Transfusion Medicine

At the blood manufacturing site, certain tests must be performed on all donated blood. In addition to typing blood to determine the donor's ABO blood group and D 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
• Hepatitis E
• HIV types 1 and 2
• Syphilis

The first blood donation and some subsequent donations are tested for:

• Human T-Lymphotropic Virus (HTLV) types I and II (a serious but relatively rare illness)

The following tests are not performed on each and every donation but tested after assessing the donor’s circumstances (such as travel history):

• West Nile Virus
• Trypanosoma cruzi (T-cruzi)
• Malaria

Testing for the infectious diseases in the bulleted list above often is done by antibody screening. However, newer tests for viruses are 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.

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.

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

• Red blood cells must be refrigerated and can be kept for a maximum of 35 days.
• Platelets can be stored at room temperature for 5 -7 days.
• Fresh frozen plasma and cryoprecipitate can be kept frozen for 36 months.
• 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 the RhD antigen. If it is present on your red blood cells, your blood is D+ (positive); if it is absent, your blood is D- (negative).

According to NHSBT, the distribution of blood types in the UK is as follows:

• O positive: 35%
• A positive: 30%
• O negative: 13%
• A negative: 8%
• B positive: 8%
• B negative: 2%
• AB positive: 2%
• AB negative: 1%

ABO and D 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 D typing a sample of a person's red blood cells is mixed with an anti-serum containing anti-D antibodies. If agglutination occurs, then the blood is D-positive; if no reaction is observed, then the blood is D-negative. D testing is especially important during pregnancy because a mother and her foetus could be incompatible. If the mother is D-negative but the father is D-positive, the foetus may be positive for the D antigens. As a result, the mother's body could develop antibodies against D, which can destroy the baby's red blood cells. To prevent development of D antibodies, an D-negative mother is treated with an injection of anti-D immunoglobulin during the pregnancy and again after delivery if the baby is D-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 and D blood typing (see above), antibody screening (for unexpected red blood cell antibodies that could cause problem in the recipient), and crossmatching.

There are many antigens besides A, B, and D. Some groups of patients, such as those with sickle cell anaemia and thalassaemia, require a more extended match of antigens to prevent antibody formation.

If a patient has had a previous transfusion or has 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.

Crossmatching 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, in an emergency, such as major haemorrhage, O D-negative red blood cells may be used. Therefore, people with type O blood (particularly O D-negative) are called "universal donors." People with type AB D-positive blood can be transfused with red blood cells from individuals of any ABO type and are commonly referred to as "universal recipients."

Donation of blood is safe to do however occasionally complications do occur such a fainting after donation, bruising to the area or rarely, nerve damage. In the UK, there was approximately 1.9 million donations made in the UK in 2017 and only 50 serious adverse events were reported. A new, sterile needle is used for each donation procedure and therefore, you cannot get infected with viruses, such as HIV or hepatitis by donating blood.

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.

There are some risks with receiving a transfusion of blood or a blood component. Some people fear that they may contract a transfusion transmitted infection (TTI) 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 (greater than 1 in 1 million units transfused for hepatitis B, greater than 1 in 5 million units transfused for HIV and greater than 1 in 50 million units for 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 donor blood cells that can be very dangerous, even life-threatening. Besides 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 may attack and remove the donated blood cells, with potential side effects for the patient.

There are several types of transfusions reactions. 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 paracetamol may be prescribed to reduce fever). Many transfusion reactions go undetected and, therefore, unreported. The majority of complications relating to transfusion are non-infectious and include receiving the incorrect blood component, haemolytic transfusion reactions, transfusion associated circulatory overload (TACO), 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, 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 and immunoglobulins.

Red blood cells (RBCs) typically make up about 40% of the blood volume. RBCs contain haemoglobin, a protein that binds to oxygen and enables RBCs to carry oxygen from the lungs to the tissues and organs of the body. Packed RBCs are prepared from whole blood by removing the plasma and platelets from the collection bag. They may be transfused in the treatment of anaemia resulting for example, after chemotherapy or for 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. For those born on or after 1st January 1996, non-UK sourced plasma which has undergone a viral inactivation method (such as solvent detergent or methylene blue treated) is indicated. This precaution was introduced to prevent transmission of variant Creutzfeldt-Jakob disease (CJD) from plasma components in the UK.

Fresh frozen plasma (FFP) is prepared from whole blood and frozen at <-25 °C. Donor FFP must be compatible with the recipient's red blood cells. Plasma is indicated in management of conditions such as:

• Major Haemorrhage
• Management of patients with single coagulation factor deficiencies for which no specific coagulation concentrates are available (use a virally inactivated form whenever possible)
• For transfusion or plasma exchange in patients with low or non-functioning platelets, thrombotic thrombocytopenic purpura (TTP). Note: solvent detergent-treated plasma is indicated for plasma exchange in TTP.

FFP is not indicated for the reversal of warfarin, for vitamin K deficiency or as fluid replacement.

Cryoprecipitate is a fraction of FFP prepared by a process of rapid freezing and slow thawing. Cryoprecipitate is rich in fibrinogen and also contains von Willebrand factor (vWF), Factor VIII, Factor XIII and fibronectin. It is indicated for the replacement of fibrinogen to prevent or aid control of bleeding.

A non-UK sourced, methylene blue (MB) treated form of cryoprecipitate is available in the UK for use for patients who are born on 1st January 1996 or after.

Platelets are tiny fragments of cells that are essential for normal blood clotting. Platelets may be used in conditions which patients have a shortage of platelets (e.g., thrombocytopaenia) such as during the treatment of leukaemia and other types of cancer, or for patients who have abnormal platelet function.

Each dose of platelets is pooled from platelet concentrates, derived from whole blood, and suspended in a small amount of 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. Platelets are essential for normal haemostasis. Platelet transfusions are indicated to prevent or control bleeding due to critically decreased circulating platelet count or for patients with functionally abnormal platelets.