Chapter 91: Red Cell Transfusion

• Erythrocytes are preserved by liquid storage at 4°C or by frozen storage at either –80°C or –150°C.

• Preservative solutions for liquid storage all contain glucose, to provide energy, and citrate buffer at an acid pH to prevent coagulation by binding calcium and to counter the marked rise in pH that occurs when blood is cooled to 4°C.

• CPD-adenine is the preservative solution most frequently used in the United States at present. It contains adenine, citrate, phosphate, and dextrose (glucose).

• Adenine is added to help maintain intracellular levels of ATP.

• Erythrocytes are then separated and stored in an additive solution that contains glucose, adenine, and mannitol.

• The remainder of the blood collection is separated into plasma and platelets.

• Stored erythrocytes develop the so-called storage lesion, characterized in part by reduced levels of ATP, which interfere with glucose metabolism and reduce cell viability. 2,3-Bisphosphoglycerate levels also rapidly fall during storage, which increase the oxygen affinity of hemoglobin and thereby decreases the initial effectiveness of reinfused red cells. Potassium also leaks rapidly from stored cells.

• Frozen storage requires a cryoprotective agent to avoid hemolysis during freezing and thawing. Glycerol is the most frequently used agent. With proper technique, more than 80% of erythrocytes will survive frozen storage and function normally after transfusion.

• A unit of whole blood contains 435 to 500 mL of blood and 14 to 15 mL of preservative-anticoagulant solution for each 100 mL. Thus, if 450 mL of blood is collected, stored, and transfused, the patient will receive about 515 mL of total fluid.

• Blood collected in CDPA-1 (CDP with adenine) may be used after storage up to 35 days.

• There are very few, if any, indications for whole blood, and it is rarely used in modern transfusion practice.

• When blood is stored, platelet viability is lost within 48 hours, and the activity of coagulation factors V, VIII, and IX falls significantly.

• Thrombocytopenia and deficiency of the labile coagulation factors may occur in patients who receive transfusions of banked blood equal to their total blood volume in 24 hours.

• Fresh blood is often requested in an effort to avoid administration of blood deficient in these hemostatic components.

• It is better to treat such patients with a combination of packed red cells, fresh-frozen plasma, and platelet concentrates.

• Whole blood or packed red blood cells less than 5 to 7 days old should be transfused to patients with severe renal or hepatic disease or to newborns receiving exchange transfusion in order to avoid infusing excess free potassium.

• Patients who require massive transfusion should be given at least part of the transfusion as blood less than a few days old in order to avoid oxygen release problems caused by depletion of red cell 2,3-bisphosphoglycerate and to prevent replacement with platelet-poor blood.

• Patients with chronic transfusion-dependent anemia should probably receive blood less than 10 days old in order to maximize the interval between transfusions and to minimize iron accumulation.

• Packed red blood cells can be prepared from stored blood any time before the expiration date by centrifugation and removal of plasma to give a hematocrit of 60% to 90%.

• Red cells packed to a hematocrit of less than 80% can be stored until the expiration date of the original blood.

• Red cells, rather than whole blood, should be used for replacement of a red cell deficit.

• Packed red cells and electrolyte solutions are as effective as whole blood in replacing surgical blood loss.

• Leukocyte-poor blood is best prepared by passing blood or packed cells through a special filter that removes leukocytes.

• It is used to prevent or avoid febrile reactions to leukocytes or platelets in previously sensitized patients; to minimize transmission of viral diseases, such as HIV or cytomegalovirus infections; and perhaps in patients awaiting kidney transplant.

• Washed red cells are obtained from whole blood by centrifugation techniques.

• They must be used within 24 hours of preparation because of the danger of bacterial contamination.

• These cells are indicated for patients who are hypersensitive to plasma.

• They are sometimes used in neonatal transfusions to reduce the amount of anticoagulant, extracellular potassium, etc., infused.

• Frozen red cells may be stored for years but cost two to three times as much as stored liquid blood.

• They are somewhat leukocyte poor and almost free of plasma.

• They may be used for autotransfusion, to ensure a supply of rare blood, or to reduce sensitization to histocompatibility antigens in potential transplant patients.

• Informed consent should be obtained and documented before transfusion therapy is given.

Hemorrhage and Shock

• Volume support is of primary concern, but replacement of red cells is also necessary with larger losses of blood.

• Packed red cells with crystalloids or albumin are as effective as whole blood in replacing volume loss.

Surgery

• Blood loss (even >1000 mL) may be safely replaced with crystalloids.

• Because of the hazards of blood transfusion (see below), every effort should be made to minimize the use of blood for volume replacement in surgery.

Burns

• Severe burns require extensive volume replacement in the first 24 hours.

• Plasma loss occurs over the next 5 days and can be replaced with plasma and colloids.

• Anemia can be treated with packed red cells.

Anemia

• Patients with stable anemia with a hemoglobin level above 7 g/dL should not be transfused unless they are elderly or have cardiac or pulmonary disease.

• Attempts to improve the efficiency of transfusion by increasing the red blood cell circulation times by using young red cells (“neocytes”) have had limited success.

• It is essential that the person administering blood or a blood component read the label to ensure that the unit to be used was selected by the laboratory for the particular patient.

• Usually blood does not need to be warmed when given to adults unless amounts greater than 3 L are to be given at greater than 100 mL/min. At the usual rate of administration, the aggregates that may develop in patients with high-titer cold agglutinins may be dispersed when the blood reaches body temperature.

• Blood being given to patients with cold agglutinins or cryoglobulinemia should be warmed to prevent further vascular damage.

• Blood should be given slowly in the first 30 minutes to minimize an adverse reaction.

• Drugs or medications should not be added to blood or blood components.

Autologous Transfusions

• Such transfusions minimize the probability of adverse reactions to transfusion, such as transmission of disease or alloimmunization.

• They may be achieved by preoperative collection and storage of blood, immediate preoperative phlebotomy and hemodilution with postoperative return of the blood, or reinfusion of blood collected intraoperatively.

• In some patients, erythropoietin has been given to permit increasing the amount of blood taken preoperatively. Approximately one additional unit of blood can be collected if the patient is supplemented with erythropoietin, making the actual benefit questionable.

• Autologous donation is ideal for patients with rare blood types or with antibodies that make cross-matching difficult or impossible.

Directed or Designated Donations

• Donors recruited from among family or friends are no safer than volunteer blood donors. Graft-versus-host disease in stem cell transplant recipients receiving transfused blood products is a greater risk if blood is donated by family members.

• The majority of fatal transfusion reactions are due to management-clerical errors.

• Up to 20% of all transfusions may lead to some type of adverse reaction.

Immediate Reactions

Acute Hemolytic Reactions

• These reactions may occur intravascularly, usually because of ABO incompatibility, or extravascularly.

• Intravascular hemolysis may lead to disseminated intravascular coagulation (DIC) or to ischemic necrosis of tissues, particularly the kidney.

• Patients may develop fever, low back pain, sensation of chest compression, hypotension, nausea, or vomiting.

• The transfusion should be terminated immediately when an acute reaction is suspected, and measures to control hemorrhage, if present, and to prevent renal damage instituted promptly.

• Laboratory diagnosis is based on evidence of hemolysis (hemoglobinemia, methemalbuminemia, hemoglobinuria) and detection of a blood group incompatibility.

• Renal damage may be prevented by hydration with addition of a diuretic if necessary to maintain urinary flow greater than 100 mL/h. Mannitol may be used at an initial dose of 100 mL of a 20% solution given intravenously over 5 minutes. Furosemide in a dose of 40 to 80 mg intravenously may be more effective.

• If oliguria occurs, standard measures for acute renal failure should be instituted.

• The risk of sequelae is dependent on the amount of incompatible blood given. Severe complications rarely occur if fewer than 200 mL of red cells have been transfused.

Febrile Reactions

• Fever may be caused by a hemolytic reaction, sensitivity to leukocytes or platelets, bacterial pyrogens, cytokines released by stored leukocytes or unidentified causes.

• Thirty percent of all transfusion reactions are nonhemolytic, febrile reactions.

• A febrile reaction of itself is not an indication for termination of the transfusion, but one should not hesitate to stop if there is any doubt about the cause.

• Chills may indicate a more serious situation, but there are no reliable guidelines.

• Sensitization to leukocyte or platelet antigens is a common cause of febrile reactions.

• At least seven transfusions are usually required for sensitization, but previously pregnant women may be sensitized after only one or two.

• Clinical findings are primarily fever, which may continue to rise for 2 to 6 hours after the transfusion is stopped and may continue for 12 hours.

• Diagnosis depends on demonstration of antibodies to leukocyte or platelet antigens. Most reactions are a result of antibodies to granulocytes.

• Treatment is supportive.

• Many reactions can be prevented by use of a leukocyte filter, especially if applied to the unit of blood shortly after collection.

Transfusion-Related Acute Lung Injury

• Transfusion-related acute lung injury (TRALI) is a syndrome of acute hypoxia as a result of noncardiogenic pulmonary edema that follows transfusion. All blood components have been implicated in TRALI, but most frequent are plasma-containing products, which account for 50% to 63% of TRALI fatalities.

• The precise mechanisms of the capillary leak syndrome in TRALI have not been fully determined, but two main hypotheses have been proposed. One involves white cell antibody-mediated TRALI and the other cytokine-mediated TRALI.

• It is often impossible to distinguish TRALI from acute respiratory distress syndrome. The typical presentation of TRALI is the sudden development of dyspnea, severe hypoxemia (O₂ saturation <90% in room air), hypotension, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours. Although hypotension is considered one of the important signs in diagnosing TRALI, hypertension can occur in some cases.

Pulmonary Hypersensitivity Reaction (Noncardiogenic Pulmonary Edema)

• Leukocyte incompatibility may also cause acute respiratory distress, chills, fever, and tachycardia as a consequence of pulmonary edema.

• Donor leukocytes may react with recipient antibodies, or donor antibodies may react with recipient leukocytes.

• Almost 25% of multiparous women have antibodies that can cause this reaction.

• This reaction can occur with transfusion of platelets, plasma, whole blood, or packed red cells.

• Onset is usually within 4 hours of transfusion.

• Chest films show bilateral diffuse, patchy pulmonary densities without cardiac enlargement.

• Treatment is supportive.

• In a healthy individual, symptoms subside in less than 24 hours, and the pulmonary infiltrates disappear within 4 days.

Allergic Reactions

• Transfusion may result in generalized pruritus and urticaria, and occasionally there may be bronchospasm, angioedema, or anaphylaxis.

• The cause is poorly understood, but may be hypersensitivity to plasma proteins or other substances in the administered product.

• These reactions are usually mild and respond to antihistamine drugs, but epinephrine may be required in some cases.

Anti-IgA in IgA-Deficient Recipient

• Severe anaphylactic reactions may occur in IgA-deficient patients who have formed anti-IgA antibodies.

• Deficiency or absence of IgA occurs in about 1 in 800 people.

• IgA in the transfused product reacts with circulating antibody in the recipient. Less than 10 mL plasma can cause a reaction.

• Symptoms are dyspnea, nausea, chills, abdominal cramps, emesis, diarrhea, and profound hypotension. There is no fever.

• Diagnosis depends on demonstration of IgA deficiency and anti-IgA antibodies in the recipient.

• Reactions can usually be prevented by using washed red cells. Platelet or granulocyte transfusions for sensitized patients should be from donors with absent IgA.

Bacterial Contamination

• Blood may be contaminated by cold-growing organisms (Pseudomonas or coli-aerogenes group) that utilize citrate and may therefore lead to formation of visible clots.

• Infusion of blood containing large numbers of gram-negative organisms leads to endotoxin shock, with fever, hypotension, abdominal pain, vomiting, diarrhea, and vascular collapse, beginning immediately after infusion is started or 30 minutes or more after the infusion.

• Diagnosis may be made by examining a Gram stain of plasma obtained by low-speed centrifugation of some of the transfused blood. If the blood is heavily contaminated, organisms should be seen in every oil immersion field.

• Bacterial contamination of blood is uncommon if disposable plastic blood bags are used, but contamination may be a significant hazard with platelet concentrates stored at room temperature.

Circulatory Overload

• Congestive heart failure with pulmonary edema may develop following transfusion in patients with cardiovascular compromise. Treatment is primarily with diuretics.

• Patients with severe chronic anemia may also develop congestive heart failure if transfused rapidly. Diuretics should be given and the transfusion limited to 2 mL/kg per hour.

Microaggregates in Blood

• Particles of 13 to 100 microns in size (“microaggregates”) and consisting largely of platelets and fibrin in banked blood are not removed by the usual filters in transfusion sets.

• Such particles can cause pulmonary insufficiency when massive transfusion of banked blood is given using standard filters, but this can be prevented with microaggregate filters.

Citrate Intoxication

• Blood transfused into adults at a rate greater than 1 liter in 10 minutes will cause significant reduction in ionized calcium concentrations and lead to myocardial depression and electrocardiographic changes.

• This can be prevented by giving 10 mL of 10% calcium gluconate intravenously for every liter of citrated blood administered.

Delayed Reactions

Delayed Hemolytic Reaction

• Previously undetected alloantibodies may appear 4 to 14 days after a first transfusion and cause destruction of the transfused cells. An anamnestic response immediately following transfusion can occur in patients who had been previously transfused or pregnant if the relevant antigen is presented to the patient.

• Clinical findings are jaundice, falling hemoglobin level, and a positive direct antiglobulin reaction (Coombs test). The blood bank can usually differentiate if a positive Coombs test is from alloantibodies or from non–transfusion-related autoantibodies.

• Delayed hemolytic reactions may be mild and probably are frequently undetected.

Post-transfusion Purpura

• Thrombocytopenia caused by antibodies to a platelet-specific antigen may develop shortly after transfusion (see Chap. 73).

Transmission of Disease

• The greatest risks are viral agents such as hepatitis B or C or HIV, although with current blood donor screening procedures the risk of each of these infections is less than 1:1,000,000.

Other Adverse Effects

• Graft-versus-host disease is an uncommon complication of transfusion, preventable by administering irradiated blood.

• Iron overload may occur in patients who require chronic transfusion therapy (see Chap. 9).

• Alloimmunization to antigens not included in routine cross-matching occurs in immunocompetent patients receiving multiple transfusions and creates a major problem in obtaining blood for some patients with chronic anemia.