Transfusion Reactions


Article Author:
Jolee Suddock


Article Editor:
Kendall Crookston


Editors In Chief:
Chaddie Doerr


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
2/6/2019 12:05:21 PM

Introduction

Transfusion reactions are defined as adverse events associated with the transfusion of whole blood or one of its components. These may range in severity from minor to life-threatening. Reactions can occur during the transfusion (acute transfusion reactions) or days to weeks later (delayed transfusion reactions) and may be immunologic or non-immunologic. A reaction may be difficult to diagnose as it can present with non-specific, often overlapping symptoms. The most common signs and symptoms include fever, chills, urticaria (hives), and itching. Some symptoms resolve with little or no treatment. However, respiratory distress, high fever, hypotension (low blood pressure), and red urine (hemoglobinuria) can indicate a more serious reaction.

Types of transfusion reactions include the following: acute hemolytic, delayed hemolytic, febrile non-hemolytic, anaphylactic, simple allergic, septic (bacterial contamination), transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO). All suspected reactions should result in immediately stopping the transfusion and notifying the blood bank and treating clinician.[1][2][3]

Etiology

Immune-mediated transfusion reactions typically occur due to mismatch or incompatibility of the transfused product and the recipient. They include naturally occurring antibodies in the blood recipient (such as anti-A, anti-B which are typically responsible for acute hemolytic transfusion reactions) as well as antibodies made in response to foreign antigens (alloantibodies). These alloantibodies account for many reactions including mild allergic, febrile non-hemolytic, acute hemolytic and anaphylactic. Antibodies present in the blood donor can also cause reactions and are thought to be involved in transfusion-associated lung injury (TRALI).[4][5][6]

Non-immunologic reactions are usually caused by the physical effects of blood components or the transmission of disease. Bacterial contamination, for example, results in septic transfusion reactions and is caused by bacterial and/or endotoxin contamination of a blood product. This may happen at the time of collection due to inadequate blood donor arm disinfection, the presence of bacteria in the donor’s circulation at the time of collection, or due to improper product handling after collection.

Transfusion reactions can also occur unrelated to factors intrinsic to the blood. Examples of these include transfusion-associated volume overload (TACO) and hypothermia.

Epidemiology

Transfusion reactions range in frequency from relatively common, (mild allergic and febrile non-hemolytic reactions) to rare (anaphylaxis, acute hemolytic, and sepsis). Fatal adverse events have been reported to occur most commonly with TRALI, and long-term or later adverse events are typically the result of disease transmission.

The severity and incidence vary depending on the type of transfusion reaction, the prevalence of disease in the donor population, and the extent of follow-up care the patient receives. Due to advances in donor screening, improved testing, and automated data systems, the risks and fatalities associated with the transfusion of blood products continue to decrease.[7][8]

Pathophysiology

The pathophysiology varies based on the transfusion reaction.[9][10][11]

Acute Transfusion Reactions

  • Mild allergic: Attributed to hypersensitivity to a foreign protein in the donor product.
  • Anaphylactic: Similar to a mild allergic reaction, however resulting in a more severe reaction. Sometimes this can occur in a patient with IgA deficiency who makes alloantibodies against IgA and then receives blood products containing IgA.
  • Febrile non-hemolytic: Generally thought to be caused by cytokines released from blood donor leukocytes (white blood cells).
  • Septic: Caused by bacteria or bacterial byproducts (such as endotoxin) which may contaminate blood.
  • Acute hemolytic transfusion reactions: Can result in intravascular or extravascular hemolysis, depending on the specific etiology (cause). Immune-mediated reactions are often a result of recipient antibodies present to blood donor antigens. Non-immune reactions are possible, and occur when red blood cells are damaged before transfusion (e.g., by heat or incorrect osmotic conditions).
  • Transfusion-associated circulatory overload (TACO): Occurs when the volume of the transfused component causes hypervolemia (volume overload).
  • Transfusion-related acute lung injury: Acute lung injury is due to antibodies in the donor product (human leukocyte antigen or human neutrophil antigen) reacting with antigens in the recipient. The recipient’s immune system responds and causes the release of mediators that lead to pulmonary edema. Possibly contributing to this are clinical conditions that predispose the patient including infection, recent surgery, or inflammation.

Delayed Transfusion Reactions

  • Delayed hemolytic transfusion reaction: Typically caused by an anamnestic response to a foreign antigen that the patient was previously exposed to (generally by prior transfusion or pregnancy).
  • Transfusion-associated graft-versus-host disease: Results from engraftment of donor lymphocytes (commonly found in cellular blood products) into an immunocompromised recipient’s bone marrow. The donor lymphocytes recognize the patient as foreign and react against the recipient’s body. The patient’s immune system is unable to clear the foreign lymphocytes. This is rare but often fatal.

History and Physical

A thorough understanding of the patient’s medical history and state of health is needed before the transfusion is started. Vital signs are monitored and typically recorded at 15-minute intervals. A small amount of change in vital signs during transfusion may be considered “normal.”  These changes may include the following: plus or minus 0.5 C in temperature, plus or minus 5 respirations per minute, plus or minus 10 beats per minute in heart rate, and plus or minus 20 mm Hg in blood pressure.  It is important to note that changes greater than these parameters do not mean that there is a transfusion reaction, it suggests that the bedside nurse should be extra vigilant in monitoring for a reaction. Abnormal responses include hives, itching, fever greater than 1 C above the temperature at the start of transfusion, chills, hypotension, and dyspnea.

Evaluation

Diagnosis of acute transfusion reactions begins by recognition of the signs and symptoms by the bedside. Common signs and symptoms and differential diagnosis are listed below.[12][13][14]

  • Urticaria/Itching

Urticaria (hives) and/or itching can be the presenting sign of a mild allergic reaction, but can also be associated with the onset of a life-threatening anaphylactic reaction. The transfusion should be stopped, and the patient should be carefully monitored for progression of symptoms.

  • Fever/Chills

Fever and/or chills are most commonly associated with a febrile, non-hemolytic reaction, however; they can also be the first sign of a more serious acute hemolytic reaction, TRALI, or septic transfusion reaction. If the temperature rises 1 C or higher from the temperature at the start of transfusion, the transfusion should be stopped. Acute hemolytic reaction or bacterial contamination should be suspected if there is a greater rise in temperature, or more serious symptoms (e.g., rigors).

  • Respiratory Distress/Dyspnea

Dyspnea, or shortness of breath, is a concerning sign that can often be seen with more severe reactions including anaphylaxis, TRALI, and TACO. It can also be seen by itself without accompanying symptoms.

  • Hypotension

Hypotension can be seen with an acute hemolytic reaction, septic transfusion reactions, anaphylaxis, and TRALI. They have also been reported without the presence of any other associated transfusion reaction.

  • Hypothermia

Hypothermia can be seen with large volume transfusions of refrigerated products. The only intervention needed is warming the patient and/or blood product.

Treatment / Management

When a transfusion reaction is suspected, the transfusion should be immediately stopped, and the intravenous line should be kept open using appropriate fluids (usually 0.9% saline). A clerical check should be performed by examining the product bag and confirming the patient’s identification. The patient’s vital signs should be monitored and recorded at 15-minute intervals. A post-transfusion blood sample should be drawn and sent to the lab, in addition to sending the bag and tubing if possible. The blood bank generally completes additional testing and clerical checks to rule out an incompatible transfusion.

Treatment of specific transfusion reactions is most often supportive. For example, antihistamines (such as diphenhydramine) can be given for a mild allergic reaction, or an antipyretic can be given for a non-hemolytic febrile transfusion reaction.[9][15]

Differential Diagnosis

  • Anaphylaxis
  • Disseminated intravascular coagulation
  • Hemolytic anemia
  • Septic shock

Complications

  • Disseminated intravascular coagulation
  • Lung injury
  • Renal failure
  • Hemolysis
  • Death

Pearls and Other Issues

Transfusion reactions are influenced by many factors including the type of component being transfused, the storage requirements, and the patient’s co-morbid conditions at the time of transfusion. Understanding how to quickly identify transfusion reactions and appropriately manage and treat the patient ensures optimal patient care.

Enhancing Healthcare Team Outcomes

Blood transfusions are often necessary in medicine, and all healthcare workers have to be familiar with transfusion reactions. Patient on any ward can receive a blood transfusion and similarly all nurses have to know the potential complications and how to manage them. The majority of blood transfusion reactions occur because of a clerical/nursing error. While some reactions can be severe and lead to death, many transfusion reactions are benign. Anaphylactic reactions from a blood transfusion are very rare but often result in a fatality. Other reactions include TRALI which ranges from 1-9% and often requires intensive pulmonary support to prevent a fatal outcome. The incidence of bacterial contamination is rare but can occur from both gram-negative and gram-positive organisms. The key to reducing the morbidity is vigilance on the part of the nurse. During the patient medical history, one should ask about prior transfusions and any complications. If there is ever any doubt about the patient's blood group or the blood type being administered, the laboratory should be asked to reconfirm the status.[16][17] (Level V)

 


  • Image 6126 Not availableImage 6126 Not available
    Kendall Crookston MD PhD Professor, Pathology and Medicine University of New Mexico School of Medicine
Attributed To: Kendall Crookston MD PhD Professor, Pathology and Medicine University of New Mexico School of Medicine

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Transfusion Reactions - Questions

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Which intervention is least important in the management of a hemolytic transfusion reaction?



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Which is false about a blood transfusion hemolytic reaction?



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Which of the following is false about fevers caused during a blood transfusion?



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Which is not a manifestation of a blood transfusion reaction?



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In addition to discontinuing the transfusion, how should a patient suspected of having a hemolytic transfusion reaction be managed?



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A group A recipient has mistakenly received a unit of group B blood. Which of the following is not a transfusion-mediated reaction symptom?



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In a patient who repeatedly develops a fever following blood transfusions with leukoreduced red blood cells (RBCs), what is the most appropriate measure?



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In a patient who has suffered an acute hemolytic reaction, which of the following is not an early sign?



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Transfusion of red blood cells in a trauma patient results in immediate hypotension, hematuria, and fever. Which of the following is not part of the management of this patient?



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A 27-year-old trauma patient is taken to the operating room (OR) for a massive liver injury, requiring four units of packed red blood cells in the first hour of surgery. While in the OR he becomes hypotensive, oliguric, and febrile. His central venous pressure is 6 cmH2O. What is the most likely diagnosis?



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A 70-year-old undergoes elective colon surgery. During surgery, he is administered two units of blood. Four days later, he develops a fever and his serum bilirubin is elevated. The direct Coombs test is now positive. He most likely has which condition?



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Which would be the best treatment for a transfusion related hemolytic reaction?



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A 35-year-old with a history of alcoholism is admitted for an acute upper GI bleed. He is given four units of packed red blood cells. He undergoes urgent endoscopic repair of his bleeding esophageal varices. On hospital day seven, he develops jaundice and become oliguric. Serum creatinine is 2.9 and urine has the presence of red blood cells, pigmented casts, but no bilirubin or crystals. Liver function tests are normal. What is the next best step?



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What is the initial treatment for a patient with a hemolytic transfusion reaction?



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What is the most common complication after blood transfusion?



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A 26-year-old male is resuscitated with blood transfusion after a motor vehicle collision that was complicated by a fractured pelvis. A few hours later, the patient becomes febrile, hypotensive with a normal CVP, and oliguric. Upon examination, the patient is found to be bleeding from the NG tube and IV sites. Which of the following is the most likely diagnosis?



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A 33-year-old man is suspected of having developed a transfusion reaction during resuscitation after pelvic trauma. Which of the following is appropriate in the management of this patient?



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A patient with a history of recurrent sinusitis has an allergic reaction after a transfusion with cross-matched blood. Which of the following is the most likely cause?



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A patient is to receive a transfusion with packed red blood cells. Within a few minutes of starting the blood, the patient develops pruritus and hives. Select the best initial intervention.



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An open-heart surgery patient who had an uneventful two-vessel bypass continues to have minor bleeding during closure and is given packed red blood cells rapidly to maintain volume. Soon after he develops renal failure, hypotension, and diffuse bleeding from the incision and suture lines. What is the most likely diagnosis?



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What is the most common cause of mortality following a blood transfusion based on data released by the Center for Disease Control and Prevention?



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Which of the following is an approach to decrease the risk of an allergic transfusion reaction?



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What is the most common cause of an acute hemolytic transfusion reaction?



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What steps that should be followed when a transfusion reaction is suspected?



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A patient receiving a blood transfusion has developed urticaria. What is the first step should be taken?



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Transfusion Reactions - References

References

Sirianni G,Perri G,Callum J,Gardner S,Berall A,Selby D, A Retrospective Chart Review of Transfusion Practices in the Palliative Care Unit Setting. The American journal of hospice     [PubMed]
McClosky ME,Cimino Brown D,Weinstein NM,Chappini N,Taney MT,Marryott K,Callan MB, Prevalence of naturally occurring non-AB blood type incompatibilities in cats and influence of crossmatch on transfusion outcomes. Journal of veterinary internal medicine. 2018 Oct 11     [PubMed]
Land KJ,Townsend M,Goldman M,Whitaker BI,Perez GE,Wiersum-Osselton JC, International validation of harmonized definitions for complications of blood donations. Transfusion. 2018 Oct 8     [PubMed]
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Jasinski S,Glasser CL, Catastrophic Delayed Hemolytic Transfusion Reaction in a Patient With Sickle Cell Disease Without Alloantibodies: Case Report and Review of Literature. Journal of pediatric hematology/oncology. 2018 Aug 31     [PubMed]
Erony SM,Marshall CE,Gehrie EA,Boyd JS,Ness PM,Tobian AAR,Carroll KC,Blagg L,Shifflett L,Bloch EM, The epidemiology of bacterial culture-positive and septic transfusion reactions at a large tertiary academic center: 2009 to 2016. Transfusion. 2018 Aug     [PubMed]
Py JY,Cabezon B,Sapey T,Jutant T, Unacknowledged adverse transfusion reactions: Are they a mine to dig? Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2018 Feb     [PubMed]
Jacquot C,Delaney M, Efforts Toward Elimination of Infectious Agents in Blood Products. Journal of intensive care medicine. 2018 Oct     [PubMed]
Siddon AJ,Kenney BC,Hendrickson JE,Tormey CA, Delayed haemolytic and serologic transfusion reactions: pathophysiology, treatment and prevention. Current opinion in hematology. 2018 Nov     [PubMed]
Tariket S,Sut C,Hamzeh-Cognasse H,Laradi S,Garraud O,Cognasse F, Platelet and TRALI: From blood component to organism. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2018 Sep     [PubMed]
Scher CS, Trauma and transfusion in the geriatric patient. Current opinion in anaesthesiology. 2018 Apr     [PubMed]
Garraud O,Cognasse F,Laradi S,Hamzeh-Cognasse H,Peyrard T,Tissot JD,Fontana S, How to mitigate the risk of inducing transfusion-associated adverse reactions. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2018 Nov     [PubMed]
Fasano RM,Meyer EK,Branscomb J,White MS,Gibson RW,Eckman JR, Impact of Red Blood Cell Antigen Matching on Alloimmunization and Transfusion Complications in Patients with Sickle Cell Disease: A Systematic Review. Transfusion medicine reviews. 2018 Jul 26     [PubMed]
Strasser E, [The new hemotherapy guideline]. Der Unfallchirurg. 2018 May     [PubMed]
Long B,Koyfman A, Emergency Medicine Evaluation and Management of Anemia. Emergency medicine clinics of North America. 2018 Aug     [PubMed]
Carman M,Uhlenbrock JS,McClintock SM, CE: A Review of Current Practice in Transfusion Therapy. The American journal of nursing. 2018 May     [PubMed]
DeLisle J, Is This a Blood Transfusion Reaction? Don't Hesitate; Check It Out. Journal of infusion nursing : the official publication of the Infusion Nurses Society. 2018 Jan/Feb     [PubMed]

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