Audra L. McCreight
Jonathan E. Wickiser
• It is common to underestimate quantitative blood loss in the setting of trauma. Careful and frequent monitoring of vital signs and hematocrit is critical in the detection of severe hemorrhage.
• Massive transfusion protocols exist to supply O-negative blood and other essential blood products for the resuscitation of the hemodynamically unstable trauma patient.
• Mild-to-severe reactions can occur during the transfusion process including fever, chills, nausea, hypotension, or shock. Whether this is caused by blood type incompatibility, antibodies to donor cells, or blood product contamination, the transfusion must be stopped immediately and the symptoms of the reaction treated aggressively.
Transfusion of blood and blood components is often necessary in the emergency department (ED). Whole blood, packed red blood cells (PRBCs), platelets, granulocytes, fresh frozen plasma (FFP), cryoprecipitate, specific clotting factors, albumin, and immunoglobulins each have specific indications and risks associated with their use. As blood for transfusion is a scarce commodity, the component that will specifically address the patient’s need is generally transfused.
Transfusion of whole blood is rarely performed but may be indicated for prompt restoration of red cells and volume after trauma or surgery. After 24 hours of storage, platelets and granulocytes contained within whole blood have lost function. Activity of labile clotting factors V and VIII is also diminished greatly within 3 to 5 days. The risk of transfusion reactions with whole blood is doubled owing to the volume of foreign proteins and antibodies that it contains.1
PACKED RED BLOOD CELLS
PRBC units contain approximately 50 mL of plasma and have a hematocrit ranging from 55% to 80%, depending on the preservative used for storage. Units are stored in solution with anticoagulant and preservative for up to 42 days. There are no functional platelets or granulocytes in this preparation. For patients with a previous history of febrile reactions to transfusions or if the risk of cytomegalovirus (CMV) transmission is to be particularly avoided, filtered, leukocyte-poor red cells are recommended. Leukocyte depleted preparations contain <5 × 106 leukocytes per unit.2 In many institutions all PRBC units are routinely leukocyte depleted.
Platelet concentrates are obtained by either pooling multiple individual platelet concentrates from approximately four to eight individual whole blood donors (commonly known as a “6-pack”) or from plateletpheresis of a single donor. There may be advantages to the reduced donor exposure of single donor product; however, platelet product choice varies by institution and availability. Products usually contain approximately 5.5 × 1010 platelets in approximately 50 mL of plasma. They should be ABO and Rh compatible, but crossmatching is not necessary. In children, the dose is estimated at 0.1 to 0.2 U/kg of random donor platelets required to raise the platelet count by 50,000 to 100,000/μL. Platelet transfusions are indicated for patients with active bleeding due to thrombocytopenia or platelet dysfunction. Counts above 20,000/μL rarely result in spontaneous bleeding, but at counts below 10,000/μL, the risk is severe. Patients with immune thrombocytopenia or thrombotic thrombocytopenic purpura do not benefit from platelet transfusions except in cases of life-threatening hemorrhage since the ongoing antibody-mediated disease process destroys the transfused platelets rapidly.2
Transfusion of white cells is indicated only in a severe, prolonged neutropenic patient with documented or strongly suspected antibiotic resistant sepsis. The use of granulocyte infusions is controversial and should only be done under the advisement and supervision of a pediatric hematologist.
FRESH FROZEN PLASMA
FFP is produced by freezing plasma shortly after collection. It consists of the noncellular components of blood including procoagulant clotting factors such as factors V and VIII, the anticoagulants protein S, protein C, and antithrombin III. ABO compatibility is important, but crossmatching is not necessary. The most common indications for using FFP include situations where multiple factor deficiencies are present simultaneously. Table 106-1reviews the indications for use of FFP. It is used at a dose of 10 to 20 mL/kg infused to gravity. The risk of disease transmission is similar to that of whole blood transfusion and allergic reactions are possible. FFP is not indicated for acute volume expansion.2
Indications for use of Fresh Frozen Plasma
Cryoprecipitate is prepared by slow thawing of FFP at 4°C and subsequent refreezing for storage of the protein precipitate, which is rich in fibrinogen, factor VIII:vWf, and factor XIII. This is a purely procoagulant preparation as compared to FFP, which also contains physiologic anticoagulants protein C and protein S. Cryoprecipitate does not require crossmatching. It is indicated for treatment of hypo- or a-fibrinogenemia. Cryoprecipitate use in hemophilia A, von Willebrand disease, or factor XIII deficiency should only be considered when the specific factor concentrate is not available. In pediatrics, one unit of cryoprecipitate is given per 5 kg of body weight.2
FACTORS VIII AND IX
Highly purified concentrates of factors VIII and IX are now produced by monoclonal antibody techniques and by recombinant DNA technology. A number of such products are available and have replaced single donor products such as FFP in the treatment of hemophilia.
Available in both 5% and 25% solutions, albumin is most frequently used for blood volume expansion in shock, trauma, burns, and surgery. Heat and chemical treatment eliminates the infectious transmission risk and it contains no blood group antibodies. Only the 5% solution is isosmotic with plasma, and the 25% solution is never used to treat shock without other fluids.
These antibody-rich preparations are occasionally used in the ED to treat conditions such as rabies and tetanus, as postexposure disease prophylaxis. It is also a mainstay of therapy in other immune-mediated diseases such as Kawasaki disease.2
INDICATIONS FOR TRANSFUSION
The most common scenario in the ED requiring blood transfusion is the hemodynamically unstable trauma patient. Most other anemic patients are hemodynamically compensated, and transfusion can be carried out after admission. The rapidly exsanguinating trauma patient has both quantitative and qualitative transfusion requirements. Recently, several institutions have developed massive transfusion protocols to address these needs. Massive transfusion generally refers to the replacement of a patient’s total blood volume in less than 24 hours, or as the acute replacement of more than half the patient’s estimated blood volume in any 3-hour period. These protocols were designed to support rapid transfusion in the ED with O-negative blood (universal donor) and blood products such as platelets and FFP that are released from the blood bank automatically upon provider request. Although the ideal amounts of plasma, platelet, cryoprecipitate, and other coagulation factors in relationship to the RBC transfusion volume are not known, current data support a target ratio of RBCs:platelets:plasma transfusions of 1:1:1.
The risks of minor blood group incompatibility causing hemolysis or recipient sensitization to RBC antigens are overshadowed in this situation. Early and aggressive resuscitation with blood components is the accepted approach to major trauma that addresses the lethal triad of acidosis, coagulopathy, and hypothermia. Failure to provide sufficient volume and coagulation support increases the risk of mortality in the trauma patient.3
Conversely, patient-specific blood typing should be done in the hemodynamically stable patient. Blood typing (for ABO and Rh) is a rapid screening process for antibodies and crossmatching, finding donor blood that the patient’s body will accept. This process may take 60 minutes or more.
• if Hgb >10 g/dL, transfusion is rarely indicated
• if Hgb <5 g/dL, transfusion is usually necessary
• if Hgb is between 5 and 10 g/dL, clinical status is helpful in determining transfusion requirements
The decision to transfuse is ultimately determined by clinical status. In general, the history of blood loss in a given patient is often inaccurate and the initial hemoglobin may not reflect losses, so it is crucial to monitor heart rate and blood pressure for changes of early shock.4
There are several types of transfusion reactions, which range from mild to life threatening. In the event of a reaction, the transfusion is stopped and the blood bank is notified. Care in collecting and labeling specimens for the blood bank is crucial.
ACUTE HEMOLYTIC TRANSFUSION REACTIONS
Acute hemolytic transfusion reactions (AHTR) occur when a patient’s anti-A or anti-B antibodies bind to incompatible transfused red cells. These reactions are seen immediately and are almost always the result of errors in labeling of specimens. The transfused cells are lysed, releasing inflammatory mediators.
Symptoms usually begin with an increase in body temperature and pulse rate. Other symptoms may include chills, back or flank pain, nausea and vomiting, dyspnea, flushing, abnormal bleeding, and hypotension. Disseminated intravascular coagulation (DIC), shock, renal failure, and death may ensue. Laboratory findings can include hemoglobinemia and/or hemoglobinuria, an increased serum bilirubin, and a positive direct antibody test. Aggressive fluid resuscitation with normal saline to maintain blood pressure and urine output should be initiated, as well as specific therapies to correct any associated coagulopathy.2
DELAYED HEMOLYTIC TRANSFUSION REACTIONS
Delayed hemolytic transfusion reactions (DHTR) are caused by sensitization to non-ABO antigens from a previous transfusion. The most prominent signs and symptoms are unexplained anemia, jaundice, fever, back pain, and rarely, hemoglobinemia and/or hemoglobinuria. DHTR are detected 3 to 14 days after transfusion, the previously transfused patient’s hemoglobin is below expected values with a history of fever and jaundice. No treatment is usually required.2
FEBRILE NONHEMOLYTIC TRANSFUSION REACTIONS
Febrile or nonhemolytic transfusion reactions (FNHTR) are benign and self-limiting; they account for the great majority of transfusion reactions and occur most commonly in the multiply transfused patient. Symptoms include fever and chills that may be difficult to distinguish from AHTR; therefore, if the patient is very uncomfortable, the transfusion should be stopped. Antipyretics may be given. FNHTR are caused by recipient antibodies to antigens on donor leukocytes and platelets. There are no laboratory tests available to predict or prevent these reactions; however, the parent or the patient can often give a history of previous FNHTR, allowing intervention with antipyretics prior to transfusion if prior reactions were severe or frequent.2
ALLERGIC TRANSFUSION REACTION
Allergic transfusion reactions are of three types, each with different etiologies.
• Urticarial reactions may involve allergens, cytokines, or histamine in stored blood products. The transfusion must be interrupted and the patient watched closely for signs and symptoms of anaphylaxis. An antihistamine such as diphenhydramine (1 mg/kg) should be administered. When the urticaria fades, transfusion can be resumed.
• Anaphylactic reactions are severe urticarial reactions that commonly occur in patients with congenital IgA deficiency who have high-titer IgG anti-IgA antibodies. Activation of a complement and chemical mediator cascade precipitates increased vascular permeability, resulting in angioedema, respiratory distress, urticaria, and shock. The transfusion is stopped, epinephrine is administered (0.01 mg/kg 1:1000 subcutaneously), and blood pressure is stabilized with crystalloid and vasopressive agents if necessary.
• Transfusion-related acute lung injury (TRALI) occurs when the permeability of the pulmonary microvasculature is acutely increased, which leads to massive pulmonary edema, usually within 6 hours of transfusion. It is thought to be related to the presence of granulocyte antibodies in either the donor product or the recipient although the specific mechanism is still unknown. Therapy consists of rapid and aggressive pulmonary support.4
COMPLICATIONS OF MASSIVE TRANSFUSIONS
Disturbances in coagulation can occur with massive transfusion therapy.5 Table 106-2 summarizes complications that may occur when large amounts of whole blood or PRBCs are given rapidly. Dilutional thrombocytopenia can be seen when 1.5 times the blood volume must be replaced or when there is pre-existing thrombocytopenia or DIC. Each unit of PRBCs contains approximately 3 g of citrate, which will bind ionized calcium. In a healthy patient, the liver will metabolize 3 g of citrate every 5 minutes. At transfusion rates greater than one unit per 5 minutes or with impaired liver function, citrate toxicity occurs leading to hypocalcemia causing tetany or hypotension. Hyperkalemia can occur with rapid transfusion of PRBCs because the concentration of potassium in stored blood increases with storage. Hypokalemia is also common as transfused RBCs begin active metabolism and intracellular reuptake of potassium. Other complications that can occur include hypothermia if a blood warmer is not used, disturbances in acid/base status, and acute respiratory distress syndrome (ARDS).2
Complications of Massive Transfusion Therapy
Donated blood is routinely screened for HIV-1 and -2, HTLV, hepatitis B surface antigen, hepatitis B core antibody (a surrogate marker for non-A, non-B hepatitis), hepatitis C virus, and syphilis. The estimated risk of transmitting HIV through a blood transfusion is 1 in 146,7000 units transfused; hepatitis B, 1 in 282,000 units transfused; and hepatitis C, 1 in 1,149,000 units transfused.2
Bacterial contamination of blood products can occur and accounts for other transfusion reactions and fatalities. Fever, chills, rigor, vomiting, and hypotension present soon after the transfusion is begun. Blood cultures should be sent from the patient and from the blood product. AHTR is in the differential if the patient is receiving RBCs, and samples (blood and first voided urine) should be sent to the blood bank to check for hemolysis.1
1. Dodd RY, Notari EP, Strainer SL. Current prevalence and incidence of infectious disease markers and estimated window period risk in the American Red Cross Blood Donor Population. Transfusion. 2003;42:975–979.
2. Quraishy N, Bachowski G, Benjamin R, et al. A Compedium of Transfusion Practice Guidelines. 1st ed. Washington, DC: American Red Cross; 2010.
3. Shah BH, Dente CJ, Harris RS, MacLeod JB, Hillyer CD. Transfusion management of trauma patients. Anesth Analg. 2009;108:1760–1768.
4. American Association of Blood Banks. Technical Manual. 17th ed. Bethesda, MD: AABB Press; 2011.
5. Hendrickson JE, Shaz BH, Pereira G, et al. Coagulopathy is prevalent and associated with adverse outcomes in transfused pediatric trauma patients. J Pediatr. 2012;160(2):204–209.e3. doi: 10.1016/j.jpeds.2011.08.019. Epub 2011 Sep 16.