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Transfusion Reaction

Blood Transfusion Reactions

Transfusion reaction is a general term to describe any adverse reaction of the immune system of a patient after receiving blood products.


Presentation

The clinical picture varies with the underlying TR.

While acute hemolytic TR are often characterized by fever and chills, flushing, hypotension, in severe cases dyspnea and hemoglobinuria, an allergic TR manifests without fever. In patients suffering from hypersensitivity, the most striking signs are urticaria and pruritus; flushing, hypotension, dyspnea and anxiety may be detected and may indicate imminent anaphylaxis and bronchospasm.

Febrile non-hemolytic TR are associated with fever and generally no other symptoms. However, chills, hypotension and vomiting have been occasionally observed.

TRALI symptoms are dyspnea, rales, hypoxemia, tachycardia and fever. Onset is fast; patients do not present any symptoms indicating cardiac insufficiency to account for pulmonary edema.

It is important to note that patients receiving blood transfusions are sometimes in poor overall condition and may present different comorbidities. Thus, a rapid deterioration of the patient's health may not necessarily be triggered by the current or past transfusion. This may merely be a coincidence, although it may not be a very likely one. Health care givers should consider this possibility when trying to identify the source of the problem.

Fever
  • While acute hemolytic TR are often characterized by fever and chills, flushing, hypotension, in severe cases dyspnea and hemoglobinuria, an allergic TR manifests without fever.[symptoma.com]
  • Abstract We report on the case of a woman who suffered from chills and fever when she was transfused with two units of red blood cell concentrate.[ncbi.nlm.nih.gov]
  • Classic SX: abrupt onset of acute flank pain, bright red urine, fever, and often a patient's complaint that "something is wrong." Fever (body temperature elevation of greater than 1 C above normal) and chills are commonly seen.[enotes.tripod.com]
  • BACKGROUND: A patient with B sickle cell disease received 3 units of red blood cells (RBCs) from two O donors and developed fever and hypotension after the first unit, consistent with an acute transfusion reaction (ATR).[ncbi.nlm.nih.gov]
  • Mean interval from RBC transfusion to DHTR event was 10·1 5·4 d, and typical presenting features were fever, pain and haemoglobinuria. Twenty of the 23 (87·0%) DHTR episodes occurred following transfusion in the acute setting.[ncbi.nlm.nih.gov]
Chills
  • Abstract We report on the case of a woman who suffered from chills and fever when she was transfused with two units of red blood cell concentrate.[ncbi.nlm.nih.gov]
  • BACKGROUND AND OBJECTIVES: Febrile non-haemolytic transfusion reaction (FNHTR) is an acute transfusion complication resulting in fever, chills and/or rigours.[ncbi.nlm.nih.gov]
  • Fever (body temperature elevation of greater than 1 C above normal) and chills are commonly seen.[enotes.tripod.com]
  • Fever, chills and urticaria are the most common manifestations of transfusion reactions.[transfusion.com.au]
  • However, chills, hypotension and vomiting have been occasionally observed. TRALI symptoms are dyspnea, rales, hypoxemia, tachycardia and fever.[symptoma.com]
Rigor
  • We report an acute HTR due to anti-Wr(a) in a 58-year-old man with myelodysplastic syndrome associated with rigors, shortness of breath and a significant rise in serum bilirubin from 16 micromol L(-1) pretransfusion to 110 micromol L(-1) immediately afterwards[ncbi.nlm.nih.gov]
  • In case of non-antibody mediated AHR This does not require rigorous management.[en.wikipedia.org]
  • […] transfusing plasma from males in order to prevent TRALI, as females produce more antibodies during pregnancy Sepsis Presentation/Background Occurs due to bacterial contamination of blood products Acute onset of infectious symptoms including fever, chills, rigors[nuemblog.com]
  • The most common symptoms are chills, rigor, fever, dyspnea, light-headedness, urticaria, itching, and flank pain.[merckmanuals.com]
  • Symptoms : Very high fever, rigors, profound hypotension, nausea and/or diarrhoea. Management : Immediately stop the transfusion and notify the hospital blood bank.[rch.org.au]
Congestive Heart Failure
  • Heart Failure (CHF)/Transfusion-Associated Circulatory Overload (TACO) Presentation/Background Risk factors include advanced age, known heart failure/diastolic dysfunction, and renal failure Patients typically develop acute dyspnea, crackles, and hypoxemia[nuemblog.com]
  • Liver and endocrine dysfunction creates significant morbidity and the most serious complication is cardiotoxicity which causes arrhythmias, and congestive heart failure.[rch.org.au]
Urticaria
  • Urticaria with No Other Signs or Symptoms. The appearance of an itchy rash during component transfusion, frequently seen with transfusion of platelets or plasma, is a common occurrence.[enotes.tripod.com]
  • Fever, chills and urticaria are the most common manifestations of transfusion reactions.[transfusion.com.au]
  • While in most cases, generalized urticaria and pruritus are the main symptoms, allergic TR may rarely progress towards life-threatening anaphylaxis.[symptoma.com]
  • Urticaria and erythema sometimes occur in dogs and cats.[medical-dictionary.thefreedictionary.com]
  • Anaphylaxis Presentation/Background The incidence is estimated to be between 1/20,000-150,000 Similar in presentation to anaphylaxis from all other causes and usually occurs early on during the transfusion You know the signs and symptoms: urticaria, pruritus[nuemblog.com]
Pruritus
  • While in most cases, generalized urticaria and pruritus are the main symptoms, allergic TR may rarely progress towards life-threatening anaphylaxis.[symptoma.com]
  • Anaphylaxis Presentation/Background The incidence is estimated to be between 1/20,000-150,000 Similar in presentation to anaphylaxis from all other causes and usually occurs early on during the transfusion You know the signs and symptoms: urticaria, pruritus[nuemblog.com]
  • Allergic reactions include hives, urticaria, pruritus, erythema, bronchospasm, and hypotension. Anaphylactic reactions may occur in IgA-deficient patients.[www3.mdanderson.org]
Dark Urine
  • She complained of severe back pain and dark urine. In addition, she became hypertensive, tachycardic, and jaundiced. The DAT indicated the presence of IgG on the patient's RBCs. Anti-Fy3 was identified in the serum and eluate.[ncbi.nlm.nih.gov]
  • Transfusion reaction symptoms include: back pain dark urine chills fainting or dizziness fever flank pain skin flushing shortness of breath itching In some instances, however, transfusion reactions take place days after the transfusion.[healthline.com]
  • Abdominal distention, jaundice, dark urine, reticulocytosis. If reticulocytosis occurs, it suggests some other associated problem (for example, a deficiency in glucose-6 phosphate dehydrogenase [G6PD]).[pearsonitcertification.com]
  • urine, uncontrolled bleeding due to DIC.[rch.org.au]
  • If AHTR occurs while the patient is under general anesthesia, the only symptom may be hypotension, uncontrollable bleeding from incision sites and mucous membranes caused by an associated DIC, or dark urine that reflects hemoglobinuria.[merckmanuals.com]

Workup

If possible, anamnestic data regarding previous transfusions and possible TR should be provided before starting to transfuse any blood products. In some cases, however, this might not be possible.

Hemolytic reactions may be recognizable by visual inspection of the patient's plasma and urine. Both are probably reddish. As has been mentioned above, if the mistake that lead to mistransfusion can be cleared up, it will be a lot easier to comprehend what is happening between recipient's and donor's blood components. If a simple confusion can be ruled out, Coombs testing may confirm incompatibility and both types of erythrocytes should be retyped [11]. If erythrocytes have indeed been typed wrong, other patients may be at risk of similar incidents. Of note, delayed hemolytic TR are also diagnosed by proving incompatibility, but fresh samples of the recipient's blood, i.e., after the delayed hemolytic TR has taken place, should be used for testing.

Allergic TR do neither cause hemolysis nor hemoglobinuria and this also applies to anaphylactic reactions. If a hemogram is established, eosinophil granulocyte counts are usually not elevated. As its name indicates, a febrile non-hemolytic reaction is not associated with hemolysis or hemoglobinuria either [12]. The clinical presentation is helpful to distinguish all these acute TR.

With regards to TRALI, symptoms should prompt a strong suspicion for this serious TR. Differentiation between TRALI and cardiogenic pulmonary edema may require further diagnostic measures. Serum brain natriuretic peptide levels may be useful to that end and will not be elevated in TRALI patients.

In general, transfusions should be stopped if a TR is suspected. The intravenous access should, however, be maintained to allow for fast responds.

Treatment

The first therapeutic measure is to cease the transfusion. If necessary, subsequent transfusions should consist of blood products of other suitable donors. Ideally, transfusion therapy will not be continued until the cause of the TR is identified.

Fluid resuscitation with crystalloid solutions is indicated after diagnosing an acute hemolytic TR in order to prevent circulatory and renal failure. Forced diuresis may be a second option if fluid therapy is not sufficient to increase urine output. Adequate hydration is a prerequisite for diuresis. Renal failure may require dialysis. If hemolysis triggers considerable hypoxia, additional therapeutic measures such as respiratory support should be considered. Delayed hemolytic TR may be treated similarly, but are usually less severe and do seldom require extensive therapy.

While mild allergic TR are usually self-limiting, but antihistamine application is often recommended. Corticosteroids may provide additional benefit. Moderate cases of allergic TR may progress to anaphylaxis and urgent attention is needed by a patient suffering an anaphylactic reaction: Epinephrine should be administered immediately and may needed to be utilized repeatedly [13]. If intramuscular injections don't yield the desired response, the drug should be applied intravenously. Although bronchospasms may be resolved with bronchodilators, patients should be intubated for safety reasons. Patients may benefit from antihistamines and, in cases of prolonged anaphylaxis, from corticosteroids.

Febrile non-hemolytic TR are treated symptomatically with antipyretics, preferentially with paracetamol.

Respiratory support in any necessary form, i.e., additional oxygen supply or mechanical ventilation, if necessary, is provided to TRALI patients until symptoms subside spontaneously. Hemodynamic parameters should be monitored and circulation may possibly benefit from adequate support.

Several immunosuppressive treatments have been tried for transfusion-associated graft-versus-host disease, but none was found effective. Thus, only symptomatic treatment can be recommended.

High-dose immunoglobulin therapy has been found effective to treat post-transfusion purpura associated thrombocytopenia [14].

Prognosis

Prognosis varies considerably with the specific type of TR and its severity. In this context, most acute hemolytic TR, delayed hemolytic TR, most allergic TR, febrile non-hemolytic TR an post-transfusion purpura are generally associated with an very good prognosis. Many of such reactions are mild and self-limiting. However, if greater amounts of incompatible blood cause acute hemolytic TR or if an allergic TR progresses to anaphylaxis, they may be lethal [9]. TRALI is a potentially life-threatening TR with high mortality [6]. Transfusion-associated graft-versus-host disease is most often fatal [10].

Etiology

Although in general, TR are adverse reactions of the patient's immune system towards transfused blood products, they may be triggered by a variety of incompatibilities. These may affect distinct cell types or other blood components, antigens and antibodies may be provided by donor and recipient or vice versa, and different organs may suffer from TR in the patient's body.

If erythrocytes of an AB0 incompatible donor are transfused, the recipient's IgM antibodies will mediate hemolysis of the transfused red blood cells. This acute hemolytic TR is the result of mistransfusion after unintended errors. If other, non-AB0 antigens on erythrocytes cause TR, particularly if the recipient's immune system only starts antibody production upon receiving the transfusion, hemolytic TR may occur as delayed reactions. Such is the case when Rhesus antigens are transferred to a recipient who is negative for this antigen.

Any potential allergen transfused with blood components may trigger an acute allergic TR, a hypersensitivity reaction.
Other types of acute TR are transfusion-related acute lung injury (TRALI) and acute febrile non-hemolytic TR. The former is presumably mediated by activated neutrophil granulocytes that subsequently trigger severe damage to the endothelium of pulmonary vessels and life-threatening pulmonary edema. With regards to acute febrile non-hemolytic TR, the etiology of this reaction is not yet understood.

Immunodeficient patients are particularly susceptible to transfusion-associated graft-versus-host disease, a type of delayed TR. Here, transfused lymphocytes initiate an immune reaction against the recipient's tissue. Such events are prevented by the recipient's immune system in immunocompetent patients.

Post-transfusion purpura is another type of delayed TR and is associated with thrombocytopenia. Possibly, in this case, cross reactive antibodies produced against transfused antigens mediate lysis of the recipient's thrombocytes.

Epidemiology

The overall incidence of TR has significantly decreased since leukoreduction has been adopted as a standard safety procedure.

Acute hemolytic TR, usually the result of confusion and subsequent transfusion of the "wrong" blood bag, has been repeatedly estimated to happen once or twice per 10,000 transfusions [3]. These accidents may be lethal in approximately 2% of such cases. Delayed hemolytic TR are observed in about 4 per 10,000 transfusions.

Allergic TR range among the most frequent TR and are reported for up to 30 per 10,000 transfusions [4]. Anaphylactic reactions account for about 1% of these cases.

Febrile non-hemolytic TR occurs more frequently than acute hemolytic TR, but less often than allergic TR. Incidence rates have been estimated to up to 19 per 10,000 red blood cell transfusions and up to 15 per 10,000 platelet transfusions. Interestingly, numbers available for transfusions carried out without prior leukoreduction show that incidence rates for febrile non-hemolytic TR were 2-fold and 14-fold increased for erythrocytes and thrombocytes, respectively [5].

The incidence of TRALI has been estimated to be about 10 per 10,000 transfusions. It is the type of TR associated with the highest mortality [6].

Transfusion-associated graft-versus-host disease and post-transfusion purpura are rare phenomena. The former is almost exclusively observed in immunodeficient patients.

Sex distribution
Age distribution

Pathophysiology

Acute hemolytic TR result from an immune reaction between the recipient's IgM antibodies against AB0-antigens of the transfused erythrocytes. Presence of antibodies against other red blood cell antigens of the donor may also trigger an acute hemolytic TR, but such a reaction is usually considerably less severe than that against AB0-antigens. In rare cases, an acute hemolytic TR may result from transfusion of previously damaged erythrocytes and subsequent hemolysis. Here, no immune reaction is taking place and the patient is not presenting symptoms of a typical acute hemolytic TR.

While acute hemolytic TR are typically mediated by IgM, IgE accounts for hypersensitivity and an allergic TR. Causative allergens are usually soluble allergens against which the recipient has already been sensitized. Also, genetic disorders seem to play a role in susceptibility for allergic TR [7].

Acute febrile non-hemolytic TR are little understood. It has been suggested that transfused leukocytic cytokines trigger this type of TR.

With regards to TRALI, there are different hypotheses as to the pathogenesis of this severe reaction. One assumes that antibodies transfused with blood components activate neutrophil granulocytes that subsequently mediate endothelial damage and cause increased vascular permeability. Of note, transfused neutrophil antibodies may trigger different reactions, not all of them leading to pulmonary edema as in TRALI [8]. The alternative hypothesis also concentrates on neutrophil granulocytes, suggests, however, that these immune cells are primed previous to transfusion. Thus, no antibodies need to be transfused. Blood components are merely the straw that breaks the camel's back.

Prevention

In general, the medical history of the patient, focused on previous transfusions and pregnancies, may reveal important information to avoid TR and should be attentively studied.

Severe acute hemolytic TR may be avoided by careful management and assignment of transfusion bags.

Pretreatment of blood and blood products may be required before certain patients, e.g., immunocompromised patients in risk of transfusion-associated graft-versus-host disease, may be transfused.

Summary

Transfusion reaction (TR) is a general term and may refer to any adverse immune response towards previously donated blood products. With regards to symptom onset, acute can be distinguished from delayed TR.

Symptoms of acute TR can manifest as early as transfusion is carried out, but any adverse signs occurring in between 24 hours after transfusion are considered acute reactions. Typically, patients experience fever and chills as well as generalized pruritus and urticaria. In most cases, symptoms are mild and subside spontaneously within a short period of time. Here, no special treatment is required. However, if patients present high fever, dyspnea, hemoglobinuria and reduced consciousness, these are serious indicators of a potentially life-threatening immune reaction [1] [2].

TR may occur days or even weeks after the transfusion. Such delay may, for instance, be caused by the fact that antibodies are not present in the patient's body at the time of transfusion, but have to be produced first.

Any TR should prompt clinical and laboratory investigations as to the nature of the reaction. In some cases, the explanation may be as easy as an error that occurred while someone provided a transfusion bag prepared for another patient. If no such obvious mistake happened, samples of the recipient's and donor's blood should be gathered for further analysis.

Patient Information

Transfusion reaction (TR) is a general term referring to any immune mediated adverse event occurring after receiving blood or blood products. There is a variety of different types of TR and they happen due to distinct causes, they neither manifest in the same way nor require the same treatment:

  • Acute hemolytic TR. Human may have different blood types and the most common classification of blood types is the A, B, AB and 0 system. A patient with blood type A, for instance, possesses A-antigens and B-antibodies. Since they have neither A-antibodies nor B-antigens, nothing happens. If this person does, however, receive a blood type B transfusion, there will suddenly be B-antigens. This triggers an immune reaction and destruction of red blood cells. Acute hemolytic TR usually result from errors upon assignation of transfusion bags, from simple confusion. This confusion may indeed have severe consequences and patients may require fluid therapy, renal and maybe even respiratory support.
  • Delayed hemolytic TR. There are a lot more antigens and antibodies in human blood. Similarly to the reaction described above, other molecules of recipient's and donor's blood may react. In some cases, antibody production only starts upon transfusion and the hemolytic TR will occur days later. Delayed hemolytic TR are often less severe than acute hemolytic TR and only require minimal therapy.
  • Allergic TR. Allergens may cause hay fever and a lot of other diseases. The patient's body may react comparably, albeit much more severely to allergens administered with blood transfusions. While in most cases, generalized urticaria and pruritus are the main symptoms, allergic TR may rarely progress towards life-threatening anaphylaxis. This condition may involve bronchospasm, circulatory failure and shock and requires urgent medical attention.
  • Febrile non-hemolytic TR. The mechanisms behind this mild reaction are not yet completely understood. It manifests mainly with fever and is usually treated symptomatically.
  • Transfusion-associated graft-versus-host disease. This reaction is almost exclusively observed in immunodeficient patients. Their immune system is unable to eliminate lymphocytes transferred with blood transfusions and these lymphocytes start to attack the recipient's tissues. Transfusion-associated graft-versus-host disease is mostly lethal.
  • Post-transfusion purpura. Here, platelet counts drop significantly after receiving blood products. This may be caused by another antigen-antibody reaction. This condition has a very good prognosis and is treated with immunoglobulins.

References

Article

  1. Yeh SP, Chang CW, Chen JC, et al. A well-designed online transfusion reaction reporting system improves the estimation of transfusion reaction incidence and quality of care in transfusion practice. Am J Clin Pathol. 2011; 136(6):842-847.
  2. Fastman BR, Kaplan HS. Errors in transfusion medicine: have we learned our lesson? Mt Sinai J Med. 2011; 78(6):854-864.
  3. Linden JV, Wagner K, Voytovich AE, Sheehan J. Transfusion errors in New York State: an analysis of 10 years' experience. Transfusion. 2000; 40(10):1207-1213.
  4. Keller-Stanislawski B, Lohmann A, Gunay S, Heiden M, Funk MB. The German Haemovigilance System--reports of serious adverse transfusion reactions between 1997 and 2007. Transfus Med. 2009; 19(6):340-349.
  5. Yazer MH, Podlosky L, Clarke G, Nahirniak SM. The effect of prestorage WBC reduction on the rates of febrile nonhemolytic transfusion reactions to platelet concentrates and RBC. Transfusion. 2004; 44(1):10-15.
  6. Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury: a review. Chest. 2004; 126(1):249-258.
  7. Choi G, Soeters MR, Farkas H, et al. Recombinant human C1-inhibitor in the treatment of acute angioedema attacks. Transfusion. 2007; 47(6):1028-1032.
  8. Fadeyi EA, De Los Angeles Muniz M, Wayne AS, Klein HG, Leitman SF, Stroncek DF. The transfusion of neutrophil-specific antibodies causes leukopenia and a broad spectrum of pulmonary reactions. Transfusion. 2007; 47(3):545-550.
  9. Kuriyan M, Carson JL. Blood transfusion risks in the intensive care unit. Crit Care Clin. 2004; 20(2):237-253, ix.
  10. Dwyre DM, Holland PV. Transfusion-associated graft-versus-host disease. Vox Sang. 2008; 95(2):85-93.
  11. Beauregard P, Blajchman MA. Hemolytic and pseudo-hemolytic transfusion reactions: an overview of the hemolytic transfusion reactions and the clinical conditions that mimic them. Transfus Med Rev. 1994; 8(3):184-199.
  12. Ezidiegwu CN, Lauenstein KJ, Rosales LG, Kelly KC, Henry JB. Febrile nonhemolytic transfusion reactions. Management by premedication and cost implications in adult patients. Arch Pathol Lab Med. 2004; 128(9):991-995.
  13. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005; 115(3 Suppl 2):S483-523.
  14. Mueller-Eckhardt C, Kiefel V. High-dose IgG for post-transfusion purpura-revisited. Blut. 1988; 57(4):163-167.

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Last updated: 2018-06-22 02:30