Blood and Blood Components
Perspective
The modern blood transfusion era began with discovery of the ABO red cell antigen system in the early 1900s. It was soon found that adding citrate enabled the storage of anticoagulated blood. Blood banking in the United States began during the 1930s. Energetic pioneers, such as John Lundy of the Mayo Clinic, gained a wealth of clinical experience, prompting dissemination of expert-based advice, such as Lundy’s recommendation that blood transfusion was appropriate when a patient’s hemoglobin (Hgb) was less than 10 g/dL or when a patient lost more than 15% of circulating blood volume. These recommendations were not, however, based on rigorous controlled trials. Rapid expansion of blood banking occurred after World War II, and in subsequent decades, research focused on such critical issues as prolonging the storage life of blood products, component therapy, and reducing the risk of transfusion reactions and transfusion-related infections.1,2
More recently, at a time when more than 14 million units of packed red blood cells (PRBCs) are transfused yearly in the United States, research has increasingly focused on developing a more evidence-based approach to identification of appropriate transfusion triggers for all blood components, developing massive transfusion protocols, and reassessing the overall risks and benefits of transfusion.3–10
Pathophysiologic Principles
Although traditional allogenic donation methods still predominate, increasing use is being made of red cell apheresis technology (about 10% of all units donated), by which red cells are separated from the blood at the time of collection, with everything else returned to circulation. This allows collection of about two transfusable units during a single donation. Autologous blood collection, in which the donor is also the intended recipient, peaked in the early 1990s and continues to decline.11
Red blood cell (RBC) storage methods aim to ensure viability of at least 75% of the cells 24 hours after infusion.12 Blood collection bags contain an anticoagulant preservative of citrate, phosphate, dextrose, and adenine (CPDA-1), ensuring a shelf life of 35 days and hematocrit of 70 to 80% for PRBCs. Additive solutions (Adsol, Nutricel, Optisol) provide additional nutrients, extending maximum storage to 42 days and lowering viscosity, which makes infusion easier.13
Storage, however, impairs red cell function.14 Stored blood initially delivers oxygen to the tissues less efficiently. Although PRBCs are maintained at 1 to 6° C, cell metabolism continues, and changes occur. These changes are collectively referred to as the “storage lesion.”14 Documented alterations are numerous and include a decrease in both pH and the level of 2,3-diphosphoglycerate (2,3-DPG). In addition, the deformability of stored RBCs changes over time, making them more spherical and rigid, increasing resistance to capillary flow. After infusion, however, many of these changes are readily reversed. The decrease in 2,3-DPG, for example, results in a left shift in the Hgb-oxygen dissociation curve, but 2,3-DPG levels begin to recover within minutes and are fully restored within 24 hours.15 Further complicating the issue, the relationship between overall oxygen transport and oxygen delivery to tissues is complex. Depletion of S-nitrosohemoglobin during storage, for example, alters oxygen-dependent regulation of microcirculatory blood flow (“hypoxic vasodilation”).16 Research and debate are ongoing with regard to whether and when these and other changes are clinically significant, and how they might be addressed.17–20
Additional well-established changes in stored blood include cell leakage of potassium, although the amount (approximately 6 mEq/U) is readily tolerated by most otherwise healthy patients. PRBCs contain essentially no functional platelets or granulocytes.21
Blood Typing
ABO grouping requires that the recipient’s red cells be tested with anti-A and anti-B serum and that his or her serum be tested with A and B red cells. At about 6 months of age, patients form antibodies against the A and B antigens they lack. Those with type AB blood form no ABO group antibodies. Patients with type O have antibodies against both. The major clinically significant Rh antigen is the D antigen. Rh typing is usually done by adding a commercial reagent (anti-D) to recipient RBCs.12
The antibody screen identifies unexpected antibodies in the patient’s serum. These result from prior exposure to foreign RBC antigens during allogenic transfusion or pregnancy. The antibody screen entails mixing commercial RBC reagents (mixtures of red cells expressing clinically significant antigens) with the patient’s serum. The incidence of these unexpected antibodies in the general population is low (<1-2%), but a positive screen prompts further compatibility testing, which can take hours to days. When transfusion is delayed by a positive antibody screen in a critically ill patient, clinicians should communicate directly with the blood bank to determine the best course of action. Although ABO compatibility is mandatory in all patients, non-ABO antigens are very unlikely to cause immediate intravascular hemolysis.15,21,22 Administering blood that is not completely crossmatched is therefore an option if the need is emergent.
The traditional crossmatch requires mixing recipient serum with donor RBCs and observing for agglutination as a final compatibility test before transfusion. If the antibody screen is negative, an “immediate spin crossmatch” at room temperature serves as a final check for ABO incompatibility. A “complete crossmatch” is generally done before transfusion if the antibody screen is positive. This requires incubation to 37° C and the addition of antihuman globulin (Coombs’ reagent) to promote agglutination.13 Many blood banks also substitute a “computer crossmatch” for patients whose blood has been tested at least twice within their system. Decisions about which method is used, however, are generally made by the blood bank, not the clinician.
Special Clinical Circumstances
Administering Blood before Completion of Compatibility Testing
Full compatibility testing takes time. An antibody screen and immediate spin crossmatch at a minimum take approximately 45 to 60 minutes. This assumes a negative antibody screen followed by an immediate spin crossmatch performed at room temperature. If the antibody screen is positive, the antibody is identified via more elaborate procedures, and a complete crossmatch (using a Coombs test with incubated serum) is required. This process can take up to several hours (or even days),21 an unacceptable delay in some emergent situations.
Universal (group O) blood is used when RBCs are needed in hemorrhaging, unstable patients before any testing can be done.23,24 Female patients receive O-negative blood to prevent hemolytic disease of the newborn unless there is no chance of subsequent pregnancy. All others receive O-positive blood, because even if sensitization occurs, Rh antibodies generally do not fix complement and therefore would be unlikely to cause an acute intravascular hemolytic reaction in the unlikely event that an Rh-negative recipient twice received emergent transfusion of Rh-positive blood. Conversely, the “universal” type for fresh frozen plasma (FFP) is type AB, which contains no antibodies to either A or B antigens.
Massive Transfusion
Massive transfusion has no formal definition. Administration of at least 10 units of RBCs in 24 hours is a commonly used cutoff.25 Although patients receiving any amount of blood are susceptible to a variety of infectious, physiologic, and immunologic insults, this section will discuss those uniquely associated with massive transfusion.
Some of these complications are well understood and easily managed. Hypothermia is common in these patients, and can reduce clotting factor activity.26 Warmed intravenous fluids, blood warmers, and warming lights and blankets are often needed. Frequent laboratory testing will identify electrolyte disturbances (low magnesium and calcium, and both high and low potassium), which are in general treated in a standard fashion by replenishing deficits, or administering calcium for hyperkalemia. Acidosis is a common finding with massive hemorrhage but can also be caused by hypoperfusion, and the contribution of transfused blood to acidosis is felt to be variable. Citrate from banked blood, for example, is metabolized in the liver to bicarbonate, which can sometimes result in metabolic alkalosis. With rapid infusion or reduced hepatic function, however, this pathway can be overwhelmed, and the net effect of infusing large amounts of citrate can be worsening metabolic acidosis. A rational response to metabolic acidosis is to optimize oxygen delivery and ventilation. Administering sodium bicarbonate may be considered in severe cases, but the benefits are less certain.27
Patients receiving massive transfusion are also prone to coagulopathy and thrombocytopenia. Consumption and dilution of clotting factors and platelets occur in these patients owing to ongoing hemorrhage, fluid boluses, and transfusion of PRBCs. This undoubtedly plays a role in the coagulopathy of trauma, but recent research asserts that coagulopathy often occurs in massive trauma even before these mechanisms have taken effect.28–30 A number of reports (none of them from randomized prospective trials) have stated that a more proactive approach to administering plasma and platelets in massive transfusion is associated with better outcomes.31–43 In response, many institutions have adopted massive transfusion protocols that call for plasma (and often platelets) to be given in a 1 : 1 ratio with RBCs.44 When set ratios are not used, clinical assessment and judgment often augment laboratory values such as international normalized ratio (INR), partial thromboplastin time (PTT), and fibrinogen and platelet counts because there is no direct evidence supporting any particular threshold for platelet or coagulation factor replacement in patients with severe hemorrhage.7 Commonly recommended goals in this setting would be to consider maintaining an INR below 1.5, a fibrinogen level greater than 1 to 2 g/L, and platelet count above 50,000 to 100,000/µL.7,45
Management
A review of relevant literature supports the recent trend toward more conservative red cell transfusion triggers but also highlights the need for further investigation.46 The same can be said for FFP and other blood components.47,48 Benefits of transfusion have been difficult to prove,9 and the list of known and suspected associated risks is long and growing.49
Whole Blood
Intriguing reports on the use of fresh whole blood in military field hospitals have been published,50,51 but in civilian practice in the United States, it is generally unavailable and rarely used.
Packed Red Blood Cells
PRBCs are indicated only to improve oxygen delivery to tissues at the microvascular level and thus improve intracellular oxygen consumption. It bears repeating that demonstration of the efficacy of red cells for this purpose (or improved clinical outcomes) has proven elusive.52–54 A definitive randomized prospective study in which RBCs are withheld completely from one treatment group is unlikely to be done at this point. For decades, transfusion of RBCs was guided by the so-called “10/30 rule”: transfusion was indicated for an Hgb of less than 10 g/dL or a hematocrit of less than 30%. This practice is outdated. The largest published randomized trial in adult patients to date, the TRICC (Transfusion Requirements in Critical Care) trial, demonstrated that in the critical care setting, a transfusion threshold of 7 g/dL was as safe as a threshold of 10 g/dL.55 In this trial there was some concern that a higher trigger was more appropriate in patients with coronary artery disease (CAD).56 The FOCUS trial (Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) addresses this specific population, and results support a restrictive 8 g/dL trigger for red cell transfusion in these patients as well.57,58
Absent further research, the recommendations of the American Society of Anesthesiologists seem reasonable: transfusion is rarely needed with an Hgb concentration greater than 10 g/dL and is usually needed when the Hgb is less than 6 g/dL. Patients with an Hgb of 6 to 10 mg/dL require careful clinical judgment. Guidelines published in 2009 by the Eastern Association for the Surgery of Trauma and the American College of Critical Care Medicine and based on a thorough review of the available evidence likewise support this conservative strategy, advocating a cutoff of Hgb below 7 g/dL for most stable patients.3 Lastly, most emergency physicians would still transfuse any patient with ongoing severe hemorrhage and unstable vital signs despite adequate fluid resuscitation and would occasionally consider withholding transfusion for Hgb levels even lower than 6 g/dL in a young, healthy, asymptomatic patient at low risk for further bleeding. Another interesting area of investigation is the use physiologic transfusion triggers (such as lactate or mixed venous oxygen saturation), but further research is needed.10
Artificial Oxygen Carriers
Research into both Hgb-based oxygen carriers and perfluorocarbon emulsions is ongoing,59,60 but as yet none are approved for general clinical use in the United States. Several problems remain unsolved. Hgb-based carriers, for example, have been found to cause vasoconstriction through nitric oxide (NO) scavenging, endothelin release, and peripheral alpha-adrenergic receptor sensitization. Perfluorocarbon emulsions require relatively high partial pressure of oxygen (PO2) levels. When these emulsions are used clinically, pure oxygen is usually administered as well. It appears unlikely that artificial oxygen carriers will come into widespread emergency department (ED) use anytime soon.
Fresh Frozen Plasma
As noted previously, evidence from retrospective trials supports increased use of FFP in patients undergoing massive transfusion. This should not be generalized to all patients receiving transfusion, however. A retrospective case-control trial of 1716 transfused trauma patients receiving fewer than 10 units of blood found that administration of FFP was associated with no survival benefit, yet with a higher risk of complications, including acute respiratory distress syndrome (ARDS), pneumonia, sepsis, and multiple organ dysfunction.43 As with RBCs, indications for FFP are based primarily on observational trials and expert opinion.48,61 The following indications seem reasonable based on current evidence: coagulopathy of trauma, hemorrhaging patients with coagulopathy resulting from hepatic dysfunction or disseminated intravascular coagulation (DIC), plasma exchange for thrombotic thrombocytopenic purpura (TTP), and emergency reversal of a vitamin K antagonist in the presence of clinically significant hemorrhage.61 Because of the volume of FFP needed to reverse coagulopathy caused by vitamin K antagonism (at least 10 mL/kg, and perhaps as much as 30 mL/kg),62 however, some guidelines call for the use of prothrombin complex concentrate or recombinant factor VIIa instead, although neither is currently approved by the U.S. Food and Drug Administration (FDA) for this indication in the United States.63 FFP is not indicated for volume expansion, nonurgent reversal of a vitamin K antagonist, or treatment for abnormal INR from any cause in the absence of bleeding. Likewise, limited available evidence fails to support the use of FFP in patients with an elevated INR before invasive procedures such as central line placement and lumbar puncture, although it is common practice to administer FFP for an INR greater than 1.5 to 2.0.12,64 One problem has been that the INR often proves poorly predictive of clinical bleeding. Thromboelastography, an old technology attracting renewed interest, may prove useful in guiding coagulation therapy but is not now widely used in the ED setting.65 A full description is beyond the scope of this chapter, but this test provides information on function of both platelets and coagulation factors (including fibrinogen).
Platelets
Platelet transfusion is indicated prophylactically when the count is less than 10,000/µL, and this includes a margin of safety, as it appears that hemostasis is well maintained even at counts of 5000/µL (a threshold sometimes used for stable, afebrile inpatients). Platelets are often given to adults in a dose of 6 units of platelet concentrate (a “six-pack” of platelets), which typically raises the platelet count about 40,000 to 60,000/µL. Once again, however, this practice is not evidence based.66 Because hemostasis is maintained with platelet counts as low as 5000/µL, it seems likely that smaller, more frequent platelet transfusions should be equally efficacious, but more cost-effective, particularly in hospitalized patients. This practice is supported by a randomized trial that enrolled nearly 1300 patients undergoing prophylactic platelet transfusion, which demonstrated no increase in bleeding complications with use of a low, medium, or high dose of platelets (amounts corresponding to roughly 2, 4, or 6 units of platelet concentrate).67 This may be impractical in outpatients, in whom increasing the frequency of transfusion can be more of a burden, and discussion with the patient’s hematologist is often helpful. There are no large randomized trials on which to base recommendations for the use of prophylactic platelet transfusion before invasive bedside procedures such as lumbar puncture or central line placement. Retrospective data support the safety of performing lumbar puncture with platelet counts as low as 10,000/µL.68,69 For central line placement, a platelet count of 20,000 to 30,000/µL is generally considered adequate, and for major surgery, a count of 50,000/µL is generally acceptable, although higher cutoffs (70,000-100,000/µL) are often used for neurosurgical and retinal procedures.12,70 Another interesting consideration is whether a patient is anemic. Red cells tend to push platelets to the periphery of the vessel, where they are needed to patch endothelial disruptions. Patients with anemia appear more prone to bleeding.71 Lastly, when thrombocytopenia results from immune-mediated platelet destruction caused by idiopathic thrombocytopenic purpura (ITP) or TTP, transfusion is generally ineffective. If, however, immune-mediated destruction is a result of human leukocyte antigen (HLA) sensitization from prior transfusions, then HLA-matched single-donor platelets collected with apheresis methods may be helpful.13 Consultation with a hematologist is advisable in such cases.
Autotransfusion
Autotransfusion may be used in the emergency setting in the event of severe chest trauma. This strategy has numerous advantages: immediate availability, blood compatibility, elimination of donor-to-patient disease transmission, avoidance of the storage lesion, lower risk of circulatory overload, and fewer direct complications (e.g., hyperkalemia, hypothermia, hypocalcemia, and metabolic acidosis). It is also more acceptable to patients whose religious convictions prohibit transfusions.72 It is impractical in some settings, however, because of the limited number of appropriate trauma patients, the training required to operate the equipment, and the time required for equipment setup.73
Therapeutic Modalities
In acute hemorrhage, PRBCs are used to supplement initial crystalloid replacement. In an average adult, 1 unit (450 mL) of PRBCs increases the Hgb by about 1 g/dL or the hematocrit by about 3%.74 A similar increase in pediatric patients is obtained by administering 10 mL/kg. PRBCs are run through a filter with a large-bore intravenous line with normal saline. Lactated Ringer’s solution can lead to clotting secondary to the added calcium, and hemolysis may result with a hypotonic solution. Medications should not be added to the unit or pushed through the transfusion line unless it has been thoroughly flushed. Most transfusions are given over 60 to 90 minutes (never longer than 4 hours). Unused blood should be returned promptly to the blood bank. Any units unrefrigerated for more than 30 minutes are discarded.12
Fresh Frozen Plasma
A unit of FFP contains all clotting factors and typically has a volume of 200 to 250 mL. It must be ABO compatible and is given through blood tubing. FFP can be used to replace the most labile components (factors V and VIII), but it is given within 24 hours of thawing. An alternative product, referred to as “thawed plasma,” contains the vitamin K–dependent factors, which are stable for up to 5 days after thawing.12 One unit of activity for any coagulation factor is equal to the clotting activity found in 1 mL of FFP. As noted previously, appropriate dosage is not well grounded in evidence from clinical trials. In massive transfusion, many centers now use FFP in a 1 : 1 ratio with red cells. For other indications it seems reasonable to start with infusions of 10 to 30 mL/kg, realizing that results will be somewhat unpredictable and follow-up laboratory and clinical assessment will be necessary.12
Platelets
Crossmatching is generally unnecessary, but Rh-negative patients are treated with Rh-negative platelets because there may be enough red cells in the platelet concentrate to cause Rh sensitization. In adults the traditional dose has been 4 to 6 units (a “six-pack” of platelets), and in children it is 1 U/10 kg body weight. As noted earlier, however, use of smaller, more frequent transfusions is considered in patients who are being admitted. In frequently transfused patients, it is often desirable to reduce HLA sensitization with leukoreduced platelets.13 Once sensitization has occurred and patients have developed immune-mediated platelet refractoriness, a trial of single donor (apheresis) HLA-matched or crossmatched platelets may be considered in consultation with a hematologist.13
Outcomes
Immune-Mediated Adverse Effects
Intravascular Hemolytic Transfusion Reaction.: Intravascular hemolytic transfusion reaction is the most serious transfusion reaction. It is usually the result of ABO incompatibility, most often caused by clerical error. The resulting antigen-antibody reaction leads to the intravascular destruction of transfused red cells, producing hemoglobinemia and hemoglobinuria. The onset of symptoms is immediate and may include any of the following symptoms: fever, chills, headache, nausea, vomiting, a sensation of chest restriction, severe joint or low back pain, and a burning sensation at the site of the infusion. A feeling of impending doom is often mentioned.21 Clinical effects can include hypotension, DIC, and acute tubular necrosis. Treatment includes stopping the transfusion immediately, replacing all old tubing with new, and initiating vigorous crystalloid fluid therapy. Diuretic therapy can also be used to maintain urine output at 1 to 2 mL/kg/hr. Some patients may require pressors. Blood and urine specimens are sent to the laboratory, as well as the remainder of the transfusion and the blood tubing. Detection of free Hgb (blood and urine) and a positive result of Coombs’ test on post-transfusion, but not pretransfusion, specimens confirms the diagnosis.21
Febrile Transfusion Reaction.: Febrile transfusion reaction is the most common and least serious transfusion reaction. It is defined as a 1° C or greater temperature elevation that occurs with transfusion and for which no other medical explanation is found. Reactions are believed to result from antileukocyte antibodies, most commonly as a result of prior transfusion. Treatment is symptomatic with analgesics, antipyretics, and antihistamines. The use of leukoreduced RBCs can help decrease, but not eliminate, the risk of this reaction.15,21 If a febrile reaction occurs in a first-time transfusion, it should be treated in the same way as an extravascular hemolytic reaction until proven otherwise.
Allergic Reactions (Urticaria to Anaphylaxis).: Urticaria, or hives, may occur during a transfusion without other signs or symptoms and with no serious sequelae. It is generally attributed to an allergic, antibody-mediated response to a donor’s plasma proteins. The transfusion does not need to be stopped, and treatment with an antihistamine is usually sufficient. Consider prophylactic antihistamines in patients with a history of this reaction. Occasionally, full anaphylaxis may be caused by an anti–immunoglobulin A (IgA) reaction to IgA in the donor’s blood components. The patient is likely to have a genetic IgA deficiency. Presentation is similar to anaphylactic reactions from other causes. Treatment is with epinephrine and corticosteroids. Use of washed RBCs, and plasma products from IgA-deficient individuals can be used to avoid recurrence with subsequent transfusions.15
Transfusion-Related Acute Lung Injury.: Transfusion-related acute lung injury (TRALI) is now considered the leading cause of transfusion-related mortality.12 It has been defined as new acute lung injury (ALI) resulting in bilateral pulmonary edema and hypoxemia (ratio of arterial oxygen concentration to fraction of inspired oxygen [PaO2/FIO2] ≤300, or oxygen saturation as measured by pulse oximetry <90% on room air) and occurring during or within 6 hours after a transfusion without temporal relationship to an alternative explanation for ALI. If an alternative explanation is also present, the diagnosis of possible TRALI is appropriate.75 Implicated blood components include PRBCs, FFP, platelets, and cryoprecipitate. The initial clinical presentation is that of a noncardiogenic pulmonary edema, with dyspnea, hypoxemia, and bilateral infiltrates on chest radiograph. Fever, hypotension, and transient leukopenia may also be seen. The underlying pathophysiologic mechanism is a subject of continuing debate and could involve multiple insults.76 Proposed theories include a reaction between transfused antibodies and leukocytes in the recipient, as well as the effects of biologically active factors that accumulate in stored blood, such as cytokines and lipids.77 One strategy suggested for reducing TRALI has been to use only male donors for plasma in order to avoid allotypic leukocyte antibodies, which can occur in women as a result of prior pregnancies, or to screen for these antibodies and exclude donors when the antibodies are found.78–80 Appropriate treatment consists of stopping the transfusion, notifying the blood bank, and providing respiratory support, which may include intubation and mechanical ventilation. It is safe to continue transfusion of blood products from a different donor, if necessary. Complete resolution is usually seen within 48 to 96 hours. Overall prognosis is better than would be expected with many other causes of ALI, with a reported mortality rate of 6% in one series.81 Survivors rarely show long-term adverse effects.81
Delayed
Extravascular Hemolytic Transfusion Reaction.: Extravascular hemolytic transfusion reactions result from a non–ABO-mediated immune reaction, most often caused by an anamnestic response in a patient previously sensitized to red cell antigens by transfusion, pregnancy, or transplant. This prior exposure may result in antibody levels that are too low to detect with the antibody screen. After repeat exposure from transfusion, however, antibody levels rise, and extravascular hemolysis occurs days to weeks later. Less commonly, primary alloimmunization can occur after transfusion. The patient may have fever, anemia, and jaundice. Symptoms are not usually severe, but rare cases of oliguria or DIC do occur. Because the hemolysis is extravascular, hemoglobinemia and hemoglobinuria are generally absent.15
Transfusion-Associated Graft-versus-Host Disease.: A rare but life-threatening complication, transfusion-associated graft-versus-host disease results when transfused lymphocytes proliferate and attack the recipient. Mortality is greater than 90%. Cell-mediated immunodeficiency puts patients at risk, as does having an HLA type that is identical between donor and recipient (most often among first-degree relatives). Symptoms, which begin 3 to 30 days after transfusion, include fever, erythematous skin rash, diarrhea, elevated liver enzymes, and pancytopenia. The only effective treatment is bone marrow transplant, and most deaths result from coagulopathy or infection. Efforts are therefore directed at prevention by using gamma irradiation of all cellular components, which renders the donor lymphocytes incapable of proliferating. The use of leukocyte-poor components is also advocated. This condition should be kept in mind when transfusion is being considered for anemic leukemia or lymphoma patients, especially those who have recently received chemotherapy.15
Non–Immune-Mediated Adverse Effects
Circulatory Overload.: Chronically anemic, normovolemic elderly patients are at greatest risk for developing congestive heart failure with the rapid infusion of blood. Transfusing more slowly (over a period of 4 hours) and administering diuretics are useful in preventing this complication.15
Bacterial Contamination.: Bacterial contamination, most commonly with Yersinia enterocolitica (which grows well in cool, iron-rich environments), occurs in fewer than 1 per million units of stored RBCs but typically results in symptoms during the transfusion and carries a 60% mortality rate.49 The risk of bacterial contamination is greater, however, with platelets, which are stored at a higher temperature; contamination occurs as frequently as 1 per 1000 to 2000 units.49 During or after the transfusion, the patient may develop rigors, vomiting, abdominal cramps, fever, shock, renal failure, and DIC. If contamination is suspected, the transfusion should be stopped, blood cultures obtained from both the bag and the patient, and broad-spectrum antibiotics and hemodynamic support initiated.
Chronic
Risk of Transfusion-Transmitted Viruses.: Improved techniques for selecting and testing blood donors have dramatically reduced the risk of viral transmission of disease by transfusion. It is believed that the blood supply in the United States has never been safer.49 Current estimates for the risk of acquiring hepatitis C and human immunodeficiency virus (HIV) infection from transfusion are 1 in 1,000,000 to 2,000,000.82 The risk of hepatitis B infection, however, remains closer to 1 in 200,000 to 500,000.83 Cytomegalovirus (CMV) can be transmitted by blood transfusion as well, but this risk can be decreased by leukoreduction. Those at risk include recipients of allogeneic stem cell or solid-organ transplantation and neonates. CMV-negative blood products should be considered in these patients.83,84 West Nile virus briefly emerged as a risk, although one that varied considerably by geography and season.49 Transfusion-related infection with West Nile virus, however, has been virtually eliminated by the use of system-wide nucleic acid amplification testing.83
References
1. Spiess, BD. Red cell transfusions and guidelines: A work in progress. Hematol Oncol Clin North Am. 2007;21:185.
2. Rabbitts, JA, Bacon, DR, Nuttall, GA. Mayo Clinic and the origins of bloodbanking. Mayo Clin Proc. 2007;82:111.
3. Napolitano, LM, et al. Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care. Crit Care Med. 2009;37:3124.
4. Roback, JD, et al. Evidence-based practice guidelines for plasma transfusion. Transfusion. 2010;50:1227.
5. Slichter, SJ. Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program. 2007:172–178.
6. Zielinski, MD, Park, MS, Jenkins, D. Appropriate evidence-based practice guidelines for plasma transfusion would include a high ratio of plasma to red blood cells based on the available data. Transfusion. 2010;50:2762.
7. Rossaint, R, et al. Management of bleeding following major trauma: An updated European guideline. Crit Care. 2010;14:R52.
8. Cotton, BA, et al. Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications. J Trauma. 2009;66:41.
9. Marik, PE, Corwin, HL. Efficacy of red blood cell transfusion in the critically ill: A systematic review of the literature. Crit Care Med. 2008;36:2667.
10. Vallet, B, Robin, E, Lebuffe, G. Venous oxygen saturation as a physiologic transfusion trigger. Crit Care. 2010;14:213.
11. Whitaker, BI, et al. The 2007 National Blood Collection and Utilization Survey Report. http://www.hhs.gov/ash/bloodsafety/2007nbcus_survey.pdf.
12. Roback JD, Combs MR, Grossman BJH, Hillyer CD, eds. Technical Manual, 16th ed, Bethesda, Md: AABB, 2008.
13. Cushing, MM, Ness, PM. Principles of red blood cell transfusion. In Hoffman R, et al, eds.: Hematology: Basic Principles and Practice, 5th ed, Philadelphia: Churchill Livingstone, 2008.
14. Rao, SV, Califf, RM. Is old blood bad blood? Am Heart J. 2010;159:710–712.
15. Harmening, D. Modern Blood Banking and Transfusion Practices, 5th ed. Philadelphia: FA Davis; 2005.
16. Reynolds, JD, et al. S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood. Proc Natl Acad Sci U S A. 2007;104:17058.
17. Lelubre, C, Piagnerelli, M, Vincent, JL. Association between duration of storage of transfused red blood cells and morbidity and mortality in adult patients: Myth or reality? Transfusion. 2009;49:1384.
18. Shander, A, Javidroozi, M. A reductionistic approach to aged blood. Anesthesiology. 2010;113:1.
19. Lall, RN, et al. Phosphodiesterase inhibition attenuates stored blood-induced neutrophil activation: A novel adjunct to blood transfusion. J Am Coll Surg. 2006;202:10.
20. Ho, J, Sibbald, WJ, Chin-Yee, IH. Effects of storage on efficacy of red cell transfusion: When is it not safe? Crit Care Med. 2003;31:S687.
21. Despotis, GJ, Zhang, L, Lublin, DM. Transfusion risks and transfusion-related pro-inflammatory responses. Hematol Oncol Clin North Am. 2007;21:147.
22. Petz, LD. “Least incompatible” units for transfusion in autoimmune hemolytic anemia: Should we eliminate this meaningless term? A commentary for clinicians and transfusion medicine professionals. Transfusion. 2003;43:1503.
23. Dutton, RP, Shih, D, Edelman, BB, Hess, J, Scalea, TM. Safety of uncrossmatched type-O red cells for resuscitation from hemorrhagic shock. J Trauma. 2005;59:1445–1449.
24. Ball, CG. Uncrossmatched blood transfusions for trauma patients in the emergency department: Incidence, outcomes and recommendations. Can J Surg. 2011;54:111–115.
25. Sihler, KC, Napolitano, LM. Massive transfusion: New insights. Chest. 2009;136:1654.
26. DeLoughery, TG. Coagulation defects in trauma patients: Etiology, recognition, and therapy. Crit Care Clin. 2004;20:13–24.
27. Forsythe, SM, Schmidt, GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest. 2000;117:260.
28. Brohi, K. Trauma induced coagulopathy. J R Army Med Corps. 2009;155:320.
29. Frith, D, Brohi, K. The acute coagulopathy of trauma shock: Clinical relevance. Surgeon. 2010;8:159.
30. Frith, D, et al. Definition and drivers of acute traumatic coagulopathy: Clinical and experimental investigations. J Thromb Haemost. 2010;8:1919.
31. Phan, HH, Wisner, DH. Should we increase the ratio of plasma/platelets to red blood cells in massive transfusion: What is the evidence? Vox Sang. 2010;98:395.
32. Borgman, MA, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007;63:805.
33. Dente, CJ, et al. Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center. J Trauma. 2009;66:1616.
34. Duchesne, JC, et al. Review of current blood transfusions strategies in a mature level I trauma center: Were we wrong for the last 60 years? J Trauma. 2008;65:272.
35. Gunter, OL, Jr., et al. Optimizing outcomes in damage control resuscitation: Identifying blood product ratios associated with improved survival. J Trauma. 2008;65:527.
36. Holcomb, JB, et al. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg. 2008;248:447.
37. Kashuk, JL, et al. Postinjury life threatening coagulopathy: Is 1:1 fresh frozen plasma:packed red blood cells the answer? J Trauma. 2008;65:261.
38. Maegele, M, et al. Red-blood-cell to plasma ratios transfused during massive transfusion are associated with mortality in severe multiple injury: A retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft fur Unfallchirurgie. Vox Sang. 2008;95:112.
39. Perkins, JG, et al. An evaluation of the impact of apheresis platelets used in the setting of massively transfused trauma patients. J Trauma. 2009;66:S77.
40. Riskin, DJ, et al. Massive transfusion protocols: The role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg. 2009;209:198.
41. Sperry, JL, et al. An FFP:PRBC transfusion ratio >/=1:1.5 is associated with a lower risk of mortality after massive transfusion. J Trauma. 2008;65:986.
42. Teixeira, PG, et al. Impact of plasma transfusion in massively transfused trauma patients. J Trauma. 2009;66:693.
43. Inaba, K, et al. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg. 2010;210:957.
44. Schuster, KM, et al. The status of massive transfusion protocols in United States trauma centers: Massive transfusion or massive confusion? Transfusion. 2010;50:1545.
45. Thomas, D, et al. Blood transfusion and the anaesthetist: Management of massive haemorrhage. Anaesthesia. 2010;65:1153.
46. Carless, PA, et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 10, 2010.
47. Oeyen, S. Fresh frozen plasma transfusion in the critically ill: Yes, no, or maybe? Crit Care Med. 2007;35:1777.
48. Stanworth, SJ, et al. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol. 2004;126:139.
49. Goodnough, LT. Risks of blood transfusion. Anesthesiol Clin North America. 2005;23:241.
50. Spinella, PC, et al. Risks associated with fresh whole blood and red blood cell transfusions in a combat support hospital. Crit Care Med. 2007;35:2576.
51. Spinella, PC, et al. Fresh whole blood transfusions in coalition military, foreign national, and enemy combatant patients during Operation Iraqi Freedom at a U.S. combat support hospital. World J Surg. 2008;32:2.
52. Hébert, PC, Van der Linden, P, Biro, G, Hu, LQ. Physiologic aspects of anemia. Crit Care Clin. 2004;20:187–212.
53. Sakr, Y, et al. Microvascular response to red blood cell transfusion in patients with severe sepsis. Crit Care Med. 2007;35:1639.
54. Vamvakas, EC, Blajchman, MA. Blood still kills: Six strategies to further reduce allogeneic blood transfusion–related mortality. Transfus Med Rev. 2010;24:77.
55. Hébert, PC, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409.
56. Wu, WC, et al. Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med. 2001;345:1230.
57. Carson, JL, et al. Transfusion triggers: A systematic review of the literature. Transfus Med Rev. 2002;16:187.
58. Carson, JL, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453–2462.
59. Mackenzie, CF, et al. When blood is not an option: Factors affecting survival after the use of a hemoglobin-based oxygen carrier in 54 patients with life-threatening anemia. Anesth Analg. 2010;110:685.
60. Cabrales, P, Carlos Briceno, J. Delaying blood transfusion in experimental acute anemia with a perfluorocarbon emulsion. Anesthesiology. 2011;114:901.
61. Pinkerton, PH, Callum, JL. Rationalizing the clinical use of frozen plasma. CMAJ. 2010;182:1019.
62. Chowdhury, P, et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol. 2004;125:69.
63. Ansell, J, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S.
64. Stanworth, SJ, Walsh, TS. Fresh frozen plasma: Friend or faux pas in critical illness? Crit Care Med. 2005;33:2714.
65. Chen, A, Teruya, J. Global hemostasis testing thromboelastography: Old technology, new applications. Clin Lab Med. 2009;29:391.
66. Slichter, SJ. Platelet transfusion therapy. Hematol Oncol Clin North Am. 2007;21:697.
67. Slichter, SJ, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med. 2010;362:600.
68. Howard, SC, et al. Safety of lumbar puncture for children with acute lymphoblastic leukemia and thrombocytopenia. JAMA. 2000;284:2222.
69. Vavricka, SR, et al. Safety of lumbar puncture for adults with acute leukemia and restrictive prophylactic platelet transfusion. Ann Hematol. 2003;82:570.
70. Babic, A. Principles of platelet transfusion therapy. In Hoffman R, et al, eds.: Hematology: Basic Principles and Practice, 5th ed, Philadelphia: Churchill Livingstone, 2008.
71. Valeri, CR, et al. Anemia-induced increase in the bleeding time: Implications for treatment of nonsurgical blood loss. Transfusion. 2001;41:977.
72. Kulvatuny, N, Heard, SO. Care of the injured Jehovah’s Witness patient: Case report and review of the literature. J Clin Anesth. 2004;16:548–553.
73. Pena, ME, Irvin, CB. Autotransfusion. In Roberts JR, Hedges JR, eds.: Clinical Procedures in Emergency Medicine, 5th ed, Philadelphia: Saunders, 2010.
74. Armas-Loughran, B, Kalra, R, Carson, JL. Evaluation and management of anemia and bleeding disorders in surgical patients. Med Clin North Am. 2003;87:229.
75. Kleinman, S, et al. Toward an understanding of transfusion-related acute lung injury: Statement of a consensus panel. Transfusion. 2004;44:1774.
76. Marik, PE, Corwin, HL. Acute lung injury following blood transfusion: Expanding the definition. Crit Care Med. 2008;36:3080.
77. Sheppard, CA, et al. Transfusion-related acute lung injury. Hematol Oncol Clin North Am. 2007;21:163.
78. Eder, AF, et al. Effective reduction of transfusion-related acute lung injury risk with male-predominant plasma strategy in the American Red Cross (2006-2008). Transfusion. 2010;50:1732.
79. Wright, SE, et al. Acute lung injury after ruptured abdominal aortic aneurysm repair: The effect of excluding donations from females from the production of fresh frozen plasma. Crit Care Med. 2008;36:1796.
80. Vlaar, AP, et al. The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: A prospective nested case-control study. Blood. 2011;117:4218.
81. Looney, MR. Transfusion-related acute lung injury: A review. Chest. 2004;126:249–258.
82. Zou, S, et al. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion. 2010;50:1495.
83. Stramer, SL. Current risks of transfusion-transmitted agents: A review. Arch Pathol Lab Med. 2007;131:702.
84. Mintz, PD. Transfusion Therapy: Clinical Principles and Practice, 2nd ed. Bethesda, Md: American Association of Blood Banks; 2005.
