Blood Product Selection and Administration

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Blood Product Selection and Administration
Author(s)
Virginia M. Stewart, MD, RDMS
Alicia Devine, MD, JD

Overview

Emergency physicians (EPs) frequently encounter patients requiring blood-product transfusions. Anemia from acute bleeding, emergent reversal of warfarin therapy, and correction of thrombocytopenia are just a few indications for transfusion in the ED. Rapid physician assessment and the timely administration of blood products, including packed red blood cells (PRBCs), platelets, fresh frozen plasma (FFP), cryoprecipitate, and other factors are crucial in resuscitation, and are life-saving in some instances. This article describes the different types of blood products, transfusion indications, complications, and medical decision-making involved.

In 2011, nearly 14 million units of whole blood and RBCs were transfused in US hospitals according to the 2011 National Blood Collection and Utilization Survey Report. In the United States, United Kingdom, Western Europe, and Canada, approximately 40% of critically ill patients received a mean of 5 U of PRBC per hospitalization.1,2

In the ED, hemodynamic instability due to acute hemorrhage is the most common indication for transfusion of PRBCs. Common emergent sources include gastrointestinal (GI) bleeding, dysfunctional uterine bleeding, and bleeding secondary to trauma. For every unit of PRBCs transfused, the typical result in the average adult is an increase in hemoglobin (Hgb) by 1 g/dL and hematocrit by 3%. In the pediatric population, a 3 mL/kg intravenous (IV) dose achieves equivalent results.3

Blood Components and Type Compatibility

After donated blood is collected, blood banks divide the blood into type and components, including red cell concentrate, FFP, cryoprecipitates, and platelets.

Packed Red Blood Cells

After RBCs are separated from whole blood, they can be further processed through leukoreduction, which removes most white blood cells at the expense of a 10% to 15% loss of RBCs. Leukoreduced RBCs (LRBCs) are used in patients with a history of two or more febrile nonhemolytic transfusion reactions (FNHTR). In addition to preventing FNHTR, LRBCs may also be effective in preventing cytomegalovirus (CMV) transmission or human leukocyte antigen (HLA) alloimmunization.4

Cytomegalovirus negative PRBCs and blood components are indicated for the following patients: premature and all infants younger than age 4 weeks; intrauterine transfusions; bone marrow or organ transplant recipients (including transplant candidates); immunocompromised and asplenic patients; and pregnant women.

Irradiated PRBCs and blood products are exposed to 2,500 rad of gamma radiation to destroy lymphoproliferative processes. This irradiation prevents transfusion-associated graft-versus-host disease (TA-GVHD) in susceptible patients. Absolute indications for irradiated blood products include bone marrow transplant recipients and donors, stem-cell donors, T-cell immunodeficiency, intrauterine transfusion, and HLA-matched platelet transfusions. Relative indications include patients with leukemia, Hodgkin disease, non-Hodgkin lymphoma, neonatal exchange transfusion, premature infants, neuroblastoma, and glioblastoma.3

Divided RBC units or “pedi-packs” are derived from dividing single units of PRBCs into 4 units. Pedi-packs are type O irradiated, leukoreduced, and Hgb S negative PRBCs; however, they are not necessarily CMV negative. Pedi-packs minimize blood wasting and donor exposure when a small volume transfusion is indicated.5

Type O

Often, cross-matched blood is not immediately available. If PRBCs are needed within the first 15 minutes of resuscitation and the patient’s condition cannot be stabilized with 2 L of crystalloid fluids, type O blood is warranted. In general, women of childbearing age should be transfused with type O Rh-negative blood.6

Of 4,241 trauma patients who received uncrossmatched PRBCs (URBCs) or type O transfusions in a retrospective study at a level 1 trauma center, those receiving URBCs had a 39.6% mortality compared to 11.9% of those with crossmatched PRBCs (P<.001). In general, the use of URBCs is an independent predictor of mortality after adjusting for gender, mechanism, age, hypotension, intubation, initial Hgb, abbreviated injury scale, Glasgow coma scale, injury severity score, and the amount of blood products received. Crossmatched blood should be used whenever available, and a request for uncrossmatched blood products should trigger the blood bank to release crossmatched blood in anticipation of massive transfusion.7

Platelets

Platelets are separated and concentrated through serial centrifugation, then re-suspended in residual plasma. A therapeutic adult dose is comprised of four to six platelet concentrates of the same blood type. This raises platelet counts by 5,000 mL/U. Even though hemostasis may be maintained at platelet counts of 5,000/mL, it is acceptable to transfuse for platelet counts below 10,000/mL. Patients who are bleeding due to platelet dysfunction, and/or thrombocytopenia require platelets. Platelet transfusion is generally ineffective in the case of immune-mediated platelet consumption such as thrombotic thrombocytopenic purpura (TTP).8

ABO Compatible Platelets

Infants and small children require ABO compatible or volume-reduced platelets.9 Type ABO compatibility is less clinically significant in adults; however, Rh sensitization may occur. Conditions refractory to platelet therapy include fever, sepsis disseminated intravascular coagulation (DIC), splenomegaly, idiopathic thrombocytopenic purpura, and platelet alloimmunization. Patients frequently transfused with platelets or those with platelet alloimmunization require leukoreduced and HLA-matched products to minimize HLA antibody-induced immune destruction.10

 

 

Fresh Frozen Plasma

Plasma is removed from whole blood and frozen below 55˚F to make FFP. It contains all of the coagulation factors but is not a concentrate. Fresh frozen plasma contains both stable and labile components of the fibrinolytic, coagulation, and complement systems, as well as proteins that maintain oncotic pressure. Unlike PRBC, where type O is the universal donor, in FFP, AB type is the universal donor for transfusion. In the ED, FFP is used for the reversal of coagulopathy in bleeding patients and for replacement of coagulation factors when specific factors are unavailable. It is also given to patients requiring large volumes of blood components (ie, massive blood transfusion protocol).10

A typical FFP unit is approximately 250 mL and is administered within 6 hours of thawing. Every 1 mL/kg of body weight of FFP raises clotting factors by 1%. For warfarin reversal, 5 to 8 mL/kg of FFP should be administered IV. One milliliter of FFP has 1 U of activity of all coagulation factors; 15 mL/kg of FFP achieves approximately 30% of plasma factor concentration.10,11

Patients with active bleeding and documented liver disease, congenital factor deficiency, or mass transfusion recipients are candidates for FFP in the ED. Patients with TTP should also receive FFP with plasma exchange. When FFP is administered for emergent reversal in life-threatening bleeding or intracranial hemorrhage, it is given in conjunction with IV vitamin K and either Factor VIIa or prothrombin.12

Cryoprecipitate

Cryoprecipitate contains factor VIII, von Willebrand factor (vWF), and fibrinogen with some amounts of factor XIII and fibronectin. Actively bleeding patients with hypofibrinogenemia (<100 mg/dL fibrin) are candidates for cryoprecipitate. Cryoprecipitate is used in the therapeutic management of hemophilia A (factor VIII deficiency) when factor VIII concentrates are not available. Cryoprecipitate is given as type ABO compatible when possible and, like FFP, type AB is the universal donor. Each unit of cryoprecipitate raises fibrinogen 75 mg/dL, with a typical dose being 10 U or 1 U per 5 kg of patient body weight.13,14

Factor VIII, Von Willebrand Factor, and Factor IX

Patients with hemophilia typically present to the ED with bleeding episodes ranging from benign abrasion to life-threatening epidural hematomas. Factor VIII concentrates are purified from plasma to treat bleeding patients with hemophilia A or von Willebrand disease (VWD). For emergent use, the amount of factor VIII should be calculated as follows: estimated dose = weight (kg) x 0.5 x desired factor (%) increase. The targeted factor VIII increase is typically 80% to 100% for severe bleeding in patients with hemophilia A.

Another component of factor VIII is vWF activity (factor VIII/vWF). Von Willebrand disease is characterized by the lack of factor VIII/vWF, resulting in normal platelet counts and morphologies, but with impaired adhesion ability. Humate-P and Alphanate SD/HT, are factor VIII replacement therapies with significant amounts of vWF, and are approved for use in patients with hemophilia A and vWD. The initial dose of Humate-P for severe bleeding episodes is 40 to 60 U/kg IV. An administered dose of 50 IU/kg of Alphanate is expected to increase circulating FVIII levels to 100% of normal.

Factor IX (FIX) concentrates are used to treat patients with hemophilia B, a condition in which patients lack factor IX, a vitamin K-dependent glycoprotein. The FIX concentrates may also benefit patients with factor X or prothrombin deficiency. In the United States, since 1992, commercially available FIX is produced from genetically engineered recombinant factor replacement (rFIX). Second-generation rFIX and monoclonal antibody solvents do not contain human plasma and are free of viral contaminants, including parvovirus B19.15

Etiology and Treatment

Gastrointestinal Bleeding

Sources of GI bleeding vary from hemorrhoids to Mallory-Weiss tears. The heterogeneous population of patients with GI bleeds complicates the identification of high-risk patients needing transfusion. Bleeding is traditionally characterized as either upper GI bleeding (UGIB) or lower GI bleeding (LGIB)—the former requiring endoscopy, the latter colonoscopy or other expensive strategies to differentiate one form from the other.

In patients with LGIB, the differential diagnosis is broad, ranging from hemorrhoidal bleeding, cancer, or life-threatening diverticular hemorrhage. Prompt volume replacement with isotonic crystalloid IV fluids must be initiated. In nonvariceal UGIB, blood transfusions should be initiated for Hgb levels <70g/L.16

Clinical prediction rules for acute GI bleeding can help identify those patients who require transfusions. One study collected data on seven established independent predictors of severe LGIB, including heart rate, systolic blood pressure (SBP), syncope, nontender abdomen, rectal bleeding in the first 4 hours of evaluation, aspirin use, and more than two comorbid conditions. A nontender abdomen was the best predictor of severe bleeding, likely due to the fact that vascular disorders, such as diverticulitis, result in brisk bleeding without tenderness; whereas inflammatory processes, such as ischemic colitis, are associated with less severe bleeding and abdominal tenderness. Patients with one or more of the seven risk factors were stratified into low (0-7 risk factors), moderate (1-3 risk factors), and high-risk groups (>3 risk factors). Low-risk patients had a ≤ 9% risk of a severe LGIB, moderate-risk patients had a 43% risk, and high-risk patients had >79% likelihood of bleeding. The high-risk patients were more likely to require early transfusion of PRBCs. Tachycardia, hypotension, syncope, nontender abdomen, and rectal bleeding were identified as the most significant predictors of patients requiring 4 or more units of PRBC in the first 24 hours. Such clinical prediction rules may aid in the initial triage of patients with acute LGIB and identify those most likely to require transfusion in the ED.17

 

 

Similar to LGIB transfusion prediction rules, the BLEED (ongoing bleeding, low systolic blood pressure, elevated prothrombin time [PT], erratic mental status, unstable comorbid disease) classification identified patients with UGIB most likely to require transfusion. High-risk patients had one or more of the following: ongoing bleeding, SBP <100 mm Hg, PT more than 1.2 times the control value, altered mental status, the presence of an unstable comorbid disease, or a disease process requiring management in the intensive care unit.18

Trauma

Within the first 48 hours of presentation, blood loss accounts for more than 50% of all trauma deaths.19,20 Posttraumatic bleeding is attributed to several factors, including vascular injury and coagulopathy. Hemodilution from large amounts of crystalloid infusion, hypothermia, and acidosis in early resuscitation adversely affect coagulation, platelet function, protein C consumption, and increases levels of tissue plasminogen activator inhibitor.21 A recent study comparing coagulation tests at the trauma scene and for 1 hour after injury, demonstrated significant activation and consumption of Factors V and XIII, fibrinogen, and proteins C and S.22 Patients with acute coagulopathy of trauma-shock (ACTS) were 4 times more likely to die than those without ACTS.22

In patients with evidence of hemorrhagic shock, hemodynamic instability, and inadequate oxygen (O2) delivery, a restrictive approach to transfusion is favored to maintain a goal hemoglobin of 7 to 9 g/dL. Generally, transfusion is considered when Hgb drops to <7 g/dL, especially in mechanically ventilated and other critically ill patients. Red blood cell transfusion should not be considered the singular or absolute method to improve tissue O2 consumption.23

Obstetric Hemorrhage

Postpartum hemorrhage (PPH) is a catastrophic maternal complication of delivery and a leading cause of maternal morbidity and mortality. Delayed hemorrhage may be seen in the ED days to weeks postpartum. Initial measures to control bleeding include uterine massage, uterotonic medications (ie, oxytocin), and blood-product components. Coagulopathy may be rapidly identified and FFP considered if a clot does not form within 7 minutes in a collection tube containing no anticoagulant (ie, red-top tube).12 During an ED delivery, uterine atony should be anticipated if the uterus is enlarged or the fundus is “doughy.” Atony is the most common cause of PPH within 24 hours and is managed with oxytocin 20 to 30 U/L at 200 mL/h. Alternatively, methylergonovine maleate 0.2 mg may be administered intramuscularly.24

Transfusion Complications

Several immediate complications may arise from transfusion, including intravascular hemolytic transfusion reactions, fever, urticaria, and transfusion-related lung injury (TRALI). Delayed complications include extravascular hemolytic reactions, and TA-GVHD. Other complications include acute bacteremia from contamination, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and transfusion-associated circulatory overload (TACO).

Intravascular Hemolytic Reactions

Intravascular hemolytic reactions resulting from ABO incompatibility are the most severe transfusion complication. Immediate onset symptoms include fever, chills, headache, nausea, vomiting, chest discomfort, and severe back pain. Treatment involves immediate cessation of the transfusion, replacement of all tubing components, and aggressive IV crystalloid fluid therapy with diuretics to maintain a urine output of 1 to 2 mL/kg/h. All remaining blood, along with the patient’s blood and urine samples, should be sent to the laboratory to detect free Hgb. A positive Coombs test on the posttransfusion blood confirms the diagnosis.

The most common reaction is a 1°C temperature elevation with no other cause. Treatment for fever and urticaria consists of antihistamines and antipyretics. However, febrile patients receiving blood for the first time should be managed as an intravascular hemolytic transfusion reaction until proved otherwise by a negative Coombs test. Mild reactions may be due to an allergic response to donor plasma proteins, but in patients with genetic immunoglobulin A (IgA) deficiency can represent an afebrile life-threatening reaction characterized by hypotension and respiratory symptoms. An IgA deficiency should be considered in patients of European descent as a cause of transfusion-related anaphylactic reactions.25

Transfusion-related Acute Lung Injury

The most common cause of mortality from transfusions is due to transfusion-related acute lung injury (TRALI), which presents within the first 6 hours of transfusion. Signs and symptoms of TRALI include noncardiogenic pulmonary edema, dyspnea, hypoxemia, fever, and hypotension. A portable chest X-ray may reveal bilateral infiltrates, and a complete blood count may demonstrate transient leukopenia. While the underlying mechanism is likely multifactorial, TRALI may be precipitated by a “leaky” pulmonary endothelium as a direct or indirect result of antibodies against the recipient. One strategy to reduce the incidence of TRALI is to use male donors for plasma to reduce the incidence of allotypic leukocyte antibodies that can occur in women who have had prior pregnancies. Management of TRALI includes immediately stopping the transfusion, notifying the blood bank, and providing respiratory support. Blood products may be transfused from a different donor. Unlike TACO or cardiogenic pulmonary edema, TRALI demonstrates no evidence of circulatory overload, and it does not respond to diuretic therapy.26 Circulatory overload may be avoided by infusing a single unit of PRBCs over 4 hours.

 

 

Extravascular Hemolytic Reactions

Delayed extravascular hemolytic reactions are most likely due to previous sensitization to red cell antigens from prior transfusion, pregnancy, or transplant. Extravascular hemolysis can occur days to weeks after repeat exposure. Patients present with fever, anemia, and jaundice without hemoglobinemia or hemoglobinuria. Symptoms are usually benign, though oliguria and DIC have been reported.27,28

Transfusion-associated graft-versus-host disease is a delayed extravascular hemolytic reaction that occurs in immunosuppressed recipients of transfused blood. Most deaths are due to coagulopathy or infection. Transfused lymphocytes proliferate and attack the blood recipient. Symptoms (eg, fever, rash, diarrhea, elevated liver transaminases, pancytopenia) begin 3 to 30 days posttransfusion, and a bone marrow transplant is indicated. Irradiated and leukoreduced blood components prevent TA-GVHD.29,30

Bacteremia and Viral Infection

Among significant bacterial contaminants from donor blood, Yersinia enterocolitica is the most common and has a mortality rate of greater than 50%.31 Typical symptoms include rigors, vomiting, abdominal cramps, fever, shock, renal failure, or DIC during transfusion. Immediate cessation of blood products and broad spectrum antibiotics are warranted. Risks among viral contaminants include human immunodeficiency disease (HIV), CMV, and hepatitis. Hepatitis B infection occurs in one in 1 million transfusion recipients, while the risk of hepatitis C is one in 1.2 million and HIV infection one in 1.5 million.32,33

Electrolyte Derangement

Electrolyte derangements after multiple-unit transfusions include hypocalcemia, hyperkalemia, and acid-base disorders. Massive blood transfusions with blood anticoagulated with sodium citrate and citric acid may contribute to metabolic alkalosis and hypocalcemia. Potassium may move into cells in exchange for hydrogen ions moving out of cells to minimize extracellular alkalosis, contributing to hypokalemia.34-36 To avoid hypocalcemia and alkalosis, the maximum citrate infusion rate should be 0.02 mmol/kg/minute, with the citrate concentration in whole blood measured as 15 mmol/L. If liver function is impaired in the setting of hypocalcemia-related blood transfusion, calcium chloride is preferred over calcium gluconate because it decreases citrate metabolism resulting in a slower release of ionized calcium.37 Calcium replacement should be considered in patients with liver dysfunction or patients with normal liver function who have received greater than 10 U pRBCs per hour. Calcium chloride (10%) is preferred over calcium gluconate to correct ionized hypocalcemia with 2 to 5 mL given for every 500mL of blood.37 Hyperkalemia risks are minimized by avoiding prolonged blood storage or irradiation.38

Conclusion

Timely administration of blood products is crucial in resuscitation and can be life-saving in a variety of bleeding disorders. Emergent reversal of warfarin therapy, correction of thrombocytopenia, bleeding due to hemophilia, GI bleeding, trauma, and obstetric hemorrhage are among the most common disorders managed in the ED. To select the most appropriate treatment, one must know the merits of the various blood products including PRBCs, platelets, FFP, and cryoprecipitate. The clinician must also be prepared to manage the immediate complications that may arise from transfusion including intravascular hemolytic reactions, fever, urticaria, and TRALI, as well as the delayed complications of extravascular hemolytic reactions, TA-GVHD, acute bacteremia, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and TACO.

Dr Stewart is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, Virginia, and Riverside Medical Group, Newport News, Virginia. Dr Devine is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, and Emergency Physicians of Tidewater, Norfolk, Virginia. The authors report no conflicts of interest.

References

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  3. Carson JL, Grossman BJ, Kleinman S, et al; Clinical Transfusion Medicine Committee of the AABB. Red blood cell transfusion: a clinical practice guideline from the AAAB. Ann Intern Med. 2012;157(1):49-58.
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  5. van Straaten HL, de Wildt-Eggen J, Huisveld IA. Evaluation of a strategy to limit blood donor exposure in high risk premature newborns based on clinical estimation of transfusion need. J Perniat Med. 2000;28(2):122-128.
  6. Anstee DJ. Red cell genotyping and the future of pretransfusion testing. Blood. 2009;114(2):248-256.
  7. Inaba K, Teixeira PG, Shulman I. The impact of uncross-matched blood transfusion on the need for massive transfusion and mortality: analysis of 5,166 uncross-matched units. J Trauma. 2008;65(6):1222-1226.
  8. Slichter SJ. Platelet transfusion therapy.  Hematol Oncol Clin North Am. 2007;21(4):697-729.
  9. Uppal P, Lodha R, Kabra SK. Transfusion of blood and components in critically ill children. Indian J Pediatr. 2010;77(12):1424-1428.
  10. Shah A, Stanworth SJ, McKechnie. Evidence and triggers for the transfusion of blood and blood products. Anesthesia. 2015;70(Suppl 1):10-19.
  11. Emery, M. Blood and Blood Components. In: Marx JA, Hockberger RS, Walls RM ed. Rosen’s emergency medicine: concepts and clinical practice. 7th ed. Philadelphia, PA: Mosby/Elsevier; 2009:42-46.
  12. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
  13. Santen S A Transfusion Therapy. In: Tintinalli, J. E., Kelen, G. D., & Stapczynski, J. S. ed. Emergency medicine: a comprehensive study guide. 6th ed. New York, NY: McGraw-Hill Medical; 20041349-1351.
  14. Osterman JL, Arora S. Blood product transfusions and reactions. Emerg Med Clin North Am. 2014;32(3): 727-738.
  15. Azzi A, De Santis R, Morfini M, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood. 2001;98(8):2571-2573.
  16. Barkun AN, Bardou M, Kuipers EJ, et al; International Consensus Upper Gastrointestinal Bleeding Conference Group International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101-113.
  17. Strate L, Saltzman J, and Ookubo R. Validation of a clinical prediction rule for severe acute lower intestinal bleeding. Am J Gastroenterol. 2005;100(8):1821-1827.
  18. Kollef MH, O’Brien JD, Zuckerman GR, Shannon W. BLEED: a classification tool to predict outcomes in patients with acute upper and lower gastrointestinal hemorrhage. Crit Care Med. 1997;25(7):1125-1132.
  19. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185-193.
  20. Simmons JW, Pittet JF, Pierce B. Trauma-induced coagulopathy. Curr Anesthisiol Rep. 2014;4(3):189-199.
  21. Zehtabchi S, Nishijima DK. Impact of transfusion of fresh-frozen plasma and packed red blood cells in a 1:1 ratio on survival of emergency department patients with severe trauma. Acad Emerg Med. 2009;16(5):371-378.
  22. Theusinger OM, Baulig W, Seifert B, Müller SM, Mariotti S, Spahn DR.. Changes in coagulation in standard laboratory tests and ROTEM in trauma patients between on-scene and arrival in the emergency department. Anesth Analg. 2014. [Epub ahead of print]
  23. Bouillon B, Brohi K, Hess JR, Holcomb JB, Parr MJ, Hoyt DB. Educational initiative on critical bleeding in trauma: Chicago, July 11-13, 2008. J Trauma. 2010;68(1):225-230.
  24. Phillips LE, McLintock C, Pollock W, et al; Australian and New Zealand Haemostasis Registry. Recombinant activated Factor VII in obstetric hemorrhage: experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg. 2009;109(6):1908-1915.
  25. Hirayama F. Current understanding of allergic transfusion reactions: incidence, pathogenesis, laboratory tests, prevention and treatment. Br J Haematol. 2013;160(4);434-444.
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  27. Welling KL, Taaning E, Lund BV, Rosenkvist J, Heslet L. Post-transfusion purpura (PTP) and disseminated intravascular coagulation (DIC). Eur J Haematol. 2003;71(1):68-71
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  29. Przepiorka D, LeParc GF, Stovall MA, Werch J, Lichtiger B. Use of irradiated blood components: practice parameter. Am J Clin Pathol. 1996;106(1):6-11.
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  33. Zou S, Stramer SL, Dodd RY. Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogenic donations. Transfus Med Rev. 2012;26(2):119-128.
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Alicia Devine, MD, JD
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Alicia Devine, MD, JD
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Overview

Emergency physicians (EPs) frequently encounter patients requiring blood-product transfusions. Anemia from acute bleeding, emergent reversal of warfarin therapy, and correction of thrombocytopenia are just a few indications for transfusion in the ED. Rapid physician assessment and the timely administration of blood products, including packed red blood cells (PRBCs), platelets, fresh frozen plasma (FFP), cryoprecipitate, and other factors are crucial in resuscitation, and are life-saving in some instances. This article describes the different types of blood products, transfusion indications, complications, and medical decision-making involved.

In 2011, nearly 14 million units of whole blood and RBCs were transfused in US hospitals according to the 2011 National Blood Collection and Utilization Survey Report. In the United States, United Kingdom, Western Europe, and Canada, approximately 40% of critically ill patients received a mean of 5 U of PRBC per hospitalization.1,2

In the ED, hemodynamic instability due to acute hemorrhage is the most common indication for transfusion of PRBCs. Common emergent sources include gastrointestinal (GI) bleeding, dysfunctional uterine bleeding, and bleeding secondary to trauma. For every unit of PRBCs transfused, the typical result in the average adult is an increase in hemoglobin (Hgb) by 1 g/dL and hematocrit by 3%. In the pediatric population, a 3 mL/kg intravenous (IV) dose achieves equivalent results.3

Blood Components and Type Compatibility

After donated blood is collected, blood banks divide the blood into type and components, including red cell concentrate, FFP, cryoprecipitates, and platelets.

Packed Red Blood Cells

After RBCs are separated from whole blood, they can be further processed through leukoreduction, which removes most white blood cells at the expense of a 10% to 15% loss of RBCs. Leukoreduced RBCs (LRBCs) are used in patients with a history of two or more febrile nonhemolytic transfusion reactions (FNHTR). In addition to preventing FNHTR, LRBCs may also be effective in preventing cytomegalovirus (CMV) transmission or human leukocyte antigen (HLA) alloimmunization.4

Cytomegalovirus negative PRBCs and blood components are indicated for the following patients: premature and all infants younger than age 4 weeks; intrauterine transfusions; bone marrow or organ transplant recipients (including transplant candidates); immunocompromised and asplenic patients; and pregnant women.

Irradiated PRBCs and blood products are exposed to 2,500 rad of gamma radiation to destroy lymphoproliferative processes. This irradiation prevents transfusion-associated graft-versus-host disease (TA-GVHD) in susceptible patients. Absolute indications for irradiated blood products include bone marrow transplant recipients and donors, stem-cell donors, T-cell immunodeficiency, intrauterine transfusion, and HLA-matched platelet transfusions. Relative indications include patients with leukemia, Hodgkin disease, non-Hodgkin lymphoma, neonatal exchange transfusion, premature infants, neuroblastoma, and glioblastoma.3

Divided RBC units or “pedi-packs” are derived from dividing single units of PRBCs into 4 units. Pedi-packs are type O irradiated, leukoreduced, and Hgb S negative PRBCs; however, they are not necessarily CMV negative. Pedi-packs minimize blood wasting and donor exposure when a small volume transfusion is indicated.5

Type O

Often, cross-matched blood is not immediately available. If PRBCs are needed within the first 15 minutes of resuscitation and the patient’s condition cannot be stabilized with 2 L of crystalloid fluids, type O blood is warranted. In general, women of childbearing age should be transfused with type O Rh-negative blood.6

Of 4,241 trauma patients who received uncrossmatched PRBCs (URBCs) or type O transfusions in a retrospective study at a level 1 trauma center, those receiving URBCs had a 39.6% mortality compared to 11.9% of those with crossmatched PRBCs (P<.001). In general, the use of URBCs is an independent predictor of mortality after adjusting for gender, mechanism, age, hypotension, intubation, initial Hgb, abbreviated injury scale, Glasgow coma scale, injury severity score, and the amount of blood products received. Crossmatched blood should be used whenever available, and a request for uncrossmatched blood products should trigger the blood bank to release crossmatched blood in anticipation of massive transfusion.7

Platelets

Platelets are separated and concentrated through serial centrifugation, then re-suspended in residual plasma. A therapeutic adult dose is comprised of four to six platelet concentrates of the same blood type. This raises platelet counts by 5,000 mL/U. Even though hemostasis may be maintained at platelet counts of 5,000/mL, it is acceptable to transfuse for platelet counts below 10,000/mL. Patients who are bleeding due to platelet dysfunction, and/or thrombocytopenia require platelets. Platelet transfusion is generally ineffective in the case of immune-mediated platelet consumption such as thrombotic thrombocytopenic purpura (TTP).8

ABO Compatible Platelets

Infants and small children require ABO compatible or volume-reduced platelets.9 Type ABO compatibility is less clinically significant in adults; however, Rh sensitization may occur. Conditions refractory to platelet therapy include fever, sepsis disseminated intravascular coagulation (DIC), splenomegaly, idiopathic thrombocytopenic purpura, and platelet alloimmunization. Patients frequently transfused with platelets or those with platelet alloimmunization require leukoreduced and HLA-matched products to minimize HLA antibody-induced immune destruction.10

 

 

Fresh Frozen Plasma

Plasma is removed from whole blood and frozen below 55˚F to make FFP. It contains all of the coagulation factors but is not a concentrate. Fresh frozen plasma contains both stable and labile components of the fibrinolytic, coagulation, and complement systems, as well as proteins that maintain oncotic pressure. Unlike PRBC, where type O is the universal donor, in FFP, AB type is the universal donor for transfusion. In the ED, FFP is used for the reversal of coagulopathy in bleeding patients and for replacement of coagulation factors when specific factors are unavailable. It is also given to patients requiring large volumes of blood components (ie, massive blood transfusion protocol).10

A typical FFP unit is approximately 250 mL and is administered within 6 hours of thawing. Every 1 mL/kg of body weight of FFP raises clotting factors by 1%. For warfarin reversal, 5 to 8 mL/kg of FFP should be administered IV. One milliliter of FFP has 1 U of activity of all coagulation factors; 15 mL/kg of FFP achieves approximately 30% of plasma factor concentration.10,11

Patients with active bleeding and documented liver disease, congenital factor deficiency, or mass transfusion recipients are candidates for FFP in the ED. Patients with TTP should also receive FFP with plasma exchange. When FFP is administered for emergent reversal in life-threatening bleeding or intracranial hemorrhage, it is given in conjunction with IV vitamin K and either Factor VIIa or prothrombin.12

Cryoprecipitate

Cryoprecipitate contains factor VIII, von Willebrand factor (vWF), and fibrinogen with some amounts of factor XIII and fibronectin. Actively bleeding patients with hypofibrinogenemia (<100 mg/dL fibrin) are candidates for cryoprecipitate. Cryoprecipitate is used in the therapeutic management of hemophilia A (factor VIII deficiency) when factor VIII concentrates are not available. Cryoprecipitate is given as type ABO compatible when possible and, like FFP, type AB is the universal donor. Each unit of cryoprecipitate raises fibrinogen 75 mg/dL, with a typical dose being 10 U or 1 U per 5 kg of patient body weight.13,14

Factor VIII, Von Willebrand Factor, and Factor IX

Patients with hemophilia typically present to the ED with bleeding episodes ranging from benign abrasion to life-threatening epidural hematomas. Factor VIII concentrates are purified from plasma to treat bleeding patients with hemophilia A or von Willebrand disease (VWD). For emergent use, the amount of factor VIII should be calculated as follows: estimated dose = weight (kg) x 0.5 x desired factor (%) increase. The targeted factor VIII increase is typically 80% to 100% for severe bleeding in patients with hemophilia A.

Another component of factor VIII is vWF activity (factor VIII/vWF). Von Willebrand disease is characterized by the lack of factor VIII/vWF, resulting in normal platelet counts and morphologies, but with impaired adhesion ability. Humate-P and Alphanate SD/HT, are factor VIII replacement therapies with significant amounts of vWF, and are approved for use in patients with hemophilia A and vWD. The initial dose of Humate-P for severe bleeding episodes is 40 to 60 U/kg IV. An administered dose of 50 IU/kg of Alphanate is expected to increase circulating FVIII levels to 100% of normal.

Factor IX (FIX) concentrates are used to treat patients with hemophilia B, a condition in which patients lack factor IX, a vitamin K-dependent glycoprotein. The FIX concentrates may also benefit patients with factor X or prothrombin deficiency. In the United States, since 1992, commercially available FIX is produced from genetically engineered recombinant factor replacement (rFIX). Second-generation rFIX and monoclonal antibody solvents do not contain human plasma and are free of viral contaminants, including parvovirus B19.15

Etiology and Treatment

Gastrointestinal Bleeding

Sources of GI bleeding vary from hemorrhoids to Mallory-Weiss tears. The heterogeneous population of patients with GI bleeds complicates the identification of high-risk patients needing transfusion. Bleeding is traditionally characterized as either upper GI bleeding (UGIB) or lower GI bleeding (LGIB)—the former requiring endoscopy, the latter colonoscopy or other expensive strategies to differentiate one form from the other.

In patients with LGIB, the differential diagnosis is broad, ranging from hemorrhoidal bleeding, cancer, or life-threatening diverticular hemorrhage. Prompt volume replacement with isotonic crystalloid IV fluids must be initiated. In nonvariceal UGIB, blood transfusions should be initiated for Hgb levels <70g/L.16

Clinical prediction rules for acute GI bleeding can help identify those patients who require transfusions. One study collected data on seven established independent predictors of severe LGIB, including heart rate, systolic blood pressure (SBP), syncope, nontender abdomen, rectal bleeding in the first 4 hours of evaluation, aspirin use, and more than two comorbid conditions. A nontender abdomen was the best predictor of severe bleeding, likely due to the fact that vascular disorders, such as diverticulitis, result in brisk bleeding without tenderness; whereas inflammatory processes, such as ischemic colitis, are associated with less severe bleeding and abdominal tenderness. Patients with one or more of the seven risk factors were stratified into low (0-7 risk factors), moderate (1-3 risk factors), and high-risk groups (>3 risk factors). Low-risk patients had a ≤ 9% risk of a severe LGIB, moderate-risk patients had a 43% risk, and high-risk patients had >79% likelihood of bleeding. The high-risk patients were more likely to require early transfusion of PRBCs. Tachycardia, hypotension, syncope, nontender abdomen, and rectal bleeding were identified as the most significant predictors of patients requiring 4 or more units of PRBC in the first 24 hours. Such clinical prediction rules may aid in the initial triage of patients with acute LGIB and identify those most likely to require transfusion in the ED.17

 

 

Similar to LGIB transfusion prediction rules, the BLEED (ongoing bleeding, low systolic blood pressure, elevated prothrombin time [PT], erratic mental status, unstable comorbid disease) classification identified patients with UGIB most likely to require transfusion. High-risk patients had one or more of the following: ongoing bleeding, SBP <100 mm Hg, PT more than 1.2 times the control value, altered mental status, the presence of an unstable comorbid disease, or a disease process requiring management in the intensive care unit.18

Trauma

Within the first 48 hours of presentation, blood loss accounts for more than 50% of all trauma deaths.19,20 Posttraumatic bleeding is attributed to several factors, including vascular injury and coagulopathy. Hemodilution from large amounts of crystalloid infusion, hypothermia, and acidosis in early resuscitation adversely affect coagulation, platelet function, protein C consumption, and increases levels of tissue plasminogen activator inhibitor.21 A recent study comparing coagulation tests at the trauma scene and for 1 hour after injury, demonstrated significant activation and consumption of Factors V and XIII, fibrinogen, and proteins C and S.22 Patients with acute coagulopathy of trauma-shock (ACTS) were 4 times more likely to die than those without ACTS.22

In patients with evidence of hemorrhagic shock, hemodynamic instability, and inadequate oxygen (O2) delivery, a restrictive approach to transfusion is favored to maintain a goal hemoglobin of 7 to 9 g/dL. Generally, transfusion is considered when Hgb drops to <7 g/dL, especially in mechanically ventilated and other critically ill patients. Red blood cell transfusion should not be considered the singular or absolute method to improve tissue O2 consumption.23

Obstetric Hemorrhage

Postpartum hemorrhage (PPH) is a catastrophic maternal complication of delivery and a leading cause of maternal morbidity and mortality. Delayed hemorrhage may be seen in the ED days to weeks postpartum. Initial measures to control bleeding include uterine massage, uterotonic medications (ie, oxytocin), and blood-product components. Coagulopathy may be rapidly identified and FFP considered if a clot does not form within 7 minutes in a collection tube containing no anticoagulant (ie, red-top tube).12 During an ED delivery, uterine atony should be anticipated if the uterus is enlarged or the fundus is “doughy.” Atony is the most common cause of PPH within 24 hours and is managed with oxytocin 20 to 30 U/L at 200 mL/h. Alternatively, methylergonovine maleate 0.2 mg may be administered intramuscularly.24

Transfusion Complications

Several immediate complications may arise from transfusion, including intravascular hemolytic transfusion reactions, fever, urticaria, and transfusion-related lung injury (TRALI). Delayed complications include extravascular hemolytic reactions, and TA-GVHD. Other complications include acute bacteremia from contamination, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and transfusion-associated circulatory overload (TACO).

Intravascular Hemolytic Reactions

Intravascular hemolytic reactions resulting from ABO incompatibility are the most severe transfusion complication. Immediate onset symptoms include fever, chills, headache, nausea, vomiting, chest discomfort, and severe back pain. Treatment involves immediate cessation of the transfusion, replacement of all tubing components, and aggressive IV crystalloid fluid therapy with diuretics to maintain a urine output of 1 to 2 mL/kg/h. All remaining blood, along with the patient’s blood and urine samples, should be sent to the laboratory to detect free Hgb. A positive Coombs test on the posttransfusion blood confirms the diagnosis.

The most common reaction is a 1°C temperature elevation with no other cause. Treatment for fever and urticaria consists of antihistamines and antipyretics. However, febrile patients receiving blood for the first time should be managed as an intravascular hemolytic transfusion reaction until proved otherwise by a negative Coombs test. Mild reactions may be due to an allergic response to donor plasma proteins, but in patients with genetic immunoglobulin A (IgA) deficiency can represent an afebrile life-threatening reaction characterized by hypotension and respiratory symptoms. An IgA deficiency should be considered in patients of European descent as a cause of transfusion-related anaphylactic reactions.25

Transfusion-related Acute Lung Injury

The most common cause of mortality from transfusions is due to transfusion-related acute lung injury (TRALI), which presents within the first 6 hours of transfusion. Signs and symptoms of TRALI include noncardiogenic pulmonary edema, dyspnea, hypoxemia, fever, and hypotension. A portable chest X-ray may reveal bilateral infiltrates, and a complete blood count may demonstrate transient leukopenia. While the underlying mechanism is likely multifactorial, TRALI may be precipitated by a “leaky” pulmonary endothelium as a direct or indirect result of antibodies against the recipient. One strategy to reduce the incidence of TRALI is to use male donors for plasma to reduce the incidence of allotypic leukocyte antibodies that can occur in women who have had prior pregnancies. Management of TRALI includes immediately stopping the transfusion, notifying the blood bank, and providing respiratory support. Blood products may be transfused from a different donor. Unlike TACO or cardiogenic pulmonary edema, TRALI demonstrates no evidence of circulatory overload, and it does not respond to diuretic therapy.26 Circulatory overload may be avoided by infusing a single unit of PRBCs over 4 hours.

 

 

Extravascular Hemolytic Reactions

Delayed extravascular hemolytic reactions are most likely due to previous sensitization to red cell antigens from prior transfusion, pregnancy, or transplant. Extravascular hemolysis can occur days to weeks after repeat exposure. Patients present with fever, anemia, and jaundice without hemoglobinemia or hemoglobinuria. Symptoms are usually benign, though oliguria and DIC have been reported.27,28

Transfusion-associated graft-versus-host disease is a delayed extravascular hemolytic reaction that occurs in immunosuppressed recipients of transfused blood. Most deaths are due to coagulopathy or infection. Transfused lymphocytes proliferate and attack the blood recipient. Symptoms (eg, fever, rash, diarrhea, elevated liver transaminases, pancytopenia) begin 3 to 30 days posttransfusion, and a bone marrow transplant is indicated. Irradiated and leukoreduced blood components prevent TA-GVHD.29,30

Bacteremia and Viral Infection

Among significant bacterial contaminants from donor blood, Yersinia enterocolitica is the most common and has a mortality rate of greater than 50%.31 Typical symptoms include rigors, vomiting, abdominal cramps, fever, shock, renal failure, or DIC during transfusion. Immediate cessation of blood products and broad spectrum antibiotics are warranted. Risks among viral contaminants include human immunodeficiency disease (HIV), CMV, and hepatitis. Hepatitis B infection occurs in one in 1 million transfusion recipients, while the risk of hepatitis C is one in 1.2 million and HIV infection one in 1.5 million.32,33

Electrolyte Derangement

Electrolyte derangements after multiple-unit transfusions include hypocalcemia, hyperkalemia, and acid-base disorders. Massive blood transfusions with blood anticoagulated with sodium citrate and citric acid may contribute to metabolic alkalosis and hypocalcemia. Potassium may move into cells in exchange for hydrogen ions moving out of cells to minimize extracellular alkalosis, contributing to hypokalemia.34-36 To avoid hypocalcemia and alkalosis, the maximum citrate infusion rate should be 0.02 mmol/kg/minute, with the citrate concentration in whole blood measured as 15 mmol/L. If liver function is impaired in the setting of hypocalcemia-related blood transfusion, calcium chloride is preferred over calcium gluconate because it decreases citrate metabolism resulting in a slower release of ionized calcium.37 Calcium replacement should be considered in patients with liver dysfunction or patients with normal liver function who have received greater than 10 U pRBCs per hour. Calcium chloride (10%) is preferred over calcium gluconate to correct ionized hypocalcemia with 2 to 5 mL given for every 500mL of blood.37 Hyperkalemia risks are minimized by avoiding prolonged blood storage or irradiation.38

Conclusion

Timely administration of blood products is crucial in resuscitation and can be life-saving in a variety of bleeding disorders. Emergent reversal of warfarin therapy, correction of thrombocytopenia, bleeding due to hemophilia, GI bleeding, trauma, and obstetric hemorrhage are among the most common disorders managed in the ED. To select the most appropriate treatment, one must know the merits of the various blood products including PRBCs, platelets, FFP, and cryoprecipitate. The clinician must also be prepared to manage the immediate complications that may arise from transfusion including intravascular hemolytic reactions, fever, urticaria, and TRALI, as well as the delayed complications of extravascular hemolytic reactions, TA-GVHD, acute bacteremia, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and TACO.

Dr Stewart is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, Virginia, and Riverside Medical Group, Newport News, Virginia. Dr Devine is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, and Emergency Physicians of Tidewater, Norfolk, Virginia. The authors report no conflicts of interest.

Overview

Emergency physicians (EPs) frequently encounter patients requiring blood-product transfusions. Anemia from acute bleeding, emergent reversal of warfarin therapy, and correction of thrombocytopenia are just a few indications for transfusion in the ED. Rapid physician assessment and the timely administration of blood products, including packed red blood cells (PRBCs), platelets, fresh frozen plasma (FFP), cryoprecipitate, and other factors are crucial in resuscitation, and are life-saving in some instances. This article describes the different types of blood products, transfusion indications, complications, and medical decision-making involved.

In 2011, nearly 14 million units of whole blood and RBCs were transfused in US hospitals according to the 2011 National Blood Collection and Utilization Survey Report. In the United States, United Kingdom, Western Europe, and Canada, approximately 40% of critically ill patients received a mean of 5 U of PRBC per hospitalization.1,2

In the ED, hemodynamic instability due to acute hemorrhage is the most common indication for transfusion of PRBCs. Common emergent sources include gastrointestinal (GI) bleeding, dysfunctional uterine bleeding, and bleeding secondary to trauma. For every unit of PRBCs transfused, the typical result in the average adult is an increase in hemoglobin (Hgb) by 1 g/dL and hematocrit by 3%. In the pediatric population, a 3 mL/kg intravenous (IV) dose achieves equivalent results.3

Blood Components and Type Compatibility

After donated blood is collected, blood banks divide the blood into type and components, including red cell concentrate, FFP, cryoprecipitates, and platelets.

Packed Red Blood Cells

After RBCs are separated from whole blood, they can be further processed through leukoreduction, which removes most white blood cells at the expense of a 10% to 15% loss of RBCs. Leukoreduced RBCs (LRBCs) are used in patients with a history of two or more febrile nonhemolytic transfusion reactions (FNHTR). In addition to preventing FNHTR, LRBCs may also be effective in preventing cytomegalovirus (CMV) transmission or human leukocyte antigen (HLA) alloimmunization.4

Cytomegalovirus negative PRBCs and blood components are indicated for the following patients: premature and all infants younger than age 4 weeks; intrauterine transfusions; bone marrow or organ transplant recipients (including transplant candidates); immunocompromised and asplenic patients; and pregnant women.

Irradiated PRBCs and blood products are exposed to 2,500 rad of gamma radiation to destroy lymphoproliferative processes. This irradiation prevents transfusion-associated graft-versus-host disease (TA-GVHD) in susceptible patients. Absolute indications for irradiated blood products include bone marrow transplant recipients and donors, stem-cell donors, T-cell immunodeficiency, intrauterine transfusion, and HLA-matched platelet transfusions. Relative indications include patients with leukemia, Hodgkin disease, non-Hodgkin lymphoma, neonatal exchange transfusion, premature infants, neuroblastoma, and glioblastoma.3

Divided RBC units or “pedi-packs” are derived from dividing single units of PRBCs into 4 units. Pedi-packs are type O irradiated, leukoreduced, and Hgb S negative PRBCs; however, they are not necessarily CMV negative. Pedi-packs minimize blood wasting and donor exposure when a small volume transfusion is indicated.5

Type O

Often, cross-matched blood is not immediately available. If PRBCs are needed within the first 15 minutes of resuscitation and the patient’s condition cannot be stabilized with 2 L of crystalloid fluids, type O blood is warranted. In general, women of childbearing age should be transfused with type O Rh-negative blood.6

Of 4,241 trauma patients who received uncrossmatched PRBCs (URBCs) or type O transfusions in a retrospective study at a level 1 trauma center, those receiving URBCs had a 39.6% mortality compared to 11.9% of those with crossmatched PRBCs (P<.001). In general, the use of URBCs is an independent predictor of mortality after adjusting for gender, mechanism, age, hypotension, intubation, initial Hgb, abbreviated injury scale, Glasgow coma scale, injury severity score, and the amount of blood products received. Crossmatched blood should be used whenever available, and a request for uncrossmatched blood products should trigger the blood bank to release crossmatched blood in anticipation of massive transfusion.7

Platelets

Platelets are separated and concentrated through serial centrifugation, then re-suspended in residual plasma. A therapeutic adult dose is comprised of four to six platelet concentrates of the same blood type. This raises platelet counts by 5,000 mL/U. Even though hemostasis may be maintained at platelet counts of 5,000/mL, it is acceptable to transfuse for platelet counts below 10,000/mL. Patients who are bleeding due to platelet dysfunction, and/or thrombocytopenia require platelets. Platelet transfusion is generally ineffective in the case of immune-mediated platelet consumption such as thrombotic thrombocytopenic purpura (TTP).8

ABO Compatible Platelets

Infants and small children require ABO compatible or volume-reduced platelets.9 Type ABO compatibility is less clinically significant in adults; however, Rh sensitization may occur. Conditions refractory to platelet therapy include fever, sepsis disseminated intravascular coagulation (DIC), splenomegaly, idiopathic thrombocytopenic purpura, and platelet alloimmunization. Patients frequently transfused with platelets or those with platelet alloimmunization require leukoreduced and HLA-matched products to minimize HLA antibody-induced immune destruction.10

 

 

Fresh Frozen Plasma

Plasma is removed from whole blood and frozen below 55˚F to make FFP. It contains all of the coagulation factors but is not a concentrate. Fresh frozen plasma contains both stable and labile components of the fibrinolytic, coagulation, and complement systems, as well as proteins that maintain oncotic pressure. Unlike PRBC, where type O is the universal donor, in FFP, AB type is the universal donor for transfusion. In the ED, FFP is used for the reversal of coagulopathy in bleeding patients and for replacement of coagulation factors when specific factors are unavailable. It is also given to patients requiring large volumes of blood components (ie, massive blood transfusion protocol).10

A typical FFP unit is approximately 250 mL and is administered within 6 hours of thawing. Every 1 mL/kg of body weight of FFP raises clotting factors by 1%. For warfarin reversal, 5 to 8 mL/kg of FFP should be administered IV. One milliliter of FFP has 1 U of activity of all coagulation factors; 15 mL/kg of FFP achieves approximately 30% of plasma factor concentration.10,11

Patients with active bleeding and documented liver disease, congenital factor deficiency, or mass transfusion recipients are candidates for FFP in the ED. Patients with TTP should also receive FFP with plasma exchange. When FFP is administered for emergent reversal in life-threatening bleeding or intracranial hemorrhage, it is given in conjunction with IV vitamin K and either Factor VIIa or prothrombin.12

Cryoprecipitate

Cryoprecipitate contains factor VIII, von Willebrand factor (vWF), and fibrinogen with some amounts of factor XIII and fibronectin. Actively bleeding patients with hypofibrinogenemia (<100 mg/dL fibrin) are candidates for cryoprecipitate. Cryoprecipitate is used in the therapeutic management of hemophilia A (factor VIII deficiency) when factor VIII concentrates are not available. Cryoprecipitate is given as type ABO compatible when possible and, like FFP, type AB is the universal donor. Each unit of cryoprecipitate raises fibrinogen 75 mg/dL, with a typical dose being 10 U or 1 U per 5 kg of patient body weight.13,14

Factor VIII, Von Willebrand Factor, and Factor IX

Patients with hemophilia typically present to the ED with bleeding episodes ranging from benign abrasion to life-threatening epidural hematomas. Factor VIII concentrates are purified from plasma to treat bleeding patients with hemophilia A or von Willebrand disease (VWD). For emergent use, the amount of factor VIII should be calculated as follows: estimated dose = weight (kg) x 0.5 x desired factor (%) increase. The targeted factor VIII increase is typically 80% to 100% for severe bleeding in patients with hemophilia A.

Another component of factor VIII is vWF activity (factor VIII/vWF). Von Willebrand disease is characterized by the lack of factor VIII/vWF, resulting in normal platelet counts and morphologies, but with impaired adhesion ability. Humate-P and Alphanate SD/HT, are factor VIII replacement therapies with significant amounts of vWF, and are approved for use in patients with hemophilia A and vWD. The initial dose of Humate-P for severe bleeding episodes is 40 to 60 U/kg IV. An administered dose of 50 IU/kg of Alphanate is expected to increase circulating FVIII levels to 100% of normal.

Factor IX (FIX) concentrates are used to treat patients with hemophilia B, a condition in which patients lack factor IX, a vitamin K-dependent glycoprotein. The FIX concentrates may also benefit patients with factor X or prothrombin deficiency. In the United States, since 1992, commercially available FIX is produced from genetically engineered recombinant factor replacement (rFIX). Second-generation rFIX and monoclonal antibody solvents do not contain human plasma and are free of viral contaminants, including parvovirus B19.15

Etiology and Treatment

Gastrointestinal Bleeding

Sources of GI bleeding vary from hemorrhoids to Mallory-Weiss tears. The heterogeneous population of patients with GI bleeds complicates the identification of high-risk patients needing transfusion. Bleeding is traditionally characterized as either upper GI bleeding (UGIB) or lower GI bleeding (LGIB)—the former requiring endoscopy, the latter colonoscopy or other expensive strategies to differentiate one form from the other.

In patients with LGIB, the differential diagnosis is broad, ranging from hemorrhoidal bleeding, cancer, or life-threatening diverticular hemorrhage. Prompt volume replacement with isotonic crystalloid IV fluids must be initiated. In nonvariceal UGIB, blood transfusions should be initiated for Hgb levels <70g/L.16

Clinical prediction rules for acute GI bleeding can help identify those patients who require transfusions. One study collected data on seven established independent predictors of severe LGIB, including heart rate, systolic blood pressure (SBP), syncope, nontender abdomen, rectal bleeding in the first 4 hours of evaluation, aspirin use, and more than two comorbid conditions. A nontender abdomen was the best predictor of severe bleeding, likely due to the fact that vascular disorders, such as diverticulitis, result in brisk bleeding without tenderness; whereas inflammatory processes, such as ischemic colitis, are associated with less severe bleeding and abdominal tenderness. Patients with one or more of the seven risk factors were stratified into low (0-7 risk factors), moderate (1-3 risk factors), and high-risk groups (>3 risk factors). Low-risk patients had a ≤ 9% risk of a severe LGIB, moderate-risk patients had a 43% risk, and high-risk patients had >79% likelihood of bleeding. The high-risk patients were more likely to require early transfusion of PRBCs. Tachycardia, hypotension, syncope, nontender abdomen, and rectal bleeding were identified as the most significant predictors of patients requiring 4 or more units of PRBC in the first 24 hours. Such clinical prediction rules may aid in the initial triage of patients with acute LGIB and identify those most likely to require transfusion in the ED.17

 

 

Similar to LGIB transfusion prediction rules, the BLEED (ongoing bleeding, low systolic blood pressure, elevated prothrombin time [PT], erratic mental status, unstable comorbid disease) classification identified patients with UGIB most likely to require transfusion. High-risk patients had one or more of the following: ongoing bleeding, SBP <100 mm Hg, PT more than 1.2 times the control value, altered mental status, the presence of an unstable comorbid disease, or a disease process requiring management in the intensive care unit.18

Trauma

Within the first 48 hours of presentation, blood loss accounts for more than 50% of all trauma deaths.19,20 Posttraumatic bleeding is attributed to several factors, including vascular injury and coagulopathy. Hemodilution from large amounts of crystalloid infusion, hypothermia, and acidosis in early resuscitation adversely affect coagulation, platelet function, protein C consumption, and increases levels of tissue plasminogen activator inhibitor.21 A recent study comparing coagulation tests at the trauma scene and for 1 hour after injury, demonstrated significant activation and consumption of Factors V and XIII, fibrinogen, and proteins C and S.22 Patients with acute coagulopathy of trauma-shock (ACTS) were 4 times more likely to die than those without ACTS.22

In patients with evidence of hemorrhagic shock, hemodynamic instability, and inadequate oxygen (O2) delivery, a restrictive approach to transfusion is favored to maintain a goal hemoglobin of 7 to 9 g/dL. Generally, transfusion is considered when Hgb drops to <7 g/dL, especially in mechanically ventilated and other critically ill patients. Red blood cell transfusion should not be considered the singular or absolute method to improve tissue O2 consumption.23

Obstetric Hemorrhage

Postpartum hemorrhage (PPH) is a catastrophic maternal complication of delivery and a leading cause of maternal morbidity and mortality. Delayed hemorrhage may be seen in the ED days to weeks postpartum. Initial measures to control bleeding include uterine massage, uterotonic medications (ie, oxytocin), and blood-product components. Coagulopathy may be rapidly identified and FFP considered if a clot does not form within 7 minutes in a collection tube containing no anticoagulant (ie, red-top tube).12 During an ED delivery, uterine atony should be anticipated if the uterus is enlarged or the fundus is “doughy.” Atony is the most common cause of PPH within 24 hours and is managed with oxytocin 20 to 30 U/L at 200 mL/h. Alternatively, methylergonovine maleate 0.2 mg may be administered intramuscularly.24

Transfusion Complications

Several immediate complications may arise from transfusion, including intravascular hemolytic transfusion reactions, fever, urticaria, and transfusion-related lung injury (TRALI). Delayed complications include extravascular hemolytic reactions, and TA-GVHD. Other complications include acute bacteremia from contamination, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and transfusion-associated circulatory overload (TACO).

Intravascular Hemolytic Reactions

Intravascular hemolytic reactions resulting from ABO incompatibility are the most severe transfusion complication. Immediate onset symptoms include fever, chills, headache, nausea, vomiting, chest discomfort, and severe back pain. Treatment involves immediate cessation of the transfusion, replacement of all tubing components, and aggressive IV crystalloid fluid therapy with diuretics to maintain a urine output of 1 to 2 mL/kg/h. All remaining blood, along with the patient’s blood and urine samples, should be sent to the laboratory to detect free Hgb. A positive Coombs test on the posttransfusion blood confirms the diagnosis.

The most common reaction is a 1°C temperature elevation with no other cause. Treatment for fever and urticaria consists of antihistamines and antipyretics. However, febrile patients receiving blood for the first time should be managed as an intravascular hemolytic transfusion reaction until proved otherwise by a negative Coombs test. Mild reactions may be due to an allergic response to donor plasma proteins, but in patients with genetic immunoglobulin A (IgA) deficiency can represent an afebrile life-threatening reaction characterized by hypotension and respiratory symptoms. An IgA deficiency should be considered in patients of European descent as a cause of transfusion-related anaphylactic reactions.25

Transfusion-related Acute Lung Injury

The most common cause of mortality from transfusions is due to transfusion-related acute lung injury (TRALI), which presents within the first 6 hours of transfusion. Signs and symptoms of TRALI include noncardiogenic pulmonary edema, dyspnea, hypoxemia, fever, and hypotension. A portable chest X-ray may reveal bilateral infiltrates, and a complete blood count may demonstrate transient leukopenia. While the underlying mechanism is likely multifactorial, TRALI may be precipitated by a “leaky” pulmonary endothelium as a direct or indirect result of antibodies against the recipient. One strategy to reduce the incidence of TRALI is to use male donors for plasma to reduce the incidence of allotypic leukocyte antibodies that can occur in women who have had prior pregnancies. Management of TRALI includes immediately stopping the transfusion, notifying the blood bank, and providing respiratory support. Blood products may be transfused from a different donor. Unlike TACO or cardiogenic pulmonary edema, TRALI demonstrates no evidence of circulatory overload, and it does not respond to diuretic therapy.26 Circulatory overload may be avoided by infusing a single unit of PRBCs over 4 hours.

 

 

Extravascular Hemolytic Reactions

Delayed extravascular hemolytic reactions are most likely due to previous sensitization to red cell antigens from prior transfusion, pregnancy, or transplant. Extravascular hemolysis can occur days to weeks after repeat exposure. Patients present with fever, anemia, and jaundice without hemoglobinemia or hemoglobinuria. Symptoms are usually benign, though oliguria and DIC have been reported.27,28

Transfusion-associated graft-versus-host disease is a delayed extravascular hemolytic reaction that occurs in immunosuppressed recipients of transfused blood. Most deaths are due to coagulopathy or infection. Transfused lymphocytes proliferate and attack the blood recipient. Symptoms (eg, fever, rash, diarrhea, elevated liver transaminases, pancytopenia) begin 3 to 30 days posttransfusion, and a bone marrow transplant is indicated. Irradiated and leukoreduced blood components prevent TA-GVHD.29,30

Bacteremia and Viral Infection

Among significant bacterial contaminants from donor blood, Yersinia enterocolitica is the most common and has a mortality rate of greater than 50%.31 Typical symptoms include rigors, vomiting, abdominal cramps, fever, shock, renal failure, or DIC during transfusion. Immediate cessation of blood products and broad spectrum antibiotics are warranted. Risks among viral contaminants include human immunodeficiency disease (HIV), CMV, and hepatitis. Hepatitis B infection occurs in one in 1 million transfusion recipients, while the risk of hepatitis C is one in 1.2 million and HIV infection one in 1.5 million.32,33

Electrolyte Derangement

Electrolyte derangements after multiple-unit transfusions include hypocalcemia, hyperkalemia, and acid-base disorders. Massive blood transfusions with blood anticoagulated with sodium citrate and citric acid may contribute to metabolic alkalosis and hypocalcemia. Potassium may move into cells in exchange for hydrogen ions moving out of cells to minimize extracellular alkalosis, contributing to hypokalemia.34-36 To avoid hypocalcemia and alkalosis, the maximum citrate infusion rate should be 0.02 mmol/kg/minute, with the citrate concentration in whole blood measured as 15 mmol/L. If liver function is impaired in the setting of hypocalcemia-related blood transfusion, calcium chloride is preferred over calcium gluconate because it decreases citrate metabolism resulting in a slower release of ionized calcium.37 Calcium replacement should be considered in patients with liver dysfunction or patients with normal liver function who have received greater than 10 U pRBCs per hour. Calcium chloride (10%) is preferred over calcium gluconate to correct ionized hypocalcemia with 2 to 5 mL given for every 500mL of blood.37 Hyperkalemia risks are minimized by avoiding prolonged blood storage or irradiation.38

Conclusion

Timely administration of blood products is crucial in resuscitation and can be life-saving in a variety of bleeding disorders. Emergent reversal of warfarin therapy, correction of thrombocytopenia, bleeding due to hemophilia, GI bleeding, trauma, and obstetric hemorrhage are among the most common disorders managed in the ED. To select the most appropriate treatment, one must know the merits of the various blood products including PRBCs, platelets, FFP, and cryoprecipitate. The clinician must also be prepared to manage the immediate complications that may arise from transfusion including intravascular hemolytic reactions, fever, urticaria, and TRALI, as well as the delayed complications of extravascular hemolytic reactions, TA-GVHD, acute bacteremia, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and TACO.

Dr Stewart is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, Virginia, and Riverside Medical Group, Newport News, Virginia. Dr Devine is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, and Emergency Physicians of Tidewater, Norfolk, Virginia. The authors report no conflicts of interest.

References

  1. Napolitano LM, Kurek S, Luchette FA, et al; EAST Practice Management Workgroup; American College of Critical Care Medicine (ACCM) Taskforce of the Society of Critical Care Medicine (SCCM). Clinical Practice Guideline: Red Blood Cell Transfusion and Critical Care. J Trauma. 2009;67(6):1439-1442.
  2. Leal-Noval SR, Munoz-Gomez M, Jimenez-Sanchez M et al. Red blood cell transfusion in nonbleeding critically ill patients with moderate anemia: is there a benefit? Intensive Care Med. 2013;39(3):445-453.
  3. Carson JL, Grossman BJ, Kleinman S, et al; Clinical Transfusion Medicine Committee of the AABB. Red blood cell transfusion: a clinical practice guideline from the AAAB. Ann Intern Med. 2012;157(1):49-58.
  4. Gilliss BM, Looney MR, Gropper MA. Reducing noninfectious risks of blood transfusion. Anesthesiology. 2011;115(3):635-649.
  5. van Straaten HL, de Wildt-Eggen J, Huisveld IA. Evaluation of a strategy to limit blood donor exposure in high risk premature newborns based on clinical estimation of transfusion need. J Perniat Med. 2000;28(2):122-128.
  6. Anstee DJ. Red cell genotyping and the future of pretransfusion testing. Blood. 2009;114(2):248-256.
  7. Inaba K, Teixeira PG, Shulman I. The impact of uncross-matched blood transfusion on the need for massive transfusion and mortality: analysis of 5,166 uncross-matched units. J Trauma. 2008;65(6):1222-1226.
  8. Slichter SJ. Platelet transfusion therapy.  Hematol Oncol Clin North Am. 2007;21(4):697-729.
  9. Uppal P, Lodha R, Kabra SK. Transfusion of blood and components in critically ill children. Indian J Pediatr. 2010;77(12):1424-1428.
  10. Shah A, Stanworth SJ, McKechnie. Evidence and triggers for the transfusion of blood and blood products. Anesthesia. 2015;70(Suppl 1):10-19.
  11. Emery, M. Blood and Blood Components. In: Marx JA, Hockberger RS, Walls RM ed. Rosen’s emergency medicine: concepts and clinical practice. 7th ed. Philadelphia, PA: Mosby/Elsevier; 2009:42-46.
  12. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
  13. Santen S A Transfusion Therapy. In: Tintinalli, J. E., Kelen, G. D., & Stapczynski, J. S. ed. Emergency medicine: a comprehensive study guide. 6th ed. New York, NY: McGraw-Hill Medical; 20041349-1351.
  14. Osterman JL, Arora S. Blood product transfusions and reactions. Emerg Med Clin North Am. 2014;32(3): 727-738.
  15. Azzi A, De Santis R, Morfini M, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood. 2001;98(8):2571-2573.
  16. Barkun AN, Bardou M, Kuipers EJ, et al; International Consensus Upper Gastrointestinal Bleeding Conference Group International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101-113.
  17. Strate L, Saltzman J, and Ookubo R. Validation of a clinical prediction rule for severe acute lower intestinal bleeding. Am J Gastroenterol. 2005;100(8):1821-1827.
  18. Kollef MH, O’Brien JD, Zuckerman GR, Shannon W. BLEED: a classification tool to predict outcomes in patients with acute upper and lower gastrointestinal hemorrhage. Crit Care Med. 1997;25(7):1125-1132.
  19. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185-193.
  20. Simmons JW, Pittet JF, Pierce B. Trauma-induced coagulopathy. Curr Anesthisiol Rep. 2014;4(3):189-199.
  21. Zehtabchi S, Nishijima DK. Impact of transfusion of fresh-frozen plasma and packed red blood cells in a 1:1 ratio on survival of emergency department patients with severe trauma. Acad Emerg Med. 2009;16(5):371-378.
  22. Theusinger OM, Baulig W, Seifert B, Müller SM, Mariotti S, Spahn DR.. Changes in coagulation in standard laboratory tests and ROTEM in trauma patients between on-scene and arrival in the emergency department. Anesth Analg. 2014. [Epub ahead of print]
  23. Bouillon B, Brohi K, Hess JR, Holcomb JB, Parr MJ, Hoyt DB. Educational initiative on critical bleeding in trauma: Chicago, July 11-13, 2008. J Trauma. 2010;68(1):225-230.
  24. Phillips LE, McLintock C, Pollock W, et al; Australian and New Zealand Haemostasis Registry. Recombinant activated Factor VII in obstetric hemorrhage: experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg. 2009;109(6):1908-1915.
  25. Hirayama F. Current understanding of allergic transfusion reactions: incidence, pathogenesis, laboratory tests, prevention and treatment. Br J Haematol. 2013;160(4);434-444.
  26. Lieberman L, Maskens C, Cserti-Gazdewich C, 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)206-212.
  27. Welling KL, Taaning E, Lund BV, Rosenkvist J, Heslet L. Post-transfusion purpura (PTP) and disseminated intravascular coagulation (DIC). Eur J Haematol. 2003;71(1):68-71
  28. Kawai M, Takeda M, Tsugawa Y. Hemolytic anemia and acute renal failure caused by blood transfusions. Rinsho Ketusueki. 1990;31(10):1706-1710.
  29. Przepiorka D, LeParc GF, Stovall MA, Werch J, Lichtiger B. Use of irradiated blood components: practice parameter. Am J Clin Pathol. 1996;106(1):6-11.
  30. Rühl H, Bein G, Sachs UJ. Transfusion-associated graft-versus-host disease. Transfus Med Rev. 2009;23(1):62-71.
  31. Guinet F, Carniel E, Leclercq A. Transfusion-transmitted Yersinia enterolitica sepsis. Clin Infect Dis. 2011;53(6):583-591.
  32. Stramer SL, Notari EP, Krysztof DE, Dodd RY. Hepatitis B virus testing by minipool nuclear acid testing: does it improve blood safety? Transfusion. 2013; 53(10):2449-2458.
  33. Zou S, Stramer SL, Dodd RY. Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogenic donations. Transfus Med Rev. 2012;26(2):119-128.
  34. Dzik WH, Kirkley SA. Citrate toxicity during massive blood transfusion. Transfus Med Rev. 1988;2(2):76-94.
  35. Lier H, Krep H, Schroeder S, Stuber F. Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma. J Trauma. 2008;65(4):951-960.
  36. Bruining HA, Boelhouwer RU, Ong GK. Unexpected hypopotassemia after multiple blood transfusions during an operation. Neth J Surg. 1986;38(2):48-51.
  37. British Committee for Standards in Haematology; Stainsby D, MacLennan S, Thomas D, Isaac J, Hamilton PJ. Guidelines on the management of massive blood loss. Br J Haematol. 2006;135(5):634-641.
  38. Smith HM, Farrow SJ, Ackerman JD, Stubbs JR, Sprung J. Cardiac arrests associated with hyperkalemia during red blood cell transfusion: a case series. Anesth Analg. 2008;106(4):1062-1069.
References

  1. Napolitano LM, Kurek S, Luchette FA, et al; EAST Practice Management Workgroup; American College of Critical Care Medicine (ACCM) Taskforce of the Society of Critical Care Medicine (SCCM). Clinical Practice Guideline: Red Blood Cell Transfusion and Critical Care. J Trauma. 2009;67(6):1439-1442.
  2. Leal-Noval SR, Munoz-Gomez M, Jimenez-Sanchez M et al. Red blood cell transfusion in nonbleeding critically ill patients with moderate anemia: is there a benefit? Intensive Care Med. 2013;39(3):445-453.
  3. Carson JL, Grossman BJ, Kleinman S, et al; Clinical Transfusion Medicine Committee of the AABB. Red blood cell transfusion: a clinical practice guideline from the AAAB. Ann Intern Med. 2012;157(1):49-58.
  4. Gilliss BM, Looney MR, Gropper MA. Reducing noninfectious risks of blood transfusion. Anesthesiology. 2011;115(3):635-649.
  5. van Straaten HL, de Wildt-Eggen J, Huisveld IA. Evaluation of a strategy to limit blood donor exposure in high risk premature newborns based on clinical estimation of transfusion need. J Perniat Med. 2000;28(2):122-128.
  6. Anstee DJ. Red cell genotyping and the future of pretransfusion testing. Blood. 2009;114(2):248-256.
  7. Inaba K, Teixeira PG, Shulman I. The impact of uncross-matched blood transfusion on the need for massive transfusion and mortality: analysis of 5,166 uncross-matched units. J Trauma. 2008;65(6):1222-1226.
  8. Slichter SJ. Platelet transfusion therapy.  Hematol Oncol Clin North Am. 2007;21(4):697-729.
  9. Uppal P, Lodha R, Kabra SK. Transfusion of blood and components in critically ill children. Indian J Pediatr. 2010;77(12):1424-1428.
  10. Shah A, Stanworth SJ, McKechnie. Evidence and triggers for the transfusion of blood and blood products. Anesthesia. 2015;70(Suppl 1):10-19.
  11. Emery, M. Blood and Blood Components. In: Marx JA, Hockberger RS, Walls RM ed. Rosen’s emergency medicine: concepts and clinical practice. 7th ed. Philadelphia, PA: Mosby/Elsevier; 2009:42-46.
  12. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
  13. Santen S A Transfusion Therapy. In: Tintinalli, J. E., Kelen, G. D., & Stapczynski, J. S. ed. Emergency medicine: a comprehensive study guide. 6th ed. New York, NY: McGraw-Hill Medical; 20041349-1351.
  14. Osterman JL, Arora S. Blood product transfusions and reactions. Emerg Med Clin North Am. 2014;32(3): 727-738.
  15. Azzi A, De Santis R, Morfini M, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood. 2001;98(8):2571-2573.
  16. Barkun AN, Bardou M, Kuipers EJ, et al; International Consensus Upper Gastrointestinal Bleeding Conference Group International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101-113.
  17. Strate L, Saltzman J, and Ookubo R. Validation of a clinical prediction rule for severe acute lower intestinal bleeding. Am J Gastroenterol. 2005;100(8):1821-1827.
  18. Kollef MH, O’Brien JD, Zuckerman GR, Shannon W. BLEED: a classification tool to predict outcomes in patients with acute upper and lower gastrointestinal hemorrhage. Crit Care Med. 1997;25(7):1125-1132.
  19. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185-193.
  20. Simmons JW, Pittet JF, Pierce B. Trauma-induced coagulopathy. Curr Anesthisiol Rep. 2014;4(3):189-199.
  21. Zehtabchi S, Nishijima DK. Impact of transfusion of fresh-frozen plasma and packed red blood cells in a 1:1 ratio on survival of emergency department patients with severe trauma. Acad Emerg Med. 2009;16(5):371-378.
  22. Theusinger OM, Baulig W, Seifert B, Müller SM, Mariotti S, Spahn DR.. Changes in coagulation in standard laboratory tests and ROTEM in trauma patients between on-scene and arrival in the emergency department. Anesth Analg. 2014. [Epub ahead of print]
  23. Bouillon B, Brohi K, Hess JR, Holcomb JB, Parr MJ, Hoyt DB. Educational initiative on critical bleeding in trauma: Chicago, July 11-13, 2008. J Trauma. 2010;68(1):225-230.
  24. Phillips LE, McLintock C, Pollock W, et al; Australian and New Zealand Haemostasis Registry. Recombinant activated Factor VII in obstetric hemorrhage: experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg. 2009;109(6):1908-1915.
  25. Hirayama F. Current understanding of allergic transfusion reactions: incidence, pathogenesis, laboratory tests, prevention and treatment. Br J Haematol. 2013;160(4);434-444.
  26. Lieberman L, Maskens C, Cserti-Gazdewich C, 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)206-212.
  27. Welling KL, Taaning E, Lund BV, Rosenkvist J, Heslet L. Post-transfusion purpura (PTP) and disseminated intravascular coagulation (DIC). Eur J Haematol. 2003;71(1):68-71
  28. Kawai M, Takeda M, Tsugawa Y. Hemolytic anemia and acute renal failure caused by blood transfusions. Rinsho Ketusueki. 1990;31(10):1706-1710.
  29. Przepiorka D, LeParc GF, Stovall MA, Werch J, Lichtiger B. Use of irradiated blood components: practice parameter. Am J Clin Pathol. 1996;106(1):6-11.
  30. Rühl H, Bein G, Sachs UJ. Transfusion-associated graft-versus-host disease. Transfus Med Rev. 2009;23(1):62-71.
  31. Guinet F, Carniel E, Leclercq A. Transfusion-transmitted Yersinia enterolitica sepsis. Clin Infect Dis. 2011;53(6):583-591.
  32. Stramer SL, Notari EP, Krysztof DE, Dodd RY. Hepatitis B virus testing by minipool nuclear acid testing: does it improve blood safety? Transfusion. 2013; 53(10):2449-2458.
  33. Zou S, Stramer SL, Dodd RY. Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogenic donations. Transfus Med Rev. 2012;26(2):119-128.
  34. Dzik WH, Kirkley SA. Citrate toxicity during massive blood transfusion. Transfus Med Rev. 1988;2(2):76-94.
  35. Lier H, Krep H, Schroeder S, Stuber F. Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma. J Trauma. 2008;65(4):951-960.
  36. Bruining HA, Boelhouwer RU, Ong GK. Unexpected hypopotassemia after multiple blood transfusions during an operation. Neth J Surg. 1986;38(2):48-51.
  37. British Committee for Standards in Haematology; Stainsby D, MacLennan S, Thomas D, Isaac J, Hamilton PJ. Guidelines on the management of massive blood loss. Br J Haematol. 2006;135(5):634-641.
  38. Smith HM, Farrow SJ, Ackerman JD, Stubbs JR, Sprung J. Cardiac arrests associated with hyperkalemia during red blood cell transfusion: a case series. Anesth Analg. 2008;106(4):1062-1069.
Issue
Emergency Medicine - 47(2)
Issue
Emergency Medicine - 47(2)
Page Number
77-84
Page Number
77-84
Publications
Emergency Medicine
MDedge Emergency Medicine
Publications
Emergency Medicine
MDedge Emergency Medicine
Topics
Imaging
Hematology
Gastroenterology
Trauma
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Article
Display Headline
Blood Product Selection and Administration
Display Headline
Blood Product Selection and Administration
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