Blood transfusion is the process of receivingblood products into one's circulationintravenously. Transfusions are used in a variety of 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, white blood cells,plasma, clotting factors, and platelets.
They typically are only recommended when a persons hemoglobin fall below 70-80 mg/dL.One may consider transfusion for people with symptoms of cardiovascular disease such as chest pain or shortness of breath. Globally around 85 units of blood are transfused in a given year.Pre-transfusion procedures
Before a blood transfusion is given, there are many steps taken to ensure quality of the blood products, compatibility, and safety to the recipient.
Blood donation
Blood transfusions typically use two sources of blood: one's own (autologous transfusion), or someone else's (allogeneic transfusion). The latter is much more common than the former. Using another's blood must first start with donation of blood. Blood is most commonly donated as whole blood intravenously and collecting it with ananticoagulant. In developed countries, donations are usually anonymous to the recipient, but products in a blood bank are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. This enables management and investigation of any suspected transfusion related disease transmission ortransfusion reaction. In developing countries the donor is sometimes specifically recruited by or for the recipient, typically a family member, and the donation occurs immediately before the transfusion
Processing and testing of blood products after donation
Donated blood is usually subjected to processing after it is collected, to make it suitable for use in specific patient populations. Collected blood is then separated into blood components by centrifugation: red blood cells, plasma, platelets,albumin protein, clotting factor concentrates,cryoprecipitate, fibrinogen concentrate, andimmunoglobulins (antibodies). Red cells, plasma and platelets can also be donated individually via a more complex process called apheresis.
- All donated blood are tested for infections. The current protocol tests donated blood for HIV-1,HIV-2, HTLV-1, HTLV-2, Hepatitis B, Hepatitis C, Syphilis (T pallidum), Chagas disease (T cruzi), and West Nile Virus. In addition, platelet products are also tested for bacterial infections due to its higher inclination for contamination due to storage at room temperature. Presence of Cytomegalovirus (CMV) is also tested because of risk to certain immunocompromised recipients if given, such as those with organ transplant or HIV. However, not all blood is tested for CMV because only a certain amount of CMV-negative blood needs to be available to supply patient needs. Other than positivity for CMV, any products tested positive for infections are not used.
- All donated blood are also tested for ABO and Rh groups, along with the presence of any red blood cell antibodies.
- Leukoreduction is the removal of white blood cells by filtration. Leukoreduced blood products are less likely to cause HLA alloimmunization (development of antibodies against specific blood types), febrile non-hemolytic transfusion reactions, cytomegalovirus infections, and platelet-transfuion refractoriness.
- Pathogen Reduction treatment that involves, for example, the addition of riboflavin with subsequent exposure to UV light has been shown to be effective in inactivating pathogens (viruses, bacteria, parasites and white blood cells) in blood products. By inactivating white blood cells in donated blood products, riboflavin and UV light treatment can also replace gamma-irradiation as a method to prevent graft-versus-host disease (TA-GVHD)
Compatibility testing
ABO blood group system
Rh blood group system
Before a recipient receives a transfusion, compatibility testing between donor and recipient blood must be done. The first step before a transfusion is given is to Type and Screen the recipient's blood. Typing of recipient's blood determines the ABO and Rh status. The sample is then Screened for any alloantibodies that may react with donor blood. It takes about 45 minutes to complete (depending on the method used). The blood bank technologist also checks for special requirements of the patient (e.g. need for washed, irradiated or CMV negative blood) and the history of the patient to see if they have a previously identified antibody.
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A positive screen warrants an antibody panel/investigation to determine if it is clinically significant. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for commonly encountered and clinically significant alloantibodies. Donor cells may have homozygous (e.g. K+k-), heterozygous (K+k+) expression or no expression of various antigens (K-k+). The phenotypes of all the donor cells being tested are shown in a chart. The patient's serum is tested against the various donor cells using an enhancement method, e.g. Gel or LISS. Based on the reactions of the patient's serum against the donor cells, a pattern will emerge to confirm the presence of one or more antibodies. Not all antibodies are clinically significant (i.e. cause transfusion reactions, HDN, etc.). Once the patient has developed a clinically significant antibody it is vital that the patient receive antigen negative phenotyped red blood cells to prevent future transfusion reactions. A direct antiglobulin test (Coombs test) is also performed as part of the antibody investigation.
If there is no antibody present, an immediate spin crossmatch or computer assisted crossmatch is performed where the recipient serum and donor serum are incubated. In the immediate spin method, two drops of patient serum are tested against a drop of 3-5% suspension of donor cells in a test tube and spun in a serofuge. Agglutination or hemolysis (i.e., positive Coombs test) in the test tube is a positive reaction and the unit should not be transfused.
If an antibody is suspected, potential donor units must first be screened for the corresponding antigen by phenotyping them. Antigen negative units are then tested against the patient plasma using an antiglobulin/indirect crossmatch technique at 37 degrees Celsius to enhance reactivity and make the test easier to read.
In urgent cases where crossmatching cannot be completed, and the risk of dropping hemoglobin outweighs the risk transfusing uncrossmatched blood, O-negative blood is used, followed by crossmatch as soon as possible. O-negative is also used for children and women of childbearing age. It is preferable for the laboratory to obtain a pre-transfusion sample in these cases so a type and screen can be performed to determine the actual blood group of the patient and to check for alloantibodies.
Neonatal transfusion
To ensure the safety of blood transfusion to pediatric patients, hospitals are taking additional precaution to avoid infection and prefer to use specially tested pediatric blood units that are guaranteed negative for Cytomegalovirus. Most guidelines recommend the provision of CMV-negative blood components and not simply leukoreduced components for newborns or low birthweight infants in whom the immune system is not fully developed. These specific requirements place additional restrictions on blood donors who can donate for neonatal use. vnv Neonatal transfusions typically fall into one of two categories:
- "Top-up" transfusions, to replace losses due to investigational losses and correction of anemia.
- Exchange (or partial exchange) transfusions are done for removal of bilirubin, removal of antibodies and replacement of red cells (e.g., for anemia secondary to thalassemias and other hemoglobinopathies).
Procedures
Massive transfusion protocol
A massive transfusion protocol is typically defined as when it is anticipated that more than ten units of packed red blood cells will be needed.Typically higher ratios of fresh frozen plasma
and platlets are given relative to pakes red blood cells.
Adverse effects
Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is also increasing focus (and controversy) on complications arising directly or indirectly from potential quality degradation during storage.Overall, adverse events from transfusions in the US account for about $17Billion - and in effect add more to the cost of each transfusion than acquisition and procedure costs combined.While some complication risks depend on patient status or specific transfusion quantity involved, a baseline risk of complications simply increases in direct proportion to the frequency and volume of transfusion.
Immunologic
- Acute hemolytic reactions occur with transfusion of red blood cells, and occurs in about 0.016 percent of transfusions, with about 0.003 percent being fatal. This is due to destruction of donor erythrocytes by preformed recipient antibodies. Most often this occurs due to clerical errors or improper typing and crossmatching. Symptoms include fever, chills, chest pain, back pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop in blood pressure. When suspected, transfusion should be stopped immediately, and blood sent for tests to evaluate for presence of hemolysis. Treatment is supportive. Kidney injury may occur due to the effects of the hemolytic reaction (pigment nephropathy).
- Delayed hemolytic reactions occur more frequently (about 0.025 percent of transfusions) and are due to the same mechanism as in acute hemolytic reactions. However, the consequences are generally mild and a great proportion of patients may not have symptoms. However, evidence of hemolysis and falling hemoglobin levels may still occur. Treatment is generally not needed, but due to the presence of recipient antibodies, future compatibility may be affected.
- Febrile nonhemolytic reactions are due to recipient antibodies to donor white blood cells, and occurs in about 7% of transfusions. This may occur after exposure from previous transfusions. Fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. This is a reason for the now-widespread use of leukoreduction - the filtration of donor white cells from red cell product units.
- Allergic reactions may occur when the recipient has preformed antibodies to certain chemicals in the donor blood, and does not require prior exposure to transfusions. Symptoms include urticaria, pruritus, and may proceed to anaphylactic shock. Treatment is the same as for any other type 1 hypersensitivity reactions. A small population (0.13%) of patients are deficient in the immunoglobin IgA, and upon exposure to IgA-containing blood, may develop an anaphylactic reaction.
- Posttransfusion purpura is a rare complication that occurs after transfusion containing platelets that express a surface protein HPA-1a. Recipients who lack this protein develop sensitization to this protein from prior transfusions, and develop thrombocytopenia about 7–10 days after subsequent transfusions. Treatment is with intravenous immunoglobulin, and recipients should only receive future transfusions with washed cells or HPA-1a negative cells.
- Transfusion-associated acute lung injury (TRALI) is an increasingly recognized adverse event associated with blood transfusion. TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension, which may occur as often as 1 in 2000 transfusions. Symptoms can range from mild to life-threatening, but most patients recover fully within 96 hours, and the mortality rate from this condition is less than 10%. Although the cause of TRALI is not clear, it has been consistently associated with anti-HLA antibodies. Because these types of antibodies are commonly formed during pregnancy, several transfusion organisations have decided to use only plasma from men for transfusion. TRALI is typically associated with plasma components rather than packed red blood cells (RBCs), though there is some residual plasma in RBC units.
Infectious
- Rarely, blood products are contaminated with bacteria. This can result in life-threatening infection, also known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions. It is important to note that blood product contamination, while rare, is still more common than actual infection. The reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. Contamination is also more common with longer duration of storage, especially when exceeding 5 days. Sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and from containers. Contaminating organisms vary greatly, and include skin flora, gut flora, or environmental organisms. There are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination. A definite diagnosis of transfusion-transmitted bacterial infection includes the identification of a positive culture in the recipient (without an alternative diagnosis) as well as the identification of the same organism in the donor blood.
- Since the advent of HIV testing of donor blood in the 1980s the transmission of HIV during transfusion has dropped dramatically. Prior testing of donor blood only included testing for antibodies to HIV. However, due to latent infection (the "window period" in which an individual is infectious, but has not had time to develop antibodies), many cases of HIV seropositive blood were missed. The development of a nucleic acid test for the HIV-1 RNA has dramatically lowered the rate of donor blood seropositivity to about 1 in 3 million units. As transmittance of HIV does not necessarily mean HIV infection, the latter could still occur, at an even lower rate.
- The transmission of hepatitis C via transfusion currently stands at a rate of about 1 in 2 million units. As with HIV, this low rate has been attributed to the ability to screen for both antibodies as well as viral RNA nucleic acid testing in donor blood.
- Other rare transmissible infections include hepatitis B, syphilis, Chagas disease, cytomegalovirus infections (in immunocompromised recipients), HTLV, and Babesia.
Procedures
Massive transfusion protocol
A massive transfusion protocol is typically defined as when it is anticipated that more than ten units of packed red blood cells will be needed.Typically higher ratios of fresh frozen plasma
and platlets are given relative to pakes red blood cells.
Adverse effects
Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is also increasing focus (and controversy) on complications arising directly or indirectly from potential quality degradation during storage.Overall, adverse events from transfusions in the US account for about $17Billion - and in effect add more to the cost of each transfusion than acquisition and procedure costs combined.While some complication risks depend on patient status or specific transfusion quantity involved, a baseline risk of complications simply increases in direct proportion to the frequency and volume of transfusion.
Immunologic
- Acute hemolytic reactions occur with transfusion of red blood cells, and occurs in about 0.016 percent of transfusions, with about 0.003 percent being fatal. This is due to destruction of donor erythrocytes by preformed recipient antibodies. Most often this occurs due to clerical errors or improper typing and crossmatching. Symptoms include fever, chills, chest pain, back pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop in blood pressure. When suspected, transfusion should be stopped immediately, and blood sent for tests to evaluate for presence of hemolysis. Treatment is supportive. Kidney injury may occur due to the effects of the hemolytic reaction (pigment nephropathy).
- Delayed hemolytic reactions occur more frequently (about 0.025 percent of transfusions) and are due to the same mechanism as in acute hemolytic reactions. However, the consequences are generally mild and a great proportion of patients may not have symptoms. However, evidence of hemolysis and falling hemoglobin levels may still occur. Treatment is generally not needed, but due to the presence of recipient antibodies, future compatibility may be affected.
- Febrile nonhemolytic reactions are due to recipient antibodies to donor white blood cells, and occurs in about 7% of transfusions. This may occur after exposure from previous transfusions. Fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. This is a reason for the now-widespread use of leukoreduction - the filtration of donor white cells from red cell product units.
- Allergic reactions may occur when the recipient has preformed antibodies to certain chemicals in the donor blood, and does not require prior exposure to transfusions. Symptoms include urticaria, pruritus, and may proceed to anaphylactic shock. Treatment is the same as for any other type 1 hypersensitivity reactions. A small population (0.13%) of patients are deficient in the immunoglobin IgA, and upon exposure to IgA-containing blood, may develop an anaphylactic reaction.
- Posttransfusion purpura is a rare complication that occurs after transfusion containing platelets that express a surface protein HPA-1a. Recipients who lack this protein develop sensitization to this protein from prior transfusions, and develop thrombocytopenia about 7–10 days after subsequent transfusions. Treatment is with intravenous immunoglobulin, and recipients should only receive future transfusions with washed cells or HPA-1a negative cells.
- Transfusion-associated acute lung injury (TRALI) is an increasingly recognized adverse event associated with blood transfusion. TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension, which may occur as often as 1 in 2000 transfusions. Symptoms can range from mild to life-threatening, but most patients recover fully within 96 hours, and the mortality rate from this condition is less than 10%. Although the cause of TRALI is not clear, it has been consistently associated with anti-HLA antibodies. Because these types of antibodies are commonly formed during pregnancy, several transfusion organisations have decided to use only plasma from men for transfusion. TRALI is typically associated with plasma components rather than packed red blood cells (RBCs), though there is some residual plasma in RBC units.
Infectious
- Rarely, blood products are contaminated with bacteria. This can result in life-threatening infection, also known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions. It is important to note that blood product contamination, while rare, is still more common than actual infection. The reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. Contamination is also more common with longer duration of storage, especially when exceeding 5 days. Sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and from containers. Contaminating organisms vary greatly, and include skin flora, gut flora, or environmental organisms. There are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination. A definite diagnosis of transfusion-transmitted bacterial infection includes the identification of a positive culture in the recipient (without an alternative diagnosis) as well as the identification of the same organism in the donor blood.
- Since the advent of HIV testing of donor blood in the 1980s the transmission of HIV during transfusion has dropped dramatically. Prior testing of donor blood only included testing for antibodies to HIV. However, due to latent infection (the "window period" in which an individual is infectious, but has not had time to develop antibodies), many cases of HIV seropositive blood were missed. The development of a nucleic acid test for the HIV-1 RNA has dramatically lowered the rate of donor blood seropositivity to about 1 in 3 million units. As transmittance of HIV does not necessarily mean HIV infection, the latter could still occur, at an even lower rate.
- The transmission of hepatitis C via transfusion currently stands at a rate of about 1 in 2 million units. As with HIV, this low rate has been attributed to the ability to screen for both antibodies as well as viral RNA nucleic acid testing in donor blood.
- Other rare transmissible infections include hepatitis B, syphilis, Chagas disease, cytomegalovirus infections (in immunocompromised recipients), HTLV, and Babesia.
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