousands of lives were likely saved due to its use. It can also be said that it likely shortened hospital stays as well, opening up beds for those worse off. After vaccine availability, usage plummeted and donation centers such as the American Red Cross stopped collecting for convalescent plasma purposes. However, as the virus mutated and began to evade vaccine coverage, usage of convalescent plasma has started to increase again. Very modestly, however. As of mid to late 2022, most blood centers have discontinued their convalescent plasma collections, due to the stark drop-off in use and the availability of newer vaccines with expanded coverage and other drugs such as the anti-viral Paxlovid.