Transfusion reactions and other alloimmune hemolytic anemias
What every physician needs to know:
Acute transfusion reactions
These manifest during or soon after the transfusion. The most common types of transfusion reactions are allergic transfusion reactions and febrile non-hemolytic transfusion reactions.
Other types of transfusion reactions include transfusion associated circulatory overload (TACO) and less frequent, but potentially serious reactions that include transfusion related acute lung injury (TRALI), septic reactions, and acute hemolytic reactions. The actions in managing a suspected acute reaction are to halt the transfusion, assess the severity of the suspected reaction and stabilize the patient if necessary, diagnose the suspected reaction, and provide specific treatment for diagnosed transfusion reactions.
Alloimmune hemolytic anemia
This is a consequence of immune mediated hemolysis of transfused erythrocytes or immune mediated hemolysis of endogenous erythrocytes by a foreign antibody. Non-acute immune mediated destruction of transfused red blood cells usually occurs 3 to 10 days following the transfusion and is known as a delayed hemolytic transfusion reaction.
Other forms of alloimmune hemolytic anemia can occur when a foreign antibody circulates in the patient’s immune system, such as occurs when intravenous immunoglobulin (IVIG) or Rh immune globulin (RhIG) are administered. A foreign antibody is also responsible for hemolysis that occurs in hemolytic disease of the fetus and newborn (HDFN).
What features of the presentation will guide me toward possible causes and next treatment steps:
Acute transfusion reactions
If an acute transfusion reaction is suspected, then the most important elements of the patient history include temporal relationship to transfusion(s) and the blood component(s) transfused. Acute transfusion reactions usually occur during or within 6 hours following the transfusion, although acute hemolytic transfusion reactions can occur up to 24 hours following a transfusion.
Septic reactions are most likely associated with platelet transfusions
– Plasma and cryoprecipitate (CRYO) rarely cause septic reactions because they are stored frozen and they rarely cause hemolytic reactions. Presenting signs can be: fever, chills, rigors, or shock.
Acute hemolytic reactions
– Acute hemolytic reactions are most frequently associated with red blood cell (RBC) transfusions
but can be seen with transfused platelets if the blood types of the transfused platelets and patient differ. Presenting signs and symptoms can include: fever, chills, rigors, severe anxiety, flank pain, infusion site pain, and abdominal pain.
Allergic reactions can be associated with any blood component.
– The presence of urticaria or wheezing, with possible breathing difficulties and hypotension would suggest an allergic reaction.
TRALI most often occurs with plasma transfusions but can occur with other blood components that contain plasma
– Symptoms associated with TRALI include: dyspnea, cough, tachycardia, and hypertension.
TACO can occur with any blood component, although CRYO is rarely given in large enough volumes to cause this
– Symptoms include: dyspnea, cough, tachycardia, and hypertension.
A febrile reaction
– This can be associated with any blood component but most frequently occurs with platelet transfusions. Fever, chills, or rigors can be the presenting signs and symptoms.
In the non-acute setting, signs and symptoms of hemolytic anemia may include: fatigue, jaundice, and hemoglobinuria.
In a newborn
– If this occurs in a newborn, then HDFN is more likely if the mother had antibodies to red blood cell antigens detected during prenatal testing. The one exception to this is if RhIG was appropriately administered to the mother during pregnancy. In this setting, antibodies to Rhesus blood group, D antigen (RhD) are expected, and are not likely to cause hemolysis in the neonate, but antibodies to other antigens expressed on the neonatal erythrocytes would still be significant. HDFN can also occur if the mother’s plasma contains anti-ABO antibodies against the newborn’s red blood cells. Such antibodies are expected in certain combinations of maternal and neonatal blood types but in most cases these antibodies do not cause significant hemolysis in the newborn.
Patients who had received IVIG or a high dose of RhIG
– Patients who had received IVIG or a high dose of RhIG administered for immune thrombocytopenia (ITP) in the prior 12 hours to 2 weeks are at increased risk of alloimmune hemolytic anemia from these preparations. Patients who are blood group A or AB are at higher risk of developing alloimmune hemolysis from IVIG than patients who are blood group O or B.
Alternatively, if there are signs and symptoms of new onset hemolysis 3 to 14 days following a RBC transfusion, then a delayed hemolytic transfusion may be occurring
– Such a reaction is much more likely if the patient has a history of a prior transfusion or a prior pregnancy.
What laboratory studies should you order to help make the diagnosis and how should you interpret the results?
Acute transfusion reaction or a delayed hemolytic transfusion reaction
If an acute transfusion reaction or a delayed hemolytic transfusion reaction is suspected, then reporting the suspected reaction to the local blood bank will trigger ordering of the appropriate tests:
Confirm that the correct blood component unit was transfused
– The first step in the work-up is to confirm that the correct blood component unit was transfused to the patient by checking that the tags, labels, and patient indentifiers appropriately match. An error detected at this point would suggest that an acute hemolytic transfusion reaction is much more likely.
Tests to to rapidly detect possible hemolysis
– Tests that are usually performed to rapidly detect possible hemolysis include: testing the urine for hemoglobin and inspecting the serum for visible hemolysis.
The ABO type of the patient’s blood is confirmed to ensure that the patient’s blood type was correctly determined prior to the transfusion
The direct antiglobulin test (DAT/direct Coombs test)
This is performed to determine whether antibodies are coating the patient’s erythrocytes, which would suggest that an immune mechanism may be responsible for hemolysis.
An antibody screen
– Depending on the clinical suspicion of a hemolytic reaction, an antibody screen might be performed on a new patient’s specimen to determine whether anti-RBC antibodies are present, that were not detected prior to the transfusion.
Crossmatch between the patient’s serum and a sample from the transfused RBC unit
– A full crossmatch between the patient’s serum and a sample from the transfused RBC unit can be helpful to determine whether the unit was actually fully compatible with the patient.
Additional tests for a suspected non-hemolytic acute transfusion reaction depend on the presenting signs and symptoms. If the reaction is associated with rigors and or a significant fever, a gram stain and culture can be performed on a sample from the blood component and from the patient’s blood. If the reaction is associated with significant dyspnea, then testing for brain natriuretic peptide (BNP) can help determine whether transfusion circulatory overload is likely.
To determine whether hemolysis occurred in cases of suspected alloimmune hemolysis, a complete blood count (CBC) can help determine whether the hemoglobin/hematocrit (Hb/Hct) are lower than expected. An elevated lactate dehydrogenase (LDH) and bilirubin, and low haptoglobin provide additional evidence for hemolysis. These laboratory tests can help detect hemolysis in general, although these test results are not specific to transfusion related hemolysis.
To test for HDFN, a DAT can be performed on the newborn’s RBCs. A negative DAT makes HDFN extremely unlikely while a positive DAT is consistent with HDFN. The specificity of the antibody can be identified by performing an antibody screen using maternal or neonatal serum. This is important since some antibodies are more likely to cause HDFN than others. Anti-Lewis antibodies, for example, are unlikely to cause HDFN while antibodies to antigens in the Rh system often cause HDFN.
IVIG or RhIg
No test is available to reliably determine whether IVIG or RhIg caused hemolysis.
What conditions can underlie transfusion reactions and other alloimmune hemolytic anemias:
Acute transfusion reactions
Differential diagnosis for acute transfusion reactions are:
Septic reactions are more likely if the patient developed rigors or a high temperature elevation during a platelet transfusion
– These are confirmed by a positive gram stain or culture from the transfused bag.
TACO is more common in patients with cardiac disease
– The diagnosis is supported by a newly elevated BNP in a patient with new onset dyspnea.
TRALI is also associated with dyspnea but TRALI is most likely from plasma or fresh frozen plasma
Acute hemolytic reactions are usually the result of an error causing the patient to receive a RBC unit of the wrong ABO blood type
There is no known underlying patient disorder that predisposes patients to most allergic or febrile reactions
– Although some patients frequently have allergic transfusion reactions.
Delayed hemolytic transfusion reactions
Delayed hemolytic transfusion reactions are most likely in patients who had been previously transfused or pregnant, as those patients may have previously induced an immune response from a prior exposure to a RBC antigen. Subsequent transfusions can induce a strong anamnestic response and associated hemolysis.
IVIG or RhIG
Hemolysis from IVIG or RhIG only occurs in people who have recently received these preparations, and in the case of RhIG, the patient’s own RBCs must be Rh(D)+ and the patient must have received a high dose of RhIG such as may be given for patients with immune thrombocytopenic purpura (ITP). If no other etiology for hemolysis is identified in such a patient, then the infused immunoglobulin preparation is the likely cause.
HDFN is much more likely to occur if the mother is multiparous, or if a primagravid mother experienced a maternal-fetal hemorrhage during her pregnancy, such as might occur if a trauma occurred during the pregnancy.
When do you need to get more aggressive tests:
Upon identification of an acute hemolytic transfusion reaction, additional testing should be performed to identify possible sequelae to the reaction. A CBC, prothrombin time (PT), partial thromboplastin time (PTT), blood urea nitrogen (BUN) and creatinine (Cr) should be measured to determine the Hb/Hct with the ongoing hemolysis, determine whether disseminated intravascular coagulation (DIC) may be occurring, and assess for possible renal damage. If DIC may be developing, then d-dimers should also be tested. These complications are less likely but possible with delayed hemolytic transfusion reactions and the same labs can be drawn if the delayed reaction appears severe.
More aggressive testing is indicated if dyspnea, hypoxia, or other pulmonary symptoms are associated with a suspected acute transfusion reaction:
– This should be measured as it increases with TACO, although it is not very specific and some rise can also be seen with TRALI.
If TRALI is suspected
– The patient’s HLA and neutrophil antigens should be measured and samples of donor plasma should be tested for antibodies to the corresponding antigens. In most cases, samples from female donors are preferentially tested, since female plasma is much more likely to contain antibodies to neutrophil or RBC antigens. Because these TRALI tests require coordinated testing of blood donor and patient samples, all testing is normally arranged by the blood bank.
If an acute transfusion reaction consists of anaphylaxis, immunoglobulin A (IgA) concentrations in the patient’s plasma can be measured, since some patients with IgA deficiency develop severe allergic transfusion reactions when transfused with plasma containing IgA.
If HDFN is suspected, the bilirubin and unconjugated bilirubin should be measured, since increased unconjugated bilirubin in the newborn can occur secondary to hemolysis. Elevations in unconjugated bilirubin in these patients can lead to kernicterus.
If it is unclear whether IVIG or RhIG is responsible for hemolysis, some tests may help support or refute the diagnosis. If either product is causing the hemolysis, the DAT should be positive. Additional testing to determine the specificity of the antibody coating the RBCs is not usually needed to make the diagnosis, but if it is performed, the antibody should be directed against the Rh(D) antigen if RhIG is implicated, and usually against antigens of the ABO group if IVIG is implicated.
What imaging studies (if any) will be helpful?
If TRALI is suspected, a chest radiograph should be performed. Bilateral infiltrates throughout the lung fields is seen in TRALI.
What therapies should you initiate immediately and under what circumstances – even if root cause is unidentified?
For suspected acute transfusion reactions:
Supportive fluids can be given to maintain blood pressure and maintain adequate renal perfusion, unless TACO is suspected
Antipyretics can be given to treat fevers and meperidine can be used to treat rigors
Antihistamines can be used to treat mild-moderate allergic reactions, corticosteroids can be used to treat severe allergic reactions, and epinephrine can be administered for anaphylactic reactions
If hypoxia or dyspnea is present, then oxygen should be administered
If TACO is suspected, the patient should sit upright, be given diuretics, and intravenous fluid administration should be minimized
If TRALI is suspected, the patient should be given oxygen as needed
If hypotension develops, as can happen with TRALI, acute hemolytic, and septic reactions, pressors should be given
If a substantial fever and possible rigors or hypotension is associated with the reaction, broad spectrum antimicrobials can be administered
– Until there is evidence that the unit was not contaminated with bacteria.
In general, RBCs should not be transfused until the blood bank work-up has ruled out a hemolytic reaction, or determined the etiology of a hemolytic reaction. If a RBC transfusion is emergently needed, emergency release O Rh(D)- (that lack the A, B and Rh[D] antigens) units may be the safest to transfuse, depending on the blood bank policy and the likelihood of a hemolytic reaction based on the patient’s history, signs, symptoms, and available laboratory results.
Suspected delayed hemolytic transfusion reactions
Suspected delayed hemolytic transfusion reactions rarely need immediate therapy, but the same immediate therapies for acute hemolytic transfusion reactions may be indicated for delayed hemolytic transfusion reactions in rare cases associated with severe hemolysis.
If HDFN is suspected, transfusions, and/or exchange transfusions can be considered. While symptomatic anemia in a newborn should be corrected as soon as possible, it is important to transfuse with RBCs that won’t be hemolyzed. If the blood bank laboratory tests on the mother and baby are still being performed, transfusion of O Rh(D)- RBCs may be indicated for symptomatic anemia. If this is needed, the transfused O Rh(D)- RBCs may be hemolyzed if the pathogenic antibody is directed against another antigen, and a subsequent exchange transfusion performed will likely be needed to remove bilirubin and the cells at risk for hemolysis with transfused RBCs and plasma.
If significant symptomatic anemia secondary to IVIG or RhIG is suspected, RBCs can be transfused immediately. If RhIG is implicated, the transfused RBCs should be Rh(D)-. If IVIG is implicated, transfusion with blood group O RBCs is advisable, since IVIG can contain significant titers of anti-A.
What other therapies are helpful for reducing complications?
The following approaches are used to prevent acute transfusion reactions:
Important strategies to prevent acute hemolytic transfusion reactions
– The most important preventive strategies to prevent acute hemolytic transfusion reactions include adherence to policies designed to ensure accurate patient identification, specimen labeling, and transfusion of correct blood components.
Most American blood banks minimize transfusion of plasma rich blood components to reduce the risk of TRALI.
– Reporting suspected TRALI reactions to the blood bank also allows the blood bank to prevent subsequent transfusions from donors whose blood has caused TRALI.
Preventing allergic or febrile non-hemolytic transfusion reactions in patients who have no history of such reactions
– No strategies are indicated to prevent allergic or febrile non-hemolytic transfusion reactions in patients who have no history of such reactions, but some approaches help reduce those who have had repeated or severe reactions.
1) To reduce the incidence of repeated allergic transfusion reactions, premedication with an antihistamine such as diphenhydramine is indicated. If the patient has had anaphylactic reactions, transfusion with washed cellular blood components (RBCs and platelets) and/or premedication with a corticosteroid may help prevent future reactions. If anaphylactic reactions are due to IgA deficiency, blood components from IgA deficient donors may be available with advance planning.
2) To reduce the risk of repeated febrile transfusion reactions, one can transfuse leukoreduced blood components and premedicate the patient with an antipyretic such as acetaminophen for subsequent transfusions.
Treatment of acute transfusion reactions depends on the type of reaction:
The goal of treatment of acute hemolytic transfusion reactions is to minimize complications from the reactions
– The patient should be monitored since shock can develop and the patient may need pressor support. To help maintain pressure, intravenous normal saline should be administered to maintain urine output of at least 1 mL/kg/Hr. Low dose dompamine hydrochloric acid (1 to 5ug/kg/minute) may help maintain renal blood flow. Furosemide (40 to 80mg. intravenously) also promotes renal blood flow. Plasma, platelets, and or CRYO can be used to treat DIC, if it develops. Additionally, heparin may be tried, though the efficacy has not been proven in this setting. While activated protein C has been shown to be of some benefit to septic patients with DIC, such a benefit has not been demonstrated for DIC secondary to other causes such as a hemolytic transfusion reaction.
TACO can be treated by placing the patient in an upright sitting position, giving oxygen, diuretics, and reducing intravenous fluid administration
– If the patient continues to be symptomatic, phlebotomy may be indicated to rapidly reduce intravascular volume.
TRALI is treated by with oxygen and pressors, as needed. Intubation may be required in severe cases
Febrile reactions are treated with an antipyretic such as acetaminophen. Rigors can be treated with meperidine
Mild allergic reactions are treated with an antihistamine such as diphenhydramine
– Severe and anaphylactic reactions are treated with epinephrine and corticosteroids.
Delayed hemolytic transfusion reactions
Blood banks minimize the risk of delayed hemolytic transfusion reactions by performing antibody screens, identifying antibodies, and avoiding transfusion of RBCs expressing the corresponding antigens. If some of these steps are skipped for an emergency transfusion, the risk of a delayed hemolytic transfusion increases. Because the concentrations of some antibodies diminish over time, blood banks may not detect antibodies in a patient, despite the fact that corresponding memory B cells are present. These patients are at increased risk of delayed hemolytic transfusion reactions.
To reduce this risk, clinicians should obtain a history of transfusions, tranfusion reactions, and antibodies and report positive responses to the blood bank, which can use that information in identifying antibodies and determining the safest RBC units to transfuse. A delayed hemolytic transfusion reaction usually requires little to no treatment, but if severe, the treatment recommendations for acute hemolytic transfusion reactions apply.
Most cases of HDFN can be prevented by administration of RhIG to pregnant women who type as Rh(D)- at 28 weeks gestation, after trauma or invasive procedures during pregnancy, and post-partum if the baby erythrocytes are Rh(D)+. HDFN can be treated by intrauterine transfusion of the fetus and simple, or more frequently exchange transfusions of the neonate.
Hemolysis from IVIG or high dose RhIG
There is no effective approach to prevent hemolysis from IVIG or high dose RhIG administered for ITP, other than choosing alternate therapies. RhIG can cause severe, life threatening hemolysis and transfusion with Rh(D)- RBCs is often required following high dose RhIG given to Rh(D)+ patients for ITP. Transfusion with group O RBCs are indicated if transfusions are needed for IVIG induced hemolysis. Because complications associated with acute hemolytic transfusion reactions, such as DIC and renal damage can occur with RhIG or IVIG induced hemolysis, the treatment recommendations for acute hemolytic transfusion reactions apply.
What should you tell the patient and the family about prognosis?
Acute hemolytic transfusion reactions
Acute hemolytic transfusion reactions from transfusion of ABO incompatible RBCs with mortality rates of 25% for transfusion of 500 to 1,000mL of incompatible RBCs to 44% for transfusion of greater than 1,000mL of RBCs. Hemolytic transfusion reactions from antibodies to other antigens are rarely fatal, but the mortality risk depends on the amount of transfused RBCs, subject to immune mediated hemolysis and the underlying health of the patient. Most patients who survive will fully recover without significant sequelae, although some patients suffer long-term consequences, such as renal damage or other damage secondary to shock or DIC.
Delayed hemolytic transfusion reactions
Delayed hemolytic transfusion reactions are rarely fatal and full recovery is generally expected.
Septic transfusion reactions
Septic transfusion reactions can be fatal, although most cases are not. The seriousness is based on the bacteria species involved, the amount of bacteria transfused, and the patient’s underlying medical condition.
Mild allergic and febrile transfusion reactions
Mild allergic and febrile transfusion reactions are almost never fatal and full recovery is expected.
Anaphylactic reactions should not be fatal when appropriate therapy is promptly initiated.
Administration of RhIG or IVIG
Severe hemolysis can occur following administration of RhIG or IVIG. In rare cases, hemolysis reported with RhIG has been fatal. Hemolysis can also cause renal damage. Treatment is aimed at maintaining adequate Hb/Hct and protecting the kidneys. Renal damage is almost always reversible, even in patients that temporarily require dialysis.
Therapy to treat HDFN is aimed at preventing damage from hemolysis such as kernicterus, renal damage, and maintaining an adequate Hb/Hct. Most cases of live births are not fatal and a full recovery will be expected, although severe (even fatal) cases occur. Severe cases have more rapid hemolysis and more severe anemia.
“What if” scenarios.
Hemolysis associated with IVIG, RhIG, HDFN, and delayed hemolytic transfusion reactions can proceed for days to weeks and ongoing monitoring of the patient is essential, until it is clear that hemolysis has resolved. A patient who has received an exchange transfusion for HDFN should have a CBC performed every 1 to 2 weeks until the Hb has clearly stabilized.
TRALI is not due to volume overload and does not respond to diuretics. Other than oxygen support, little has been demonstrated to help TRALI.
Acute hemolytic transfusion reactions
Acute hemolytic transfusion reactions occur when the patient’s plasma has preformed antibodies directed against antigens on transfused RBCs, or rarely when preformed antibodies in donor plasma contained in a platelet component react against the patient’s RBCs. Preformed immunoglobulin M or G (IgM or IgG) antibodies bind to RBCs and fix complement, which can lead to assembly of a membrane attack complex on the RBCs and intravascular hemolysis.
Activation of the complement cascade leads to release of anaphylatoxins C3a and C5a, which promote release of serotonin and histamine from mast cells that can promote bronchial and intestinal smooth muscle contraction. Other cell types release additional cytokines, leukotrienes, free radicals, and nitric oxide in response to C3a and C5a. Some extravascular hemolysis can also occur through the same mechanisms as describe below.
Delayed hemolytic transfusion reactions, IVIG, RhIG, and HDFN
Hemolysis associated with delayed hemolytic transfusion reactions, IVIG, RhIG, and HDFN, is mostly due to coating of RBCs with immunoglobulin and sometimes C3b. The coated RBCs undergo extravascular hemolysis being cleared by the reticulendothelial system. Though anaphylatoxins can be released during this process, it is usually less prominent than with acute intravascular hemolysis. Some intravascular hemolysis can also occur with these delayed hemolytic transfusion reactions: IVIG, RhIG, and HDFN.
Allergic transfusion reactions
Allergic transfusion reactions are due to preformed antibodies to plasma proteins in the transfused blood component.
Febrile transfusion reactions
Febrile transfusion reactions are due to cytokines that are released from leukocytes and platelets during storage or that are released upon transfusion. Preformed antibodies in patients that react with transfused leukocytes or platelets can cause release of cytokines and a febrile reaction. These antibodies may be directed against foreign HLA antigens or possibly other leukocyte or platelet antigens.
TRALI is thought to be due to transfusion of antibodies to HLA or neutrophil antigens, and possibly transfusion of biologic response modifiers that activate pulmonary endothelial cells and prime neutrophils, leading to pulmonary edema.
TACO is due to the sudden infusion of fluid with high oncotic pressure that occurs during a transfusion, in a patient who cannot respond to the sudden change.
What other clinical manifestations may help me to diagnose transfusion reactions and other alloimmune hemolytic anemias?
What other clinical manifestations may help me to diagnose transfusion reactions?
To reduce the risk of transfusion reactions, ask about prior transfusion history, transfusion reactions, and the facility where the reactions occurred. Also, ask if the patient was ever told they developed an antibody from a transfusion or from past pregnancies. All of this information should be reported to the blood bank.
Any unexpected change in signs or symptoms during or shortly after a transfusion should be considered a possible transfusion reaction. The situation should be evaluated following local protocol, because signs and symptoms of a serious hemolytic reaction can vary greatly and may include infusion site pain, flank pain, nausea, vomiting, hypotension, hypertension, or sudden anxiety. Oozing or uncontrolled bleeding can also suggest DIC and may indicate that a transfusion reaction has occurred.
What other additional laboratory studies may be ordered?
If an acute allergic reaction is severe and IgA deficience is suspected, IgA plasma concentrations and antibodies to IgA can be measured.
Antibodies of unclear specificity are sometimes identified in delayed hemolytic transfusion reactions. In these cases, it sometimes helps to perform DNA single nucleotide polymorphism testing, and sometimes gene sequencing, to determine if unusual RBC antigenic variants are present. These are especially common in the Rh genes in people of African descent.
What’s the evidence?
Daw, Z, Padmore, R, Neurath, D. “Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis”. Transfusion. vol. 48. 2008. pp. 1598-1601 . [Case series of 16 patients who received high doses of IVIG and developed hemolysis. Risk factors, a proposed mechanism, and a protocol for early detection are presented.]
Eder, AF. “Update on HDFN: new information on long-standing controversies”. Immunohematology. vol. 22. 2006. pp. 188-195. [Review and update on the pathophysiology, prevention, and treatment of HDFN.]
Gaines, AR, Lee-Stroka, H, Byrne, K. “Investigation of whether the acute hemolysis associated with Rh(o)(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model”. Transfusion. vol. 49. 2009. pp. 1050-1058. [Study finding that the mechanism of RhIG induced hemolysis differs from hemolysis that occurs in acute hemolytic transfusion reactions.]
Heddle, NM, Klama, LN, Griffith, L, Roberts, R, Shukla, G, Kelton, JG. “A prospective study to identify the risk factors associated with acute reactions to platelet and red cell transfusions”. Transfusion. vol. 33. 1993. pp. 794-797. [Study finding that older blood components and transfusion of platelets are risk factors for febrile transfusion reactions and that antipyretics help reduce the incidence of fever but not other symptoms associated with such reactions.]
Janatpour, KA, Kalmin, ND, Jensen, HM, Holland, PV. “Clinical outcomes of ABO-incompatible RBC transfusions”. Am J Clin Pathol. vol. 129. 2008. pp. 276-281 . [Retrospective study finding that the volume of incompatible blood transfused is proportional to the severity of symptoms and finding that hypotension, hemoglobinuria and/or hemoglobinemia were the most frequent signs and symptoms.]
Kleinman, S, Caulfield, T, Chan, P. “Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel”. Transfusion. vol. 44. 2004. pp. 1774-1789. [Consensus panel statement defining and reviewing signs, symptoms, and pathophysiology of TRALI.]
Li, G, Daniels, CE, Kojicic, M. “The accuracy of natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic) in the differentiation between transfusion-related acute lung injury and transfusion-related circulatory overload in the critically ill”. Transfusion. vol. 49. 2009. pp. 13-20 . [Study finding that BNP values tend to be higher in transfusion related circulatory overload than in TRALI cases but that the diagnostic value of the BNP test is only moderate because of overlapping BNP values between the two diagnostic groups.]
Muylle, L, Joos, M, Wouters, E, De, Bock, Peetermans, ME. “Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: relationship between TNF alpha and IL-6 levels and febrile transfusion reactions”. Transfusion. vol. 33. 1993. pp. 195-199. [Study finding that extra-cellular TNF alpha and IL-6 concentrations during storage of whole blood derived platelets and elevated levels of these cytokines in the transfused platelet component is a risk factor for a febrile transfusion reaction.]
Paglino, JC, Pomper, GJ, Fisch, GS, Champion, MH, Snyder, EL. “Reduction of febrile but not allergic reactions to RBCs and platelets after conversion to universal prestorage leukoreduction”. Transfusion. vol. 44. 2004. pp. 16-24. [Large multicenter study finding that use of prestorage leukoreduction decreased febrile reactions by 93%.]
Popovsky, MA, Audet, AM, Andrzejewski, C. “Transfusion-associated circulatory overload in orthopedic surgery patients: a multi-institutional study”. Immunohematology. vol. 12. 1996. pp. 87-89. [Study identifying risk factors and response to therapy for TACO.]
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- Transfusion reactions and other alloimmune hemolytic anemias
- What every physician needs to know:
- What features of the presentation will guide me toward possible causes and next treatment steps:
- What laboratory studies should you order to help make the diagnosis and how should you interpret the results?
- What conditions can underlie transfusion reactions and other alloimmune hemolytic anemias:
- When do you need to get more aggressive tests:
- What imaging studies (if any) will be helpful?
- What therapies should you initiate immediately and under what circumstances – even if root cause is unidentified?
- What other therapies are helpful for reducing complications?
- What should you tell the patient and the family about prognosis?
- “What if” scenarios.
- What other clinical manifestations may help me to diagnose transfusion reactions and other alloimmune hemolytic anemias?
- What other additional laboratory studies may be ordered?