Each year in the United States, nearly 21 million blood components are transfused to approximately 4.5 million patients.1, 2 Many patients will require immediate transfusion of one or more units of blood or blood products for life-threatening situations or to prevent clinical deterioration. Patients injured in motor vehicle accidents often require upward of 50 units of blood products during the initial resuscitative period, while patients sustaining acute burn injuries may require up to 20 units of platelets.2 Since the supply of blood products can be rapidly depleted, all blood components must be used judiciously.
Despite the numerous benefits of transfusion, the potential for both short- and long-term adverse reactions is significant. Allogeneic transfusions (those of human blood products) may be complicated by incompatibility of donor and recipient. Such hemolytic, or “classic,” transfusion reactions represent only one potential complication associated with transfusion therapy. Others include infection, immunosuppression, volume overload, and adverse reactions to the chemicals used in the preparation and storage of blood products.3-6
The approach to transfusion therapy has evolved over the years, based on targeted studies that examined the thresholds at which the benefits of administering whole blood or blood products outweigh the risks. When transfusion is anticipated or administered, nursing responsibilities include risk assessment and continuous monitoring for changes in patient status. Nurses need to understand current best practices in the administration of blood products, the appropriate uses of blood products, and the potential for both immediate and delayed reactions, especially in patients who receive frequent or multiple transfusions. This article reviews the blood products that are commonly transfused, discusses the signs and symptoms associated with potential complications of transfusion, and examines current recommendations for transfusion therapy that are widely supported in the medical and nursing literature.
WHOLE BLOOD AND BLOOD PRODUCTS
The decision to transfuse whole blood or selected blood components is based on the patient's condition and the circumstances necessitating therapy. Depending on the blood product administered, transfusion can be used to restore oxygen-carrying capacity, replenish intravascular volume, or prevent or control hemorrhage.
Fresh whole blood is commonly transfused in military settings and disaster or mass casualty events in which hemorrhage may be common and blood components that address trauma-related coagulopathy may be scarce. Its use in civilian care, however, fell out of favor shortly after World War II with the availability of blood components, which offer the following advantages7, 8:
- safe storage for longer periods
- the ability to target specific patient needs
- a reduced risk of infection and other complications
Nevertheless, whole blood, which is collected and stored in an anticoagulant-preservative solution, is the common starting product for component isolation and modification for transfusion. After platelets are isolated from red blood cells in whole blood, the red blood cells are stored at 1°C to 6°C to extend their posttransfusion survivability.9 For the purpose of transfusion therapy, there are four different components within whole blood—red blood cells, plasma, cryoprecipitate, and platelets—each of which can be modified to help achieve goal-directed outcomes while mitigating the risk of adverse effects.
Packed red blood cells are the most commonly transfused of all blood products.10 Composed primarily of hemoglobin, packed red blood cells are used to treat acute and chronic anemias that are not caused by deficiencies in iron, vitamin B12, folic acid, or erythropoietin. Transfusion of packed red blood cells increases oxygen-carrying capacity and restores blood volume. Packed red blood cells can be prepared from whole blood through centrifugation or apheresis, in which the plasma is separated from the cellular components of blood and the unused product is returned to the donor.11 The cells are packed with additive solutions containing varying concentrations of dextrose, adenine, sodium phosphate, mannitol, sodium bicarbonate, sodium chloride, sodium citrate, or citric acid and can be prepared in ways that limit the risk of transfusion reactions.11
Leukoreduction, or the reduction of white blood cells contained in a unit of packed red blood cells to a threshold below 5 × 106 in accordance with the standards of the AABB (formerly known as the American Association of Blood Banks),11 is commonly used to reduce such risks as viral transmission, febrile nonhemolytic transfusion reaction, human leukocyte antigen (HLA) alloimmunization, and platelet refractoriness, especially in patients who are immunosuppressed or who require multiple transfusions.12 Further investigation is required to determine the effectiveness of this strategy in reducing such adverse transfusion reactions.13
Low-volume packed red blood cells may be used to treat patients who have low cardiac output, such as those with heart failure. Such patients need hemoglobin but cannot tolerate excessive volume. The definition of “low-volume” transfusion varies across studies14-17; we define low volume as the reduction of total blood product volume administered.
Fresh frozen plasma contains albumin, multiple coagulation factors, fibrinolytic proteins, and immunoglobulin. Fresh frozen plasma contributes to volume expansion because the proteins it contains can pull fluid from the extracellular space back into the vessels through an oncotic pressure gradient. However, it should not be transfused primarily for this purpose; rather, it is used to treat coagulation deficiencies.11 Plasma contains all the coagulation factors, which is an important consideration for certain subpopulations requiring emergency care, such as patients with trauma-associated coagulopathy, massive hemorrhage, or complications from anticoagulant therapy. Plasma is frozen at a temperature of −18°C or colder within 24 hours of collection.11 It normally requires 40 minutes for thawing and pooling in the blood bank before it can be issued. Once plasma has been thawed, it must be transfused within 24 hours of preparation or discarded.
Cryoprecipitate is prepared from fresh frozen plasma thawed to 1°C to 6°C; the cold-insoluble precipitate is recovered after centrifugation.11 This product, which contains concentrates of factor VIII, fibrinogen, factor XIII, von Willebrand factor, and fibronectin, is used to treat fibrinogen deficiency and to control bleeding in hemophilia or other coagulation deficiencies. Cryoprecipitate is seldom used in emergency care, but may be considered for patients presenting with bleeding secondary to these deficits. Cryoprecipitate normally requires 40 minutes for thawing and pooling in the blood bank before issue and must be infused within four hours of pooling.
Platelets are used to replenish low platelet counts or to treat platelet dysfunction. The goal of platelet transfusion is to provide enough normally functioning platelets to facilitate platelet aggregation and clot formation. Platelets are either derived from whole blood or prepared by apheresis and suspended in plasma. Of note, the method of preparation affects the concentration of platelets. Whereas a unit derived from whole blood contains at least 5.5 × 1010 platelets, a unit prepared by apheresis contains at least 3 × 1011. For this reason, the therapeutic adult dose of at least 3 × 1011 is ordered as either one unit of apheresis platelets derived from a single donor or four to six units of pooled platelets derived from the whole blood of multiple donors (commonly called a “four pack” or a “six pack”).11 Since apheresis platelets are obtained from a single donor, their use reduces the recipient's risk of alloimmunity.
TYPING AND COMPATIBILITY
Two classification systems are commonly used to determine compatibility between donor blood products and transfusion recipients: ABO and D antigen typing. ABO typing identifies the antigen that resides on a person's red blood cell membranes; circulating antibodies to the opposing blood type are found in this person's plasma. In other words, people with type A antigens on their red blood cell membranes will have type B antibodies in their plasma, which will react to a transfusion of type B red blood cells; those with type B antigens on their red blood cell membranes will have type A antibodies in their plasma, which will react to a transfusion of type A red blood cells. People with type O blood express neither A antigens nor B antigens on their red blood cells. Conversely, people with type AB blood have both A and B antigens on their red blood cell membranes but no A or B antibodies in their plasma.
The D antigen, or Rh, classification system, initially named for an erroneous association with the Rhesus monkey species, identifies an antibody response to the D antigen, which is also located on the red blood cell membrane. The D antigen triggers an aggressive immunologic response, such as the fatal hemolytic reaction that can occur in the pregnancies of an Rh-negative (D antigen–negative) mother previously exposed to a D antigen–positive fetus. Unless steps are taken to prevent Rh (D antigen) alloimmunization, such as the timely administration of Rho(D) immune globulin, D antigen–positive fetuses in subsequent pregnancies would be vulnerable to attack by maternal D antibodies.
Patients who may require transfusion therapy should have their serum typed and screened to determine ABO and D antigen classification, as well as the presence of other infectious or allergenic antibodies. The final phase of donor–recipient compatibility testing is a crossmatch in which a portion of the donor blood product is combined with a sample of the recipient's blood. If agglutination occurs, it indicates incompatibility.
COMPLICATIONS OF TRANSFUSION THERAPY
As with any therapy, transfusion is associated with a risk of complications (see Table 13, 6, 11, 18-27). There are two broad categories of complications: acute and delayed. Acute transfusion reactions are defined in the Serious Hazards of Transfusion (SHOT) reporting categories as allergic or febrile transfusion reactions occurring within 24 hours of blood component transfusion.28 These include acute hemolytic transfusion reactions, febrile nonhemolytic transfusion reactions, allergic and anaphylactic reactions, transfusion-associated circulatory overload (TACO), and transfusion-related acute lung injury (TRALI). Delayed transfusion reactions of varying severity may occur days to years after transfusion. These include delayed hemolytic reactions, transfusion-associated graft versus host disease (TA-GVHD), posttransfusion purpura, and transfusion-related immunomodulation (TRIM).19, 29, 30 Nurses need to be able to identify patients at risk for acute as well as delayed complications, thereby improving surveillance along the entire trajectory of care.
ACUTE TRANSFUSION REACTIONS
Acute hemolytic transfusion reactions are caused by incompatibility of antigens on transfused red blood cells and antibodies in the recipient's plasma.11 The identification errors responsible for such reactions may occur during crossmatching or during pretransfusion identification of the patient and the product. The reaction may be signaled by a rise in temperature and heart rate, chills, dyspnea, chest or back pain, and abnormal bleeding or shock.11
In response to any acute transfusion reaction, nurses need to take the following immediate actions:
- Stop the transfusion.
- Notify the ordering provider.
- Send the remaining blood component to the blood bank for analysis.
- Maintain a patent iv line with normal saline for potential emergency intervention.
- Reassess the patient every five to 15 minutes, observing for signs of coagulopathy and renal failure.
Although hemolytic reactions can be devastating, uncrossmatched blood, including Rh-positive (D antigen–positive) blood, may be required in the setting of uncontrolled hemorrhage, when resources are depleted. In 2008, Murthi and colleagues examined the outcomes of patients treated in their trauma receiving unit with transfusions of uncrossmatched group O red cells for uncontrolled hemorrhage.31 The authors found that the benefits of transfusion often outweighed the risks of Rh incompatibility.
Febrile nonhemolytic transfusion reactions are among the more common reactions to the transfusion of packed red blood cells or platelets,23, 24 and manifest as an unexplained 1°C (1.8°F) rise in temperature during or shortly after transfusion.25 These generally mild reactions are thought to be caused by a cytokine response to antibodies directed against white blood cells in the product19 or through the actions of cytokines present in the product.25 Antipyretics can be used to treat symptoms of febrile nonhemolytic reactions.19 It is important for nursing assessments to reflect any findings that suggest the patient's response is caused by an infection.
Allergic and anaphylactic reactions range from mild urticaria or wheezing that responds to antihistamines to severe systemic reactions characterized by hypotension, tachycardia, nausea, vomiting, abdominal pain, severe dyspnea, pulmonary or laryngeal edema, or bronchospasm.11 Severe systemic reactions occur most often with the transfusion of plasma-containing components, but can occur with the transfusion of any blood product, as even packed red blood cells contain small amounts of plasma.11 Treatment includes supportive care with antihistamines, epinephrine, and, if indicated, blood pressure and ventilatory support.
In 2011, Murthi and colleagues published an update on transfusion safety in the setting of traumatic injury that addressed the practice of reconstituting blood products (packed red blood cells, plasma, and platelets) to create a “modified whole blood” that supplies the needed individual component while limiting exposure to bloodborne infectious agents.32 As the science of transfusion medicine evolves, the approach to managing massive hemorrhage will remain a topic of research, and guidelines will be revised accordingly.
TACO, the most deadly and one of the two most common adverse reactions associated with transfusion, typically occurs within six hours of blood product administration.18, 26, 27 Depending on patient characteristics, as well as the rate and volume of transfusion required, reported incidence ranges from less than 1% to 11%.3, 26, 27, 33 (See Diagnostic Criteria for TACO.20)
TACO prevention requires nurses to obtain a thorough patient history and to assess fluid volume status prior to transfusion. Patients over age 70 or under age three, those with a history of cardiogenic pulmonary edema (as indicated by an ejection fraction of less than 60% on echocardiogram or the need for daily diuretic therapy), and those with renal dysfunction should be considered at high risk. Further research is required to identify more precisely the populations at elevated risk for TACO.26 Patients who require transfusion therapy and have been determined to be at risk for TACO should receive the blood product at a slower infusion rate; if possible, only one unit of blood product should be ordered at a time and diuretic therapy should be administered.3 In addition to close hemodynamic monitoring and ongoing physical assessment, supplemental oxygen therapy and nitrates may be used to treat TACO; patients with respiratory fatigue may benefit from a trial of noninvasive positive pressure ventilation.6 Clear communication between caregivers, especially regarding the rate at which blood products are administered and appropriate diuresis, is essential when patients are at risk for TACO. Protocols and pretransfusion checklists can reduce the risk of TACO. A protocol developed by Tseng and colleagues resulted in no cases of transfusion-associated overload, and no cases of severe hypokalemia associated with the preemptive use of loop diuretics.18 TACO surveillance and early identification, combined with aggressive treatment of pulmonary edema, may prevent patient decompensation and respiratory failure. Transfusing low-volume blood products and minimizing colloid use in patients at risk is also beneficial.34
TRALI presents as an acute onset of respiratory distress, hypoxemia, and noncardiogenic pulmonary edema within six hours of transfusion.24 (See Diagnostic Criteria for TRALI.20) It typically occurs when white blood cell antibodies, proinflammatory molecules, and cytokines in blood products trigger an inflammatory cascade of granulocyte activation and degranulation, causing injury to the alveolar capillary membrane.22 Margination, or alignment of neutrophils against the endothelial walls of the capillaries, and the subsequent production of cytokines along the pulmonary endothelium are thought to be a major reason for increased capillary permeability, leading to acute lung injury.22, 35 Activation of an immune response is often caused by transfusion of donor HLA antibodies and activation of alveolar neutrophils, which elicit signs that may be confused with infection.22
Inflammatory and immune mediators may produce fever, tachycardia, hypothermia, or blood pressure instability.22 As with TACO, the diagnosis of TRALI is complicated by the underlying conditions generally seen in patients requiring transfusion, many of which may cause acute lung injury. For this reason, it's important to note trends in patient decompensation relative to the timing of the transfusion.
TRALI is usually a self-limiting process with an overall mortality rate of 5% to 10%.22 Treatment for TRALI requires aggressive respiratory support, including mechanical ventilation, applying restrictive tidal volume and possibly diuretics, fluid restriction, and extracorporeal membrane oxygenation. If the patient has a history of TRALI, the following strategies may be used to prevent subsequent incidents22:
- adopting a restrictive transfusion approach
- selecting blood components based on patient risk factors and history
- transfusing fresh blood or transfusing components to reduce antibody transmission
- washing stored cellular components to remove antibodies
DELAYED TRANSFUSION REACTIONS
Delayed hemolytic reactions can occur days to weeks after transfusion. Like acute hemolytic reactions, they are caused by incompatibility of antigens on transfused red blood cells and the antibodies in the recipient's plasma. Patients with such reactions may develop a low-grade fever and mild jaundice. Direct antiglobulin testing may be positive. Blood tests may reveal low hemoglobin levels and elevated lactate dehydrogenase. In the absence of brisk hemolysis, no treatment is required.19
TA-GVHD is seen primarily in immunocompromised patients receiving allogenic stem cell transplants. Often fatal, TA-GVHD is characterized by fever, rash, and diarrhea occurring within two weeks of transfusion, but may also present as hepatitis or marrow dysfunction. TA-GVHD may be prevented by irradiating donor lymphocytes prior to transfusion.19
Posttransfusion purpura, an immune response to platelet antigens that produces thrombocytopenia, may occur one to three weeks after transfusion. In many patients, the condition resolves spontaneously. Patients at risk for bleeding are treated with iv immunoglobulins, plasmapheresis, or platelet transfusion.19
TRIM is a response that may develop in patients receiving multiple transfusions. At this time, TRIM is not classified by specific criteria as an adverse reaction to transfusion.20 The leukocytes, soluble mediators derived from white blood cells, and HLA molecules commonly found in blood products are thought to contribute to the immunosuppression often seen following transfusion.36 Given the immunomodulating effects of critical illness, it is difficult to pinpoint the direct effects of TRIM and the timeline over which it may develop. Nurses, however, need to bear in mind that transfusion therapy is an independent risk factor for infection, morbidity, and death in critically ill patients.4 Accordingly, they need to carefully consider potential complications in anticipation of transfusion, during blood product administration, and when caring for patients who have received blood products in the past, understanding that such patients remain at risk for immune compromise and infection.
COMPLICATIONS RELATED TO PRODUCT STORAGE
Metabolic derangements may occur following transfusion but are most often associated with large-volume or massive transfusion, particularly in patients with underlying liver or kidney dysfunction.26, 37 Several of the additive solutions used to preserve and store blood products, as well as the anticoagulant solutions used for component manufacturing, contain citrate, sodium phosphate, sodium bicarbonate, mannitol, and other constituents that can contribute to metabolic alkalosis or acidosis, hypocalcemia, hypokalemia, or hyperkalemia. When patients require transfusions, nurses must provide baseline and ongoing assessments while monitoring any transfusion reactions. When patients are transferred following transfusion, communication to the receiving team should include risk factors for acute or delayed complications.
TRANSFUSION CONSIDERATIONS IN TRAUMA CARE
Traumatic injury is the leading cause of death among people ages five through 49.38 Trauma can cause rapid blood loss, reducing both oxygen-carrying capacity and cardiac output as intravascular volume decreases. In addition to the direct loss of blood through uncontrolled hemorrhage, trauma can cause patients to develop severe coagulopathy, especially in the presence of acidosis and hypothermia.39
Traditionally, hemorrhagic shock with refractory hypotension or active bleeding was treated with a two-liter infusion of a crystalloid solution, followed by a transfusion of packed red blood cells.31 The approach to transfusion therapy after traumatic injury has changed dramatically. Efforts to limit morbidity and mortality focus on early recognition of shock, implementation of massive transfusion protocols, and control of factors that may worsen coagulopathy. The primary goal in resuscitation following trauma is to control and stop the source of bleeding. However, transfusion therapy is often necessary to save lives, and nurses are essential in identifying the patients who require transfusion, reducing risks of complications, and safely administering transfusions in accordance with current recommendations.
Other considerations include availability of resources. In the setting of mass casualties or in cases in which one critically injured patient taxes the institution's supply of transfusion products, consideration must be given to strategies that benefit the greatest number of patients.40-43
THE ESSENTIAL ROLE OF NURSING IN TRANSFUSION
Nurses are essential to the success of transfusion therapy in the emergency care setting and throughout all hospital units that receive transfusion recipients. Ongoing assessment and recognition of the patient's history are important factors in determining appropriate use of blood products and in assessing patient risk of both short- and long-term complications of transfusion. Current guidelines and recommendations support the use of a more restrictive approach to replacing blood products (see Restrictive Transfusion Strategies: The TRICC Trial6, 23, 44-50), but clinical judgment is crucial in determining whether the risks associated with transfusion outweigh the patient's need for this lifesaving therapy. As with nearly all aspects of health care, the nurse's assessment and therapeutic skills are a critical component of management.
2. New York Blood Center. Donate blood: blood facts
. n.d. http://nybloodcenter.org/donate-blood/blood-facts
3. Lieberman L, et al. A retrospective review of patient factors, transfusion practices, and outcomes in patients with transfusion-associated circulatory overload Transfus Med Rev 2013 27 4 206 12
4. Muszynski JA, et al. Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness Transfusion 2017 57 1 195 206
5. Pavenski K, et al. HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management Tissue Antigens 2012 79 4 237 45
6. Roubinian NH, Murphy EL Transfusion-associated circulatory overload (TACO): prevention, management, and patient outcomes International Journal of Clinical Transfusion Medicine 2015 3 17 28
7. Goforth CW, et al. Fresh whole blood transfusion: military and civilian implications Crit Care Nurse 2016 36 3 50 7
8. Kauvar DS, et al. Fresh whole blood transfusion: a controversial military practice J Trauma 2006 61 1 181 4
9. Hillyer CD Shaz BH Component preparation and manufacturing. In: Shaz BH, et al., editors. Transfusion medicine and hemostasis: clinical and laboratory aspects.
2nd ed. Amsterdam: Elsevier Science; 2013. p. 61-7.
10. Whitaker BI, et al. The 2013 AABB blood collection, utilization, and patient blood management survey report: final
. Bethesda, MD: American Association of Blood Banks (AABB); 2015 Dec 18. http://www.aabb.org/research/hemovigilance/bloodsurvey/Documents/2013-AABB-Blood-Survey-Report.pdf
11. American Association of Blood Banks (AABB). Circular of information for the use of human blood and blood components
; 2013 Nov. http://www.aabb.org/tm/coi/Documents/coi1017.pdf
12. Sharma RR, Marwaha N Leukoreduced blood components: advantages and strategies for its implementation in developing countries Asian J Transfus Sci 2010 4 1 3 8
13. Simancas-Racines D, et al. Leukoreduction for the prevention of adverse reactions from allogeneic blood transfusion Cochrane Database Syst Rev 2015 12 CD009745
14. Baysinger K, et al. What's in the box? The effectiveness of a low-volume massive transfusion protocol Am Surg 2016 82 7 602 7
15. Hussmann B, et al. Does increased prehospital replacement volume lead to a poor clinical course and an increased mortality? A matched-pair analysis of 1896 patients of the Trauma Registry of the German Society for Trauma Surgery who were managed by an emergency doctor at the accident site Injury 2013 44 5 611 7
16. Sisak K, et al. Acute transfusion practice during trauma resuscitation: who, when, where and why? Injury 2013 44 5 581 6
17. Xi CY, et al. [Investigation and analysis of blood transfusion in 1 766 hospitalized trauma patients.] Zhongguo Shi Yan Xue Ye Xue Za Zhi 2015 23 1 228 33
18. Tseng E, et al. An order set and checklist improve physician transfusion ordering practices to mitigate the risk of transfusion-associated circulatory overload Transfus Med 2016 26 2 104 10
19. Gorgas DL, Kaide CG Roberts JR Transfusion therapy
: blood and blood products Roberts and Hedges’ clinical procedures in emergency medicine 2014 6th ed. Philadelphia Elsevier Saunders 496 517
20. Centers for Disease Control and Prevention, National Healthcare Safety Network. Biovigilance component hemovigilance module surveillance protocol
. Atlanta; 2017 Jan. Protocol vol 2.4. https://www.cdc.gov/nhsn/pdfs/biovigilance/bv-hv-protocol-current.pdf
21. Ellsworth B, et al. Adverse reaction case definition criteria: American Association of Blood Banks (AABB), editor. Bethesda, MD; 2011. http://www.aabb.org/research/hemovigilance/Documents/diagnose_full.html
22. Vlaar AP, Juffermans NP Transfusion-related acute lung injury: a clinical review Lancet 2013 382 9896 984 94
23. Carson JL, et al. Red blood cell transfusion: a clinical practice guideline from the AABB Ann Intern Med 2012 157 1 49 58
24. Sahu S, et al. Adverse events related to blood transfusion Indian J Anaesth 2014 58 5 543 51
25. Paglino JC, et al. Reduction of febrile but not allergic reactions to RBCs and platelets after conversion to universal prestorage leukoreduction Transfusion 2004 44 1 16 24
26. Alam A, et al. The prevention of transfusion-associated circulatory overload Transfus Med Rev 2013 27 2 105 12
27. Hendrickson JE, et al. Incidence of transfusion reactions: a multicenter study utilizing systematic active surveillance and expert adjudication Transfusion 2016 56 10 2587 96
28. Serious Hazards of Transfusion (SHOT). Definitions of current SHOT reporting categories and what to report
. Plymouth Grove, Manchester, UK; 2017 Apr. https://www.shotuk.org/wp-content/uploads/SHOT-Definitions-Jan-2016-1.pdf
29. Vamvakas EC, Blajchman MA Transfusion-related immunomodulation (TRIM): an update Blood Rev 2007 21 6 327 48
30. Vamvakas EC, Blajchman MA Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention Blood 2009 113 15 3406 17
31. Murthi SB, et al. Transfusion medicine in trauma patients Expert Rev Hematol 2008 1 1 99 109
32. Murthi SB, et al. Transfusion medicine in trauma patients: an update Expert Rev Hematol 2011 4 5 527 37
33. Gajic O, et al. Pulmonary edema after transfusion: how to differentiate transfusion-associated circulatory overload from transfusion-related acute lung injury Crit Care Med 2006 34 5 Suppl S109 S113
34. Andrzejewski C Jr., et al. How we view and approach transfusion-associated circulatory overload: pathogenesis, diagnosis, management, mitigation, and prevention Transfusion 2013 53 12 3037 47
35. Kim KN, et al. The usefulness of a classification and regression tree algorithm for detecting perioperative transfusion-related pulmonary complications Transfusion 2015 55 11 2582 9
36. Brand A Immunological complications of blood transfusions Presse Med 2016 45 7-8 Pt 2 e313 e324
37. Hess JR Massive blood transfusion. New York, NY: UpToDate, 2017. https://www.uptodate.com/contents/massive-blood-transfusion
38. World Health Organization. Injuries and violence: the facts 2014
. Geneva, Switzerland; 2014. http://apps.who.int/iris/bitstream/10665/149798/1/9789241508018_eng.pdf?ua=1&ua=1&ua=1
39. Gando S, Hayakawa M Pathophysiology of trauma-induced coagulopathy and management of critical bleeding requiring massive transfusion Semin Thromb Hemost 2016 42 2 155 65
40. Doughty H, et al. Mass casualty events: blood transfusion emergency preparedness across the continuum of care Transfusion 2016 56 Suppl 2 S208 S216
41. National Advisory Committee on Blood and Blood Products. Emergency framework for rationing of blood for massively bleeding patients during a red phase of a blood shortage
. Winnipeg, MB; 2012 Apr 14. http://www.nacblood.ca/resources/shortages-plan/emergency-framework-final.pdf
42. National Advisory Committee on Blood and Blood Products. Emergency framework for rationing of blood for massively bleeding patients during a red phase of a blood shortage–synopsis for triage team
. Winnipeg, MB; 2012 Oct 11. http://www.nacblood.ca/resources/shortages-plan/synopsis-triage-team.pdf
43. Smith LB, et al. How do I allocate blood products at the end of life? An ethical analysis with suggested guidelines Transfusion 2013 53 4 696 700
44. 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 6 409 17
45. McIntyre L, et al. Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients? J Trauma 2004 57 3 563 8
46. Dutton RP, et al. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality J Trauma 2002 52 6 1141 6
47. Dutton RP, et al. Trauma mortality in mature trauma systems: are we doing better? An analysis of trauma mortality patterns, 1997-2008 J Trauma 2010 69 3 620 6
48. Handel J, Lang E Transfusion strategy for acute upper gastrointestinal bleeding CJEM 2015 17 5 582 5
49. Michetti CP, et al. Reducing transfusions in critically injured patients using a restricted-criteria order set J Trauma Acute Care Surg 2016 81 5 889 96
50. ARISE Investigators, et al. Goal-directed resuscitation for patients with early septic shock N Engl J Med 2014 371 16 1496 506