Transfusion Medicine

Blood donors are volunteers who provide a greatly needed service. About 4 million patients receive blood transfusions each year, and approximately 40,000 units of red blood cells are needed every day. Although 14 million blood units are donated a year, more volunteers are needed to keep the blood supply at an adequate volume. According to AABB, although an estimated 38% of the U.S. population is eligible to donate blood at any given time, less than 10% actually do so annually.

Who can donate blood? 
Donors must meet certain criteria to ensure their safety and the safety of the recipients. Rules of eligibility have been established by the U.S. Food and Drug Administration (FDA), although some donor centers may have additional requirements.

Donors must:

• Be at least 17 years of age (although some states permit younger people to donate if they have parental consent)
• Be in good health
• Weigh at least 110 pounds (Some facilities will allow people who weigh less to donate, but they must then adjust the amount of blood collected and the amount of anticoagulant in the collection bags.)
• Pass a physical and health history examination prior to donation

The physical includes measurement of blood pressure, pulse, and temperature as well as a test for anemia, which requires just a few drops of blood from your finger.

To protect the health of both the donor and the recipient, the health history questionnaire asks about potential exposure to transfusion-transmissible diseases, such as viruses like HIV, hepatitis B and C, and HTLV I and II as well as parasites that cause malaria, babesiosis, and Chagas disease.

Certain people are not permitted to donate blood for health concerns. This includes:

• Anyone who has ever used illegal intravenous (IV) drugs
• Men who have had sexual contact with other men since 1977; in May 2015, the FDA developed a draft guidance that may be finalized by the end of the year. If finalized, it would change this restriction to men who have had sexual contact with men in the last 12 months.
• Hemophiliacs
• Anyone with a positive test for HIV
• Men and women who have ever taken money, drugs, or other payment for sex since 1977
• Anyone who has had hepatitis since his or her eleventh birthday
• Anyone who has had babesiosis or Chagas disease
• Anyone with Crueutzfeldt-Jakob disease (CJD) or who has an immediate family member with CJD
• Because of CJD, anyone who has spent time in the United Kingdom between 1980-1996 that adds up to 3 months or more; anyone who, from 1980 to the present, spent time in Europe that adds up to 5 years or more; and anyone who received a blood transfusion in the UK between 1980 and the present.
• Some travel or health problems may require a temporary deferral.

There also may be some restrictions if you are taking certain medications at the time of donation. You may be ineligible to donate or deferred for a period of time. For example, the FDA has specified that individuals on Tegison (etretinate), human growth hormone, or bovine insulin from the United Kingdom must be deferred indefinitely. Those taking Proscar (finasteride), Propecia (finasteride), or Accutane (isotretinoin) will be deferred from donating for 4 weeks following last dose. Use of hepatitis B immune globulin results in a 12-month deferral and Soriatane (acitretin) is a 3-year deferral. In addition, if you are taking an antibiotic or any other medication for an infection, you will be evaluated and deferred temporarily. There also are varying deferral periods if you have been vaccinated recently. For a more complete list, review “Medications” in the American Red Cross’s blood donation eligibility criteria.

Donors have a personal responsibility to help ensure the safety of the blood supply. You should express any concerns or questions you may have about past illnesses you had or may have been exposed to before donating.

Where can blood be donated? 
Blood can be donated at community blood centers, hospital-based donor centers, or mobile sites temporarily set up in public areas like colleges, workplaces, and churches. There are hundreds of institutions involved in blood banking throughout the U.S.

For more information on where you can go to donate, visit AABB’s online Locator.

What is donated and how often? 
Usually one unit (about a pint) of blood is collected into a blood bag from a vein in the inner part of the elbow joint using a new, sterile needle. Your body replenishes the fluid lost during donation in 24 hours, but it may take up to 2 months to replace the lost red blood cells. Therefore, whole blood can be donated only once every 8 weeks. Two units of red blood cells can be donated at a time, using a process called red cell apheresis, every 16 weeks. Platelets can also be donated by apheresis, usually every 4 weeks.

What is autologous blood donation?
Another type of blood donation is autologous donation. This refers to transfusions in which the blood donor and the transfusion recipient are the same. People may elect to do this before a surgical procedure in which the likelihood of needing a transfusion is high. Although there are still risks with this process, autologous donation minimizes many of them because it is the person’s own blood that is being returned to his or her body.

A person can donate their blood up until 72 hours prior to their surgery. Iron supplements or erythropoietin also may be prescribed to help increase the person’s red blood cell count. Any blood that remains unused during the surgery is usually discarded. However, the blood can be transfused into another patient if it has been fully tested and is compatible with the recipient.

According to the National Blood Collection and Utilization Survey and AABB, autologous blood accounted for 0.7% of all donated blood in 2011. The use of this type of donation varies by location, and not all physicians recommend it. There has been some concern about low hematocrit levels following surgery in patients who donate autologous units. The decision should be made together by the patient and his or her doctor. Other options may be preferred, such as intra-operative blood salvage, in which any blood lost during the surgery can be collected and returned to the patient.

What happens to blood after it is donated?
When a unit of whole blood is donated, the components can be separated in the laboratory so that they can be transfused into multiple patients, each with different needs. Rarely will a person need all of the components that comprise whole blood.

In the blood bank laboratory, certain tests must be performed on all donated blood. In addition to typing blood to determine the donor’s ABO blood group and Rh status, several screens are performed to ensure the safety of the blood. Screening is conducted for:

1. Unexpected red blood cell antibodies that could cause reactions in the recipient, such as those made as a result of a previous transfusion or pregnancy
2. Bacterial contamination in units of platelets
3. Current and past transmissible infections; each unit of donated blood is tested for:

• • Hepatitis B
  • Hepatitis C
  • HIV types 1 and 2
  • Human T-Lymphotropic Virus (HTLV) types I and II (a serious but relatively rare illness in the U.S.)
  • Syphilis
  • West Nile Virus

Additionally, the U.S. Food and Drug Administration (FDA) has directed blood collection facilities to screen all donated blood and blood components for the Zika virus. The FDA approved two investigational tests for this purpose. The tests were approved under an “investigational new device (IND)” protocol and did not go through the standard regulatory process prior to implementation, which can be time-consuming. The tests screen for the presence of the virus by detecting its genetic material (RNA). Units of blood that test positive for the virus are removed from the supply and not used for transfusions.

The FDA has also approved a test to detect blood infected with Chagas disease. The test is not yet mandatory, but many facilities have already begun screening all blood donors for this disease.

Testing for the infectious diseases in the bulleted list above often is done by antibody screening. However, newer tests for virusesare available that detect the genetic material of the viruses, which shortens the window of time in which the virus may be undetectable in a donor. Known as nucleic acid amplification testing (NAT), this methodology is being used routinely to screen donated blood for hepatitis and HIV and has helped improve the safety of the blood supply in this country.

Confirmatory tests are performed in duplicate if any test results are positive in order to rule out false positives. If both confirmatory test results are negative, the initial screening result may be considered a false positive. Depending on the facility and the guidelines used, the unit may then be released for use. Some facilities discard the unit regardless of the confirmatory test result.

Once the testing is completed, those units of blood that are free of infection are made available for transfusion when needed. Those in which infection is detected are discarded, and the donor is notified as well as prohibited from future blood donation.

It also is important to realize that there are some infectious diseases that are not or cannot be tested for at the present time, such as malaria. The potential for an infectious agent that will not be detected by testing to be present in a donated unit underscores the importance of donors reporting any transmissible infections they have had or may have been exposed to in the past.

Storing Blood Safely 
Proper storage of whole blood and blood components is essential.

• Red blood cells must be stored under refrigeration and can be kept for a maximum of 42 days or frozen for up to 10 years.
• Platelets can be stored at room temperature for a maximum of 5 days.
• Fresh frozen plasma can be kept frozen for up to 1 year.
• Cryoprecipitate AHF made from fresh frozen plasma can be stored frozen for up to 1 year.
• Granulocytes (white blood cells) must be transfused within 24 hours of donation.

Blood Typing 
Blood typing involves testing a person’s blood for the presence or absence of certain antigens that are present on the red blood cells. Two of these antigens, or surface identifiers, are the A and B markers included in ABO typing. People whose red blood cells have A antigens are considered to be blood type A; those with B antigens are type B; those with both A and B antigens are type AB; and those who do not have either of these makers are considered to have blood type O. Our bodies produce antibodies against those ABO antigens we do not have on our red blood cells, which is why we can receive blood only from donors with certain blood types.

Another important surface antigen is called Rh factor. If it is present on your red blood cells, your blood is Rh+ (positive); if it is absent, your blood is Rh- (negative).

According to AABB, the distribution of blood types in the U.S. is as follows:

• O Rh-positive 38%
• A Rh-positive 34%
• B Rh-positive 9%
• O Rh-negative 7%
• A Rh-negative 6%
• AB Rh-positive 3%
• B Rh-negative 2%
• AB Rh-negative 1%

ABO and Rh blood typing are conducted on all donor units by the collection facility and in the laboratory for hospital patients. There are two steps to ABO typing: forward and reverse typing. First, forward typing is performed by mixing a sample of blood with anti-A serum (serum that contains antibodies against type A blood) and with anti-B serum (serum that contains antibodies against type B blood). Whether the blood cells stick together (agglutinate) in the presence of either of these sera determines the blood type. Second, in reverse typing, the patient’s serum is mixed with blood that is known to be either type A or B to watch for agglutination. A person’s blood type is confirmed by the agreement of these two tests.

Similarly, with Rh typing a sample of a person’s red blood cells is mixed with an anti-serum containing anti-Rh antibodies. If agglutination occurs, then the blood is Rh-positive; if no reaction is observed, then the blood is Rh-negative. Rh testing is especially important during pregnancy because a mother and her fetus could be incompatible. If the mother is Rh-negative but the father is Rh-positive, the fetus may be positive for the Rh antigens. As a result, the mother’s body could develop antibodies against Rh, which can destroy the baby’s red blood cells. To prevent development of Rh antibodies, an Rh-negative mother with an Rh-positive partner is treated with an injection of Rh immunoglobulin during the pregnancy and again after delivery if the baby is Rh-positive.

Compatibility Testing 
Compatibility testing is performed to determine if a particular unit of blood can be transfused safely into a certain patient. This includes ABO-Rh blood typing (see above), antibody screening (for unexpected red blood cell antibodies that could cause problem in the recipient), and cross-matching.

There are many antigens besides A, B, and Rh. However, neither the donor nor the recipient is tested routinely for these other antigens. However, if a patient has had a previous transfusion or been pregnant, they may have developed antibodies to one of these other antigens. Therefore, it will be important in all future transfusions that the donor’s red blood cells do not have that particular antigen; otherwise, the recipient may have a transfusion reaction. The presence of such an antibody is determined by doing an antibody screening test by mixing the patient’s serum with red cells of a known antigenic makeup.

Cross-matching is performed to determine if the patient has antibodies that react with the donor’s cells. If there is a reaction, the laboratory staff will investigate further to identify the specific antibody and locate donor units that lack the antigen that matches the patient’s antibody. This unit will then be tested to confirm that this is a safe match.

It is ideal to receive a blood transfusion with blood that matches your blood type exactly. However, anyone can receive type O red blood cells in an emergency. Therefore, people with type O blood (particularly O Rh-negative) are called “universal donors.” People with type AB Rh-positive blood can be transfused with red blood cells from individuals of any ABO type and are commonly referred to as “universal recipients.”

Are there risks associated with donating or receiving blood? The blood banking community assures the U.S. public that it is safe to donate blood. A new, sterile needle is used for each donation procedure. Therefore, you cannot get infected with viruses, such as HIV or hepatitis, by donating blood.

In addition, donors are screened before giving blood to ensure that they are in good health and have no complications that could cause them harm by donating. Mild side effects from the procedure that a donor might experience include stinging during insertion of the needle, upset stomach, dizziness, and possibly a small amount of bruising later at the site of the blood draw. In very rare cases, a donor may faint, have muscle spasms, or suffer nerve damage.

There are some risks with receiving blood transfusions. Some people fear that they may contract an infectious disease. However, donated blood is carefully screened for transmittable diseases, as noted earlier in this article. The risk of infection from transfusion is now extremely low (about 1 in 600,000 units transfused for hepatitis B and about 1 in 2 million units transfused for HIV and hepatitis C). Of greater concern is ABO incompatibility and transfusion reactions.

ABO incompatibility occurs when a unit of blood is transfused and the recipient has antibodies to the ABO antigens on the donor unit red cells (for example, a group O recipient receives a group A unit of red cells). The recipient of the blood transfusion could have an immune reaction against the foreign blood cells that can be very dangerous, even life-threatening. Besides just ABO incompatibility, there are other incompatibilities that can cause transfusion reactions. Antigens occur on other blood components, including white blood cells, platelets, and plasma proteins. The immune system will attack and destroy the donated blood cells, with serious side effects for the patient.

There are several types of transfusions reactions, such as allergic and febrile (characterized by fever). Treatment will depend on the type of reaction and the patient’s symptoms (for example, antihistamines may be used to reduce rash and itching from allergic reactions while acetaminophen may be prescribed to reduce fever). Many transfusion reactions go undetected and, therefore, unreported. However, the reported rate of transfusion reactions is on the order of 1 per 1,000 components or 1 in 400 people. Nearly all of these are non-infectious complications and include mis-transfusion, volume overload, febrile or allergic reactions, and transfusion-related acute lung injury (TRALI), a serious but infrequent reaction where the patient can develop breathing problems and may have a high fever.

Blood is made up of a few different types of cells suspended in fluid called plasma, which contains proteins like clotting factors and other substances. The blood that flows through the body in veins and arteries is called whole blood. Each of the components of whole blood has an important role.

Separation of these components is performed by first treating the blood to prevent clotting and then letting the blood stand. Red blood cells settle to the bottom, while plasma migrates to the top. Using a centrifuge to spin out these components can speed up the process. The plasma is then removed and placed in a sterile bag. It can be used to prepare platelets, plasma, and cryoprecipitate antihemophilic factors, again with the help of a centrifuge to separate out the platelets. Plasma may be pooled with that from other donors and processed further (fractionated) to provide purified plasma proteins, such as albumin, immunoglobulin, and clotting factor concentrates.

Whole blood contains red blood cells for transport of oxygen to tissues, white blood cells for fighting infection, platelets for clotting, and plasma, the fluid part of whole blood. Compatibility testing is required before transfusion of whole blood.

Red blood cells (RBCs) typically make up about 40% of the blood volume. RBCs contain hemoglobin, a protein that binds to oxygen and enables RBCs to carry oxygen from the lungs to the tissues and organs of the body. RBCs are prepared from whole blood by removing the plasma from the collection bag. They may be transfused in the treatment of anemia resulting from, for example, kidney failure, gastrointestinal bleeding, or blood loss during trauma or surgery. Donor red blood cells must be compatible with the recipient’s plasma. Compatibility testing is required before transfusion.

Plasma is the fluid portion of blood. It consists of water, fats, sugar, protein and salts. Its main functions are to transport the blood cells throughout the body as well as other substances, such as nutrients, clotting factors, antibodies, and waste products. It helps to maintain blood pressure and the fluid-electrolyte and acid-base balances of the body. Plasma may be transfused to help control bleeding when no coagulation factor-specific concentrate is available.

Fresh frozen plasma (FFP) is prepared from whole blood or apheresis collection and frozen at -18C. Donor FFP must be compatible with the recipient’s red blood cells. FFP serves as a source of plasma proteins for patients who are deficient in or have defective plasma proteins. FFP use is indicated in management of:

• Preoperative or bleeding patients who require replacement of multiple plasma coagulation factors
• Patients with massive transfusion who have clinically significant coagulation deficiencies
• Patients on warfarin (an anticoagulant) who are bleeding
• For transfusion or plasma exchange in patients with low or non-functioning platelets (thrombotic thrombocytopenic purpura)
• Management of patients with selected coagulation factor deficiencies for which no specific coagulation concentrates are available
• Management of patients with rare specific plasma protein deficiencies

Plasma, cryoprecipitate reduced is prepared from FFP by a process of rapid freezing, followed by thawing and centrifugation, which removes the cryoprecipitate and yields plasma that is deficient in Factor VIII, von Willebrand factor (vWF), and fibrinogen. Other plasma proteins remain in the same concentration as in FFP and, like FFP, this component must be compatible with the recipient’s red blood cells.

Cryoprecipitate antihemophilic factors (AHF) are part of the plasma that contains clotting factors to help control bleeding in people with hemophilia and von Willebrand’s disease. It is only used in most places in the U.S. when viral-inactivated concentrates containing Factor VIII and von Willebrand factor are unavailable or, at times, during surgery as a hemostatic preparation (fibrin sealant).

Cryoprecipitated AHF is prepared by thawing FFP and recovering the precipitate. Cryoprecipitated AHF contains coagulation Factor VIII, Factor XIII, fibrinogen, vWF, and fibronectin. Transfusion of cryoprecipitated AHF does not require compatibility testing; all ABO groups are acceptable.

Platelets are tiny fragments of cells that are essential for normal blood clotting. Platelets may be used in the treatment of leukemia and other types of cancer and conditions in which patients have a shortage of platelets (e.g., thrombocytopenia) or abnormal platelet function to control bleeding.

A unit of platelets is a concentrate of platelets separated from a unit of Whole Blood and suspended in a small amount of the original plasma. Platelets may also be collected by apheresis specific for platelets (plateletpheresis). It is preferred that donor platelets be compatible with the recipient’s red blood cells though compatibility testing is not required. All ABO groups are acceptable for transfusion. Platelets are essential for normal hemostasis. Platelet transfusion is indicated for treatment of patients bleeding due to critically decreased circulating platelet count or functionally abnormal platelets.

White blood cells (WBCs) are an important part of the body’s defense system. They help protect against infections and also have a role in inflammation, allergic responses, and protecting against cancer. One type, called granulocytes, can be transfused to fight infections that are unresponsive to antibiotic therapy, although the effectiveness of this form of treatment is still being investigated.

Factor VIII preparations can be derived from human plasma or produced by recombinant technology. Recombinant Factor VIII is the product of choice for treating hemophilia A because it is derived from hamster cell lines and thought to be very safe in regard to transmitting human infectious organisms. Human plasma-derived Factor VIII concentrate (anti-hemophilic factor, AHF) is prepared by fractionation of pooled human plasma that is frozen soon after phlebotomy. Factor VIII concentrate is indicated for treatment or prevention of bleeding episodes in hemophilia A patients with moderate-to severe congenital Factor VIII deficiency.

• Recombinant and plasma-derived Factor IX concentrates are available.
• Recombinant Factor IX is the treatment of choice for new patients with hemophilia B.
• Factor IX concentrates are used for the treatment of patients with Factor IX deficiency, commonly known as hemophilia B.

• Albumin is derived from donor plasma obtained from whole blood donation or plasmapheresis (apheresis specific for plasma). It is composed of 96% albumin, 4% globulin and other proteins and is prepared by a cold fractionation process. These products do not transmit viral diseases.
• Plasma Protein Fraction (PPF) is a similar product that contains 83% albumin and 17% globulin.
• Albumin is used in patients whose volume of blood is dangerously low (hypovolemic) and who have low concentrations of proteins in their blood (hypoproteinemic). Indications for PPF are the same.

Immune globulins are preparations of antibodies that protect against certain diseases and are derived from pools of human plasma.

• Gammaglobulin preparations and specific hyperimmune globulin preparations with high titers against specific infectious agents or toxins are available for intramuscular use (IMIG). Intramuscular products are given primarily for disease protection or prophylaxis.
• Intravenous gammaglobulin (IVIG) preparations provide a mechanism to achieve peak levels of IgG immediately after infusion.
• Immune globulin preparations can be used to provide passive antibody prophylaxis for susceptible individuals exposed to certain diseases and a replacement therapy in primary immunodeficiency states.

Synthetic volume expanders are solutions that are manufactured and are not derived from human blood. When patients do not need the benefits of blood transfusion, such as the oxygen-carrying capacity from red blood cells, but need the volume of their body fluids increased, these solutions may be given intravenously.

• Solutions such as normal saline and Ringer’s Lactate are compatible with plasma. Normal saline contains only sodium and chloride ions, while Ringer’s lactate also contains potassium, calcium and lactate. Solutions such as normal saline and Ringer’s Lactate alone expand the plasma volume temporarily as they rapidly cross capillary membranes.
• Solutions used for volume expansion include Dextran and hydroxyethyl starch (HES). Both Dextran and HES are useful as volume expanders in hemorrhagic shock (shock resulting from extreme blood loss) and the treatment of burns.

Leuko-reduced blood products

This type of component is prepared by removing all or most of the white blood cells (WBCs, leukocytes) from the component. The use of leuko-reduced blood products (red blood cells, platelets) is indicated for patients who have repeated febrile (fever) transfusion reactions. The use of these components has also been shown to reduce the formation of HLA antibodies (antibodies directed against human leukocyte antigens, markers found on WBCs). It also reduces the risk of transfusion-transmissable CMV (cytomegalovirus).

Irradiated blood products

These are blood components that have been exposed to gamma rays or X-rays. This process prevents transfusion-related graft versus host disease (TA-GVHD), a condition in which the white blood cells from the donor produce an immune response against (attack) recipient’s cells. Irradiation prevents donor white blood cells from replicating in the recipient and prevents complications from TA-GVHD. Irradiated blood products are indicated for use in patients with compromised immune systems.