Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but which contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. [1] It is the intravascular part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains important dissolved proteins (6–8%; e.g., serum albumins, globulins, and fibrinogen), [2] glucose, clotting factors, electrolytes (Na+
, Ca2+
, Mg2+
, HCO3−, Cl−
, etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and oxygen. [3] It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders. [4]
Blood plasma can be separated from whole blood through blood fractionation, by adding an anticoagulant to a tube filled with blood, which is spun in a centrifuge until the blood cells fall to the bottom of the tube. The blood plasma is then poured or drawn off. [5] For point-of-care testing applications, plasma can be extracted from whole blood via filtration [6] or via agglutination [7] to allow for rapid testing of specific biomarkers. Blood plasma has a density of approximately 1,025 kg/m3 (1.025 g/ml). [8] Blood serum is blood plasma without clotting factors. [5] Plasmapheresis is a medical therapy that involves blood plasma extraction, treatment, and reintegration.
Fresh frozen plasma is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. [9] It is of critical importance in the treatment of many types of trauma which result in blood loss, and is therefore kept stocked universally in all medical facilities capable of treating trauma (e.g., trauma centers, hospitals, and ambulances) or that pose a risk of patient blood loss such as surgical suite facilities. [10]
Blood plasma volume may be expanded by or drained to extravascular fluid when there are changes in Starling forces across capillary walls. For example, when blood pressure drops in circulatory shock, Starling forces drive fluid into the interstitium, causing third spacing. [11]
Standing still for a prolonged period will cause an increase in transcapillary hydrostatic pressure. As a result, approximately 12% of blood plasma volume will cross into the extravascular compartment. This plasma shift causes an increase in hematocrit, serum total protein, blood viscosity and, as a result of increased concentration of coagulation factors, it causes orthostatic hypercoagulability. [12]
Serum albumins are the most common plasma proteins, and they are responsible for maintaining the osmotic pressure of the blood. Without albumins, the consistency of blood would be closer to that of water. The increased viscosity of blood prevents fluid from entering the bloodstream from outside the capillaries. Albumins are produced in the liver, assuming the absence of a hepatocellular deficiency. [13]
The second most common type of protein in the blood plasma are globulins. Important globulins include immunoglobins which are important for the immune system and transport hormones and other compounds around the body. There are three main types of globulins. Alpha-1 and Alpha-2 globulins are formed in the liver and play an important role in mineral transport and the inhibition of blood coagulation. [14] An example of beta globulin found in blood plasma includes low-density lipoproteins (LDL) which are responsible for transporting fat to the cells for steroid and membrane synthesis. [15] Gamma globulin, better known as immunoglobulins, are produced by plasma B cells, and provides the human body with a defense system against invading pathogens and other immune diseases. [16]
Fibrinogen proteins make up most of the remaining proteins in the blood. Fibrinogens are responsible for clotting blood to help prevent blood loss. [17]
Plasma is normally yellow due to bilirubin, carotenoids, hemoglobin, and transferrin. [18] In abnormal cases, plasma can have varying shades of orange, green, or brown. The green color can be due to ceruloplasmin or sulfhemoglobin. The latter may form due to medicines that are able to form sulfonamides once ingested. [19] A dark brown or reddish color can appear due to hemolysis, in which methemoglobin is released from broken blood cells. [20] Plasma is normally relatively transparent, but sometimes it can be opaque. Opaqueness is typically due to elevated content of lipids like cholesterol and triglycerides. [21]
Plasma and serum are both derived from full blood, but serum is obtained by removing blood cells, fibrin clots, and other coagulation factors while plasma is obtained by only removing blood cells [22] . Blood plasma and blood serum are often used in blood tests. Tests can be done on plasma, serum or both. [23] In addition, some tests have to be done with whole blood, such as the determination of the amount of blood cells in blood via flow cytometry. [24]
Plasma preparation is quick, as it is not coagulated. Serum sample preparation requires about 30 minutes of waiting time before it can be centrifuged and then analyzed. [23] However, coagulation can be hastened down to a few minutes by adding thrombin or similar agents to the serum sample. [25]
Compared to serum, 15–20% larger volume of plasma can be obtained from a blood sample of certain size. Serum lacks some proteins that partake in coagulation and increase the sample volume. [23]
Serum preparation can cause measurement errors by increasing or decreasing the concentration of the analyte that is meant to be measured. For example, during coagulation, blood cells consume blood glucose and platelets increase the sample content of compounds like potassium, phosphates and aspartate transaminase by secreting them. Glucose or these other compounds may be the analytes. [23]
Plasma preparation requires the addition of anticoagulants, which can cause expected and unexpected measurement errors. For example, anticoagulant salts can add extra cations like NH4+, Li+, Na+ and K+ to the sample, [23] or impurities like lead and aluminum. [26] Chelator anticoagulants like EDTA and citrate salts work by binding calcium (see carboxyglutamic acid), but they may also bind other ions. Even if such ions are not the analytes, chelators can interfere with enzyme activity measurements. For example, EDTA binds zinc ions, which alkaline phosphatases need as cofactors. Thus, phosphatase activity cannot be measured if EDTA is used. [23]
An unknown volume of anticoagulants can be added to a plasma sample by accident, which may ruin the sample as the analyte concentration is changed by an unknown amount. [26]
No anticoagulants are added to serum samples, which decreases the preparation cost of the samples relative to plasma samples. [26]
Plasma samples can form tiny clots if the added anticoagulant is not properly mixed with the sample. Non-uniform samples can cause measurement errors. [26]
Plasma was already well known when described by William Harvey in de Motu Cordis in 1628, but knowledge of it probably dates as far back as Vesalius (1514–1564). The discovery of fibrinogen by William Henson, c. 1770, [27] made it easier to study plasma, as ordinarily, upon coming in contact with a foreign surface – something other than the vascular endothelium – clotting factors become activated and clotting proceeds rapidly, trapping RBCs etc. in the plasma and preventing separation of plasma from the blood. Adding citrate and other anticoagulants is a relatively recent advance. Upon the formation of a clot, the remaining clear fluid (if any) is blood serum, which is essentially plasma without the clotting factors [28]
The use of blood plasma as a substitute for whole blood and for transfusion purposes was proposed in March 1918, in the correspondence columns of the British Medical Journal, by Gordon R. Ward. "Dried plasmas" in powder or strips of material format were developed and first used in World War II. Prior to the United States' involvement in the war, liquid plasma and whole blood were used. [29]
Dr. José Antonio Grifols Lucas, a scientist from Vilanova i la Geltrú, Spain, [30] founded Laboratorios Grifols in 1940. [31] Dr. Grifols pioneered a first-of-its-kind technique called plasmapheresis, [31] where a donor's red blood cells would be returned to the donor's body almost immediately after the separation of the blood plasma. This technique is still in practice today, almost 80 years later. In 1945, Dr. Grifols opened the world's first plasma donation center. [30]
The "Blood for Britain" program during the early 1940s was quite successful (and popular in the United States) based on Charles Drew's contribution. A large project began in August 1940 to collect blood in New York City hospitals for the export of plasma to Britain. Drew was appointed medical supervisor of the "Plasma for Britain" project. His notable contribution at this time was to transform the test tube methods of many blood researchers into the first successful mass production techniques. [32]
Nevertheless, the decision was made to develop a dried plasma package for the armed forces as it would reduce breakage and make the transportation, packaging, and storage much simpler. [33] The resulting dried plasma package came in two tin cans containing 400 cc bottles. One bottle contained enough distilled water to reconstitute the dried plasma contained within the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. The Blood for Britain program operated successfully for five months, with total collections of almost 15,000 people donating blood, and with over 5,500 vials of blood plasma. [34]
Following the Supplying Blood Plasma to England project, Drew was named director of the Red Cross blood bank and assistant director of the National Research Council, in charge of blood collection for the United States Army and Navy. Drew argued against the armed forces directive that blood/plasma was to be separated by the race of the donor. Drew insisted that there was no racial difference in human blood and that the policy would lead to needless deaths as soldiers and sailors were required to wait for "same race" blood. [35]
By the end of the war the American Red Cross had provided enough blood for over six million plasma packages. Most of the surplus plasma was returned to the United States for civilian use. Serum albumin replaced dried plasma for combat use during the Korean War. [33]
Plasma as a blood product prepared from blood donations is used in blood transfusions, typically as fresh frozen plasma (FFP) or Plasma Frozen within 24 hours after phlebotomy (PF24). When donating whole blood or packed red blood cell (PRBC) transfusions, O- is the most desirable and is considered a "universal donor," since it has neither A nor B antigens and can be safely transfused to most recipients. Type AB+ is the "universal recipient" type for PRBC donations. However, for plasma the situation is somewhat reversed. Blood donation centers will sometimes collect only plasma from AB donors through apheresis, as their plasma does not contain the antibodies that may cross react with recipient antigens. As such, AB is often considered the "universal donor" for plasma. Special programs exist just to cater to the male AB plasma donor, because of concerns about transfusion related acute lung injury (TRALI) and female donors who may have higher leukocyte antibodies. [36] However, some studies show an increased risk of TRALI despite increased leukocyte antibodies in women who have been pregnant. [37]
Following fears of variant Creutzfeldt-Jakob disease (vCJD) being spread through the blood supply, the British government began to phase out blood plasma from U.K. donors and by the end of 1999 had imported all blood products made with plasma from the United States. [38] In 2002, the British government purchased Life Resources Incorporated, an American blood supply company, to import plasma. [39] The company became Plasma Resources UK (PRUK) which owned Bio Products Laboratory. In 2013, the British government sold an 80% stake in PRUK to American hedge fund Bain Capital, in a deal estimated to be worth £200 million. The sale was met with criticism in the UK. [40] In 2009, the U.K. stopped importing plasma from the United States, as it was no longer a viable option due to regulatory and jurisdictional challenges. [41]
At present (2024), blood donated in the United Kingdom is used by UK Blood Services for the manufacture of plasma blood components (Fresh Frozen Plasma (FFP) and cryoprecipitate). However, plasma from UK donors is still not used for the commercial manufacture of fractionated plasma medicines. [42]
Simulated body fluid (SBF) is a solution having a similar ion concentration to that of human blood plasma. SBF is normally used for the surface modification of metallic implants, and more recently in gene delivery application. [43]
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.
Clinical chemistry is a division in medical laboratory sciences focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using analytical techniques and specialized instruments. This interdisciplinary field includes knowledge from medicine, biology, chemistry, biomedical engineering, informatics, and an applied form of biochemistry.
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, plasma, platelets, and other clotting factors. White blood cells are transfused only in very rare circumstances, since granulocyte transfusion has limited applications. Whole blood has come back into use in the trauma setting.
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.
Serum protein electrophoresis is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a monoclonal gammopathy of uncertain significance (MGUS), or further investigate a discrepancy between a low albumin and a relatively high total protein. Unexplained bone pain, anemia, proteinuria, chronic kidney disease, and hypercalcemia are also signs of multiple myeloma, and indications for SPE. Blood must first be collected, usually into an airtight vial or syringe. Electrophoresis is a laboratory technique in which the blood serum is applied to either an acetate membrane soaked in a liquid buffer, or to a buffered agarose gel matrix, or into liquid in a capillary tube, and exposed to an electric current to separate the serum protein components into five major fractions by size and electrical charge: serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma globulins.
Serum is the fluid and solvent component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum contains all proteins except clotting factors, including all electrolytes, antibodies, antigens, hormones; and any exogenous substances. Serum also does not contain all the formed elements of blood, which include blood cells, white blood cells, red blood cells (erythrocytes), and platelets.
An automated analyser is a medical laboratory instrument designed to measure various substances and other characteristics in a number of biological samples quickly, with minimal human assistance. These measured properties of blood and other fluids may be useful in the diagnosis of disease.
A blood bank is a center where blood gathered as a result of blood donation is stored and preserved for later use in blood transfusion. The term "blood bank" typically refers to a department of a hospital usually within a clinical pathology laboratory where the storage of blood product occurs and where pre-transfusion and blood compatibility testing is performed. However, it sometimes refers to a collection center, and some hospitals also perform collection. Blood banking includes tasks related to blood collection, processing, testing, separation, and storage.
The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune system. Globulins, albumins, and fibrinogen are the major blood proteins. The normal concentration of globulins in human blood is about 2.6-3.5 g/dL.
Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood proteins act as enzymes, complement components, protease inhibitors or kinin precursors. Contrary to popular belief, haemoglobin is not a blood protein, as it is carried within red blood cells, rather than in the blood serum.
Apheresis is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation. It is thus an extracorporeal therapy.
Plasmapheresis is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulation. It is thus an extracorporeal therapy, a medical procedure performed outside the body.
The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.
Fresh frozen plasma (FFP) is a blood product made from the liquid portion of whole blood. It is used to treat conditions in which there are low blood clotting factors or low levels of other blood proteins. It may also be used as the replacement fluid in plasma exchange. Using ABO compatible plasma, while not required, may be recommended. Use as a volume expander is not recommended. It is administered by slow injection into a vein.
Intraoperative blood salvage (IOS), also known as cell salvage, is a specific type of autologous blood transfusion. Specifically IOS is a medical procedure involving recovering blood lost during surgery and re-infusing it into the patient. It is a major form of autotransfusion.
The thrombin time (TT), also known as the thrombin clotting time (TCT), is a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added. It is used to diagnose blood coagulation disorders and to assess the effectiveness of fibrinolytic therapy. This test is repeated with pooled plasma from normal patients. The difference in time between the test and the 'normal' indicates an abnormality in the conversion of fibrinogen to fibrin, an insoluble protein.
Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.
An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient.
The liver plays the major role in producing proteins that are secreted into the blood, including major plasma proteins, factors in hemostasis and fibrinolysis, carrier proteins, hormones, prohormones and apolipoprotein: