Transfusion medicine comprises of blood and blood component transfusion. Blood cannot be synthesized artificially. So, the source of blood is from a healthy human donor.

BLOOD TRANSFUSION

Blood transfusion is the process of transferring blood/blood products from donor into the circulating system of recipient. It is important to properly collect the blood from donor, prepare its components (if required) and store blood/components in a proper way and transfuse in such a way to avoid any risks or hazards.

Types of Blood Donations

•• Whole blood donation: In this one unit (350 mL) of whole blood is collected in an anticoagulant.

•• Autologous donation: In this type blood is collected for an individual for subsequent transfusion to the same individual from whom the blood is collected.

•• Apheresis donation: In this whole blood is removed from donor and is separated. Only desired portion is retained and the remaining portion is returned to the donor.

Sequential Steps in Blood Transfusion

Donor Selection

Donor selection is based on medical history and few routine physical examinations (weight, blood pressure, temperature, hemoglobin) are done to know whether donor is suitable for donating blood.

•• Donor should be healthy and free from diseases of heart, lung, liver and kidney. Donor also should not suffer from cancer, diabetes, epilepsy, tuberculosis, bleeding disorder, allergy, malaria, sexually transmitted disease. There are three types of donors namely voluntary(donates blood out of individuals own free will should be encouraged), replacement(replaces the unit of blood used for the patient) and professional (for money).

•• It is important to know whether the patient has history of diseases like hepatitis, AIDS, syphilis and if so, blood should not be obtained from them. In the blood bank, blood is routinely screened for few common infections.

Collection of Blood

•• Blood is collected by phlebotomy under aseptic conditions using sterile, plastic bag with anticoagulant (Fig. 60.1).

Fig. 60.1: Triple plastic bag for blood collection

Now CPD-A is used as an anticoagulant.

•• Mix the blood and anticoagulant gently and periodically during its collection.

Anticoagulants used: 

The different anticoagulants—preservative solutions available are:

•• Citrate phosphate dextrose (CPD).

•• Citrate phosphate dextrose adenine (CPDA-1). Functions of various chemicals used in CPDA-1 are mentioned in Table 60.1.

•• Acid citrate dextrose (ACD) is not used nowadays.

Storage of blood:

Blood is stored in a refrigerator at 2° to 6°C.

Predonation Check-up

Donor blood: The following tests are routinely carried out on donor’s blood.

•• ABO and Rh grouping.

•• Screening tests for infections transmissible by transfusion:

–– HBsAg, anti-HCV, anti HIV-1 and HIV-2 and serum alanine aminotransferase (ALT)

–– Malaria and syphilis.

Recipient blood: The recipient’s ABO and Rh grouping is also carried out.

Compatibility Testing (Pretransfusion Testing)

Before transfusion of any blood or its components, it is essential to know whether they are compatible with the recipient’s blood. This is achieved by performing a set of procedures known as compatibility testing. Sometimes the term compatibility test and cross matching are used interchangeably, but cross-match is only a part of compatibility test. The aim of compatibility testing is to prevent the transfusion of incompatible blood unit and thereby prevent hemolytic transfusion reactions in the recipient.

Compatibility tests include:

•• Review of patient’s past blood bank history and records (if done earlier).

•• ABO and Rh typing of the recipient and donor.

•• Antibody screening test of recipient’s and donor’s serum.

•• Cross-matching. There is no need of cross-matching for transfusion of platelets or fresh frozen plasma. However, fresh frozen, cross-matching is not.

Cross-matching (Tables 60.3 and 60.4)

Cross-matching is very important before any blood transfusion. Cross-matching should be carried out to ensure that there are no antibodies in patient’s serum that will react with the donor’s cells when transfused.

 Importance of cross-matching

•• It is the final check of ABO compatibility between donor and recipient.

•• Detects the presence of any clinically significant, unexpected antibodies in the recipient’s serum that may react with donor’s cells, thereby preventing any transfusion reaction. A thorough cross-matching is performed with recipient’s serum and donor’s red cells.

Types 

Cross-matching procedure may be divided into two major parts, namely major and minor cross-matching. Major cross-matching consists of mixing donor’s red cells with recipient’s(patient’s) serum; whereas minor cross-matching consists of mixing patient’s red cells with donor’s serum (Table 60.3).

Major cross-matching (immediate spin cross-match): The simplest method is:

•• Place one drop of patient’s serum in a prelabeled glass test tube.

•• Add one drop of 5% saline suspension of donor’s red cells to the above test tube.

•• Mix them and incubate at 37°C for 30 minutes. Centrifuge at 1,000 rpm for 1 minute.

•• Examine the tube for agglutination or hemolysis.

Interpretation

•• If there is no agglutination or hemolysis it indicates compatibility.

•• Agglutination or hemolysis indicates mismatching and recipient should not be transfused with the tested donor blood/component.

Minor cross-matching: The above procedure may also be carried out by taking one drop of donor’s serum and one drop of 5% saline suspension of recipient’s red cells. Incubate at 37°C for 30 minutes. Centrifuge at 3,000 rpm for 1 minute. Observe for agglutination or hemolysis. It is always necessary to monitor the recipient during and after transfusion so that any complications can be dealt accordingly.

Indirect antiglobulin (Coombs) test

Saline suspension of red cells of donor is incubated with patient’s serum. Washed in saline and antiglobulin agent is added. Re-centrifuge and examine for agglutination or hemolysis. It will detect of any IgG antibodies in patient’s (recipient’s) serum.

Interpretation

•• If there is no agglutination or hemolysis it indicates compatibility of donor unit with patient’s (recipient’s) serum.

•• Agglutination or hemolysis indicates incompatibility and should not be transfused.

Antibody screening and identification

Patient’s (recipient’s) serum should be tested for the presence of clinically significant (unexpected or irregular) antibodies. In this procedure, serum of the recipient is tested against a set of three group O screening cells of known antigenic type. If clinically significant antibodies are identified, the blood unit without the corresponding antigens is selected for compatibility test.

Supervision of Blood Transfusion

•• To observe and identify if any reactions develop and management of the complication.

BLOOD COMPONENTS (FIG. 60.2)

It is possible to separate different components of blood from a single unit of whole blood. These components can be used individually to help more than one patient with many purposes. Thus, red cells can be transfused to an anemic patient and plasma for a burns patient. 

This also ensures that only the required components are transfused. The various blood components are:

•• Whole blood: Indications listed in Box 60.1.

•• Red cells concentrate or packed red blood cells(PRBCs)

•• Platelet concentrates

•• Plasma

•• Fresh frozen plasma (FFP)

•• Cryoprecipitate.

Red Cells Concentrate or Packed Red Blood Cells (PRBCs)

Packed red cells are obtained by centrifugation/sedimentation of the whole blood and the plasma is transferred to another bag. In the packed red cell unit, the hematocrit is between 55% and 65%. Since, the volume is only 200 mL; there is less risk of volume overload. One unit of packed red blood cells raises hemoglobin concentration by 1 g/dL. These are stored in a refrigerator/cold room at 2° to 4°C and its shelf-life is one month. Indications for PRBCs is listed in Box 60.2. 

Other red cell components include:

(1) red cells in additive solution, 

(2)leukocyte-poor red cells, 

(3) washed red cells, 

(4) frozen red cells, and 

(5) irradiated red cells.

Platelet Concentrate

Platelet concentrate may be obtained from a single donor or pooled plasma. Platelets can also be obtained from a single donor by platelet apheresis. They are stored at 20° to 24°C and have shelf-life of 5 days. Platelets have ABO antigens on their surface but do not express Rh antigen. But it is advisable to transfuse Rh negative persons with platelets only from Rh negative persons. Indications for platelet concentrate is presented in Box 60.3.

Each unit of platelets usually increase the platelet count by 5,000 to 10,000/cu mm.

Plasma

Plasma is separated from red cells by centrifugation of the whole blood. The red cells are used as packed red cell component. Plasma may be used to replace the lost plasma proteins in cases of extensive burns.

Fresh Frozen Plasma

Fresh frozen plasma (FFP) is plasma (after separation from red blood cells) along with anticoagulant preservative frozen immediately at–2°C. It contains maximum levels of labile and non-labile clotting factors and include albumin, protein C and S and antithrombin. FFP has a shelf-life of 1 year.

Indications for fresh frozen plasma is presented in Box 60.4.

Cryoprecipitate

It is the cold insoluble portion of plasma that precipitates when FFP is thawed (melted) between1° and 6°C. It contains concentrated precipitate of Factor VIII, XIII, vWF and fibrinogen.

Indication

Hemophilia, factor XIII deficiency, von Willebrand disease and hypofibrinogenemia

Apheresis

It is the method of collection of anticoagulated whole blood from donor, its separation into components, retention of the desired components and returning the remaining constituents to the donor itself. Indications for apheresis are mentioned in Box 60.5.

Granulocyte Transfusion

It is not frequently employed, because it is preferable to administer the growth factors for myelopoies is like G-CSF/GM-CSF. But it is indicated when granulocyte count is less than500/cu mm (agranulocytosis), and to combat infections (in neonatal sepsis and chronic granulomatous disease).

Plasma Derivatives

Plasma derivatives are prepared by fractionation of large volumes of polled human plasma. Important plasma derivatives are presented inTable 60.5.

TRANSFUSION REACTIONS

Blood transfusion is useful and life saving when performed with caution and with clear indication. Sometimes (about 2–4% of cases) unfavorable complications occur in spite of precaution and preventive measures, which are known as transfusion reactions. They may be broadly divided into infectious and noninfectious complications (Box 60.6).

Box 60.6: Complications of blood transfusion

Noninfectious Complications

Transfusion reactions may result from immune and nonimmune mechanisms.

Immune-mediated (Immediate and Delayed) Reactions

Acute hemolytic transfusion reaction

•• ABO incompatibility between recipient and donor, resulting in destruction of donor cells. This is brought out by the naturally occurring (preformed) antibodies namely anti-A and anti-B (depending on the blood group).

–– Massive intravascular hemolysis: This is one of the serious complications which develop within 1 to 4 hours and with only a few milliliters of incompatible red cells. The preformed IgM antibodies (anti-A and anti-B) in the recipient coat transfused donor red cells and activate complement system to form membrane attack complex (C5-9). This results in intravascular destruction (hemolysis) of transfused donor red blood cells.

◆◆ Patient typically develops fever with chills, pain in the lumbar region, dyspnea, tachycardia and hypotension.

◆◆ Intravascular hemolysis results in hemoglobinuria and oliguria with acute renal failure. Red cell lysis may result in disseminated intravascular coagulation.

◆◆ In majority of cases, this results from clerical errors like wrong labeling of the crossmatch sample, improper checking or transfusion to the wrong recipient.

◆◆ Treatment consists of immediate interruption of transfusion, immunosuppression with corticosteroid therapy and management of the renal failure.

•• Rh incompatibility: Because anti-Rh antibodies are not complement-fixing, in Rh incompatibility hemolysis develops in the extravascular compartment.

 Delayed hemolytic transfusion reaction

In the recipient, if antibody titer is too low and weak to be detected during cross-match, it may not cause immediate hemolysis at the time of transfusion. Instead, it may lead to a gradual increase in the antibody titer causing delayed, gradual lysis of donor red cells and is known as a delayed hemolytic transfusion reaction. The features are:

•• It is mild and is due to extravascular hemolysis caused by HLA antibodies.

•• Develops 4–14 days after transfusion.

•• Mostly asymptomatic and characterized by unexplained anemia and jaundice.

Febrile nonhemolytic reaction

Patient develops fever, chills, rigors and headache 30–60 minutes after transfusion. It is due to sensitization to leukocyte antigens.

Allergic reaction

Allergic reaction manifests as urticaria (hives), fever, bronchospasm and rarely anaphylactic shock. It is due to exposure of allergens in donor’s plasma to IgE antibodies in recipient’s plasma, which activates mast cells and releases histamine/leukotrienes.

Transfusion-related acute lung injury (TRALI)

•• Cause: TRALI usually develops from the transfusion of donor plasma that contains high titer anti-HLA antibodies that bind recipient leukocytes. This produces aggregation of leukocytes in the pulmonary vasculature and release mediators that increase capillary permeability. Such antibodies are most frequently found in females after pregnancy and are not found in plasma of males unless they have been transfused.

•• Patient develops an acute respiratory distress, either during or within 6 hour of transfusing the patient. It is characterized by fever, cough, shortness of breath and typical bilateral interstitial infiltrates on chest X-ray. The reaction occurs during or soon after transfusion and may be life threatening.

Transfusion-associated graft versus host disease (TA-GVHD)

Transfusion associated GVHD is a rare but potentially fatal complication of blood transfusion. This may develop 10–12 days after transfusion.

Mechanism: Donor blood products contain mature T cells which attack recipient’s tissues. It is observed more commonly in immunocompromised recipients. Clinical features include fever, generalized skin rash, jaundice, diarrhea and features of pancytopenia (due to marrow failure). TA-GVHD can be prevented by transfusing the irradiated blood/components in patients at risk.

Nonimmunological (Immediate and Delayed) Reactions

Circulatory overload

Following whole blood transfusion, the blood volume and venous pressure also increases. This may be significant in the elderly, pregnant women and those with reduced cardiac function resulting in acute pulmonary edema. This can be avoided using blood components like packed red blood cells.

Air embolism

This was common earlier when transfusion was given from the glass bottle. Presently, due to the use of plastic bags with closed tubing system, this complication does not develop.

Iron overload (transfusion siderosis)

•• This is seen in patients who receive multiple transfusions over a period of few years (e.g. thalassemia). The excess iron gets deposited in reticuloendothelial cells of spleen, bone marrow, liver, heart and endocrine glands.

•• Iron overload can be prevented or reduced by giving iron chelating agents (like Desferal).

Thrombophlebitis

Inflammation of vein may develop in patients with indwelling catheters.

 Massive transfusion

If the volume of stored blood transfused to bleeding patients exceeds patient’s normal blood volume, it may lead to dilutional thrombocytopenia and dilution of coagulation factors.

Infectious Complications

Transfusion of infected blood may transmit few diseases like AIDS, hepatitis (HBV, HCV and HDV), HTLV-I and II, malaria and cytomegalovirus infection. This is prevented by screening the donors for these common and ominous infections.

EXCHANGE TRANSFUSION

When blood is withdrawn from one vein and is replaced with fresh blood from another vein, it is called as an exchange transfusion. It is usually done to remove the red cells (e.g. in HDN) or antibodies(e.g. TTP, HDN). Indications for exchange transfusion is presented in Box 60.7.

Points to note:

•• Transfusion medicine comprises transfusion of blood and blood components.

•• Blood donor should be healthy and the blood is collected in a plastic bag with CPD-A as an anticoagulant.

•• Before transfusion of blood or its components, compatibility testing has to be done.

•• The various blood components include: packed red blood cells, platelet concentrate, plasma, fresh frozen plasma and cryoprecipitate.

•• Transfusion reactions may be infectious and noninfectious. The noninfectious complications may be immediate or delayed and both of which may be brought out by immunological or nonimmunological mechanisms.

•• Transfusion may transmit disease like AIDS, hepatitis, malaria and CMV.