Updated: Jul 2, 2008
Patients with acute blood loss or symptomatic anemia frequently require blood replacement therapy in the emergency department (ED). Although blood replacement therapy is generally safe, it should be understood that certain risks accompany the transfusion of blood and plasma components. Accordingly, emergency physicians must be familiar with and be able to manage adverse transfusion reactions, ranging from self-limited febrile responses to life-threatening intravascular hemolysis.
Hemolytic transfusion reactions
Hemolytic transfusion reactions are the result of antibodies in the recipient's plasma directed against antigens on the donor's erythrocytes. This results in rapid intravascular hemolysis of the donor red blood cells. ABO incompatibility due to clerical error is the most frequent cause. This results in hemoglobinemia, hemoglobinuria, disseminated intravascular coagulation (DIC), renal failure, and complement-mediated cardiovascular collapse.
The recipient's antibodies to Rh or non-ABO antigens cause extravascular hemolytic reactions. These patients usually have been exposed to the antigen through previous pregnancies, transplantation, or transfusions. Antibody titers often are too low to be detected through routine antibody screening, but production of antibodies becomes amplified with reexposure. These antibodies do not activate complement; therefore, no intravascular hemolysis occurs. Instead, the RBCs are tagged for removal by splenic macrophages.
Nonhemolytic febrile reactions
Nonhemolytic febrile reactions are thought to stem from the formation of cytokines during the storage of the blood. These reactions seldom proceed to hypotension or respiratory distress.
Anaphylactic reactions
Anaphylactic reactions most often are observed in those patients with a hereditary immunoglobulin A (IgA) deficiency. Some of these patients have developed complement-binding anti-IgA antibodies that cause anaphylaxis when exposed to donor IgA.
Proteins in the donor plasma can cause minor allergic reactions. This is an anaphylactoid reaction and is observed more frequently with components containing large amounts of plasma, such as whole blood, pooled platelets, and fresh frozen plasma.
Acquired diseases
Infectious diseases also may be transmitted through transfusion.
Graft-versus-host disease
Graft-versus-host (GVH) disease occurs when donor lymphocytes mount an immune response against the recipient's lymphoid tissue. Normally, the donor lymphocytes are recognized as being foreign and are destroyed. In situations when the donor is immunocompromised or when the donor is homozygous and the recipient is heterozygous for an HLA haplotype, these normal defense mechanisms may fail, resulting in GVH disease.
Transfusion-related acute lung injury
Transfusion-related acute lung injury may be caused by transfusing any plasma-containing blood product. It is caused by the interaction between the recipient's leukocytes and preexisting donor antileukocyte antibodies. This results in complement activation and increased pulmonary vascular permeability. In addition, mediators of inflammation that form while the blood is in storage are also felt to be contributory.
Massive transfusion complications
Massive transfusion is defined as the replacement of more than one-half of the blood volume within a 24-hour period or the replacement of 10 units of blood over the course of a few hours. Complications of massive transfusion include the following:
Hemolytic transfusion reactions result in death in 1 per 100,000 units transfused.
Nonhemolytic febrile reactions and extravascular hemolytic reactions are more common in parous females.
Children have a greater risk of developing transfusion-related HIV than adults.
| Acute Respiratory Distress Syndrome | Hypokalemia |
| Anaphylaxis | Hypothermia |
| Congestive Heart Failure and Pulmonary
Edema | Rh Incompatibility |
| Disseminated Intravascular Coagulation | Toxic Epidermal Necrolysis |
| Hyperkalemia | Toxicity, Ethylene Glycol |
| Hypocalcemia | Urticaria |
Allergic reaction
Fever
Hemolysis
Sepsis
All patients receiving blood products should be placed on continuous cardiac monitoring and pulse oximetry.
In hemolytic transfusion reactions, pharmacologic treatment is aimed at increasing renal blood flow and preserving urinary output. In anaphylaxis, the goals of therapy are to maintain hemodynamic stability and reverse the underlying process.
These agents are used to increase renal blood flow and preserve urinary output in hemolytic transfusion reactions. They also may be used in transfusion-related volume overload.
Increases excretion of water by interfering with chloride-binding cotransport system, which results in inhibition of sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Individualize dose to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs.
20-40 mg/d IV/IM
Infants: Titrate with 1 mg/kg/dose IV increments until satisfactory effect achieved
Children: 1-2 mg/kg/dose PO/IV/IM; not to exceed 6 mg/kg/dose; do not administer more frequently than q6h
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; aminoglycosides increase auditory toxicity, hearing loss of varying degrees may occur; may enhance anticoagulant activity of warfarin; may increase plasma lithium levels and toxicity
Documented hypersensitivity; hepatic coma; anuria; severe electrolyte depletion
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter
These agents are used to increase renal blood flow and preserve urinary output in hemolytic transfusion reactions. In severe allergic reactions, epinephrine is used for its inotropic properties and ability to maintain perfusion of vital organs.
Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect depends on dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.
1-5 mcg/kg/min IV; after initiating therapy, dose may be increased by 1-4 mcg/kg/min IV q10-30min until satisfactory response attained; maintenance doses <20 mcg/kg/min usually satisfactory for 50% of treated patients
Administer as in adults
Phenytoin, alpha- and beta-adrenergic blockers, general anesthetics, and MAOIs increase and prolong effects
Documented hypersensitivity, pheochromocytoma; ventricular fibrillation
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and BP during infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia
DOC for treating anaphylaxis. Stimulates alpha-, beta1, and beta2-adrenergic receptors, which in turn results in bronchodilatation, increased peripheral vascular resistance, hypertension, increased chronotropic cardiac activity, and positive inotropic effects.
0.01 mL/kg of 1:1000 solution IM/SC initially; not to exceed 0.5 mL of 1:1000 solution (0.5 mg) IM/SC
Severe anaphylaxis: 10 mL of 1:100,000 dilution of aqueous epinephrine IV over 10 min
With no improvement, establish 1 mcg/min continuous IV infusion of 4 mcg/mL concentration; increase to 4 mcg/min prn
0.1 mcg/kg/min SC q15min for 2 doses then q4h with increments of 0.1 mcg/kg/min prn; not to exceed 1.5 mcg/kg/min
Increases toxicity of beta- and alpha-blocking agents and of halogenated inhalational anesthetics
Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma; concurrent use with local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (can delay second stage of labor)
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Caution with elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias
Used to treat minor allergic reactions and anaphylaxis. Diphenhydramine may be used to pretreat patients with prior documentation of minor allergic reactions.
Used for symptomatic relief of allergic symptoms caused by histamine released in response to allergens.
25-50 mg PO q6-8h prn; not to exceed 400 mg/d
10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d
12.5-25 mg PO tid/qid or 5 mg/kg/d PO or 150 mg/m2/d PO divided tid/qid; not to exceed 300 mg/d
5 mg/kg/d or 150 mg/m2/d IV/IM divided qid; not to exceed 300 mg/d
Potentiates effect of CNS depressants; due to alcohol content, do not administer syrup dosage form to patients taking medications that can cause disulfiram reactions
Documented hypersensitivity; MAOIs
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction
H2 antagonist that, when combined with H1 type, may be useful in treating itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis that do not respond to H1 antagonists alone. Use in addition to H1 antihistamines.
300 mg IV; when clinically possible, PO q6h for 2 d or for as long as clinically indicated
<16 years: 25-30 mg/kg/d IV in 6 divided doses; administer only if benefits outweigh risks
>16 years: 25-30 mg/kg/d IV in 6 divided doses
Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Documented hypersensitivity
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Elderly may suffer confusional states; may cause impotence and gynecomastia in young males due to weak antiandrogen properties; may increase levels of many drugs; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
These agents have limited benefit in the initial acute treatment of rapidly deteriorating anaphylactic patient. However, they may benefit patients with persistent bronchospasm or hypotension. Onset of action is approximately 4-6 h following its administration.
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Useful in treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.
125-250 mg IV loading dose; followed by 0.5-1 mg/kg/dose q6h for up to 5 d
2 mg/kg IV initially; followed by 0.5-1 mg/kg/dose q6h for up to 5 d
Estrogens may decrease clearance; may increase digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor patients for hypokalemia with concurrent use of diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, infections
Stainsby D, MacLennan S, Thomas D, Isaac J, Hamilton PJ. Guidelines on the management of massive blood loss. Br J Haematol. Dec 2006;135(5):634-41. [Medline].
Cherry T, Steciuk M, Reddy VV, Marques MB. Transfusion-related acute lung injury: past, present, and future. Am J Clin Pathol. Feb 2008;129(2):287-97. [Medline].
Dellinger EP, Anaya DA. Infectious and immunologic consequences of blood transfusion. Crit Care. 2004;8 Suppl 2:S18-23. [Medline].
Dodd RY, Leiby DA. Emerging infectious threats to the blood supply. Annu Rev Med. 2004;55:191-207. [Medline].
Fiebig EW, Busch MP. Emerging infections in transfusion medicine. Clin Lab Med. Sep 2004;24(3):797-823, viii. [Medline].
Goodnough LT. Risks of blood transfusion. Anesthesiol Clin North America. Jun 2005;23(2):241-52, v. [Medline].
Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury: a review. Chest. Jul 2004;126(1):249-58. [Medline].
Spahn DR, Rossaint R. Coagulopathy and blood component transfusion in trauma. Br J Anaesth. Aug 2005;95(2):130-9. [Medline].
Stainsby D, Russell J, Cohen H, Lilleyman J. Reducing adverse events in blood transfusion. Br J Haematol. Oct 2005;131(1):8-12. [Medline].
Williams AE, Thomson RA, Schreiber GB, et al. Estimates of infectious disease risk factors in US blood donors. Retrovirus Epidemiology Donor Study. JAMA. Mar 26 1997;277(12):967-72. [Medline].
transfusion reaction, hemolytic transfusion reactions, nonhemolytic febrile reactions, anaphylactic reactions, graft-versus-host disease, GVH disease, massive transfusion complications, transfusion-related hepatitis C, chronic hepatitis, cirrhosis, blood replacement, symptomatic anemia, acute blood loss, blood transfusion, transfusion-related acute lung injury
Eric Kardon, MD, FACEP, Associate Staff, Division of Emergency Medicine, Athens Regional Medical Center
Eric Kardon, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
Theodore J Gaeta, DO, MPH, FACEP, Clinical Associate Professor, Department of Emergency Medicine, Joan and Sanford Weill Medical College at Cornell University; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine
Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, New York Academy of Medicine, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.
John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School
Jonathan Adler, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: eMedicine.com, Inc. Consulting fee Consulting
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