Transfusion reaction is a general term to describe any adverse reaction of the immune system of a patient after receiving blood products.
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.
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.
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 . 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 . 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.
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 . 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.
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 . TRALI is a potentially life-threatening TR with high mortality . Transfusion-associated graft-versus-host disease is most often fatal .
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.
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 . 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 . 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 .
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 .
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 .
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 . 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.
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.
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  .
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.
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: