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The role of cytokines in blood transfusion reactions.

Recent advance in the understanding of the mechanism of hemolytic transfusion reactions results from the investigation of cytokine generation in in vitro models of incompatible red blood cell transfusion. Cytokines with pyrogenic and pro-inflammatory activities as well as cytokines with activating properties for granulocytes, monocytes and endothelial cells are produced in both 'intravascular' and 'extravascular' types of hemolytic reactions. It has also been demonstrated that cytokines are generated and accumulated in blood components such as platelet concentrates, during storage. A large part of febrile transfusion reactions results from transfusion of stored platelet concentrates containing high cytokine levels and not from antigen-antibody reactions. Prestorage removal of white blood cells, which generate cytokines during storage, from platelet concentrates reduces strongly the reaction incidence and should be standard practice.

Blood Transfusion↗

Febrile nonhemolytic transfusion reactions. Management by premedication and cost implications in adult patients.

CONTEXT: Febrile nonhemolytic transfusion reactions (FNHTRs) cause unwelcome interruptions during the course of blood product transfusions and necessitate measures to verify the nature of the reaction and to exclude certain dangerous reactions, such as hemolytic and septic phenomena. OBJECTIVE: To examine transfusion medicine data to determine the clinical implications of the routine administration of antipyretic medication to adult patients before transfusion for the prevention of FNHTRs. DESIGN: A retrospective review was conducted of FNHTR data during 5 years (1998-2002), and a determination was made of the cost of a transfusion complicated by an FNHTR. In addition, a comparative cost analysis was performed using our data and published data on the incidence of FNHTRs. The clinical implications of medication with respect to possible drug-induced adverse effects were assessed, as well as the potential interference with diagnosing other forms of transfusion reactions and the mitigation of the clinical effect of an FNHTR. RESULTS: For nearly 120,000 U of transfused blood components, approximately 80% of which were preceded by antipyretic medication during the study period, the overall incidence of FNHTR was found to be 0.09%. Furthermore, there was no evidence of antipyretic-associated complications, nor any evidence that antipyretics prevented the recognition of other more dangerous complications of transfusions. CONCLUSION: Our findings indicate that this practice provides significant advantages to the recipient of a transfusion, but does not appear to yield significant cost benefits for the health care provider.

Acetaminophen↗

Delayed hemolytic transfusion reactions. An often-missed entity.

Delayed hemolytic transfusion reactions in eight persons were manifested solely or primarily by an apparently unexplained posttransfusion decrease in the hematocrit value. Alloantibodies were eventually found in all eight patients, but were sometimes undetectable for as long as 72 hours after the reaction. This did not preclude the occurrence of a new, acute hemolytic reaction. There were three instances of reversible renal failure complicating the reaction. In two patients, some or all of the antibodies became undetectable after four and nine months. In a third, the indirect antiglobulin reactions became considerably weaker after 12 months. Patients previously sensitized to RBC antigens should have available records inspected and a warning device (wristband or wallet card) provided to help prevent reactions caused by an anamnestic antibody rise.

Adolescent↗

Delayed haemolytic transfusion reaction due to anti-M antibody.

A female patient with delayed haemolytic transfusion reaction due to anti-M antibody is described. Diagnosis was based on laboratory evidence of haemolysis and on characteristic serological findings. Anti-M was detected in the recipient's serum 7 d after the last transfusion episode. This alloantibody had not been present in the pretransfusion serum. In addition, the direct antiglobulin test was positive on post-transfusion testing and the implicated antibody was eluted from post-transfused red cells. Delayed haemolytic transfusion reactions have long been recognized as a potential hazard of transfusion therapy, but such cases due to anti-M are extremely rare.

Adenocarcinoma↗

Intravascular hemolytic transfusion reaction without detectable antibodies: A case report and review of literature.

A case of intravascular hemolytic transfusion reaction without detectable antibodies occurring in a 55-year-old male is reported. Specificity for the C antigen in the Rh system was demonstrated by technetium-99m red cell survival studies. A cell-mediated mechanism of hemolysis was suspected and investigated. Previously reported cases are reviewed and discussed. The entity of intravascular hemolytic transfusion reaction associated with minimal symptoms and no detectable antibodies deserves further investigation.

Antigens, Surface↗

Delayed hemolytic transfusion reaction with anti-Jkb erythrocyte antibody after open heart surgery.

A patient suffering from delayed hemolytic transfusion reaction with anti-Jkb erythrocyte antibody after open heart surgery is reported on. On preoperation evaluation, a 42-year-old woman who had never been transfused exhibited a negative erythrocyte autoantibody. After the operation of aortic valve replacement and open mitral commisurotomy, she developed a severe hemolytic anemia with a positive rare anti-Jkb erythrocyte antibody on the 14th postoperative day. Precautions are discussed which need to be taken to distinguish delayed hemolytic transfusion reaction from mechanical hemolysis caused by extracorporeal circulation and prostheses.

Adult↗

A delayed hemolytic transfusion reaction due to anti-Cob.

A delayed hemolytic transfusion reaction precipitated by anti-Cob is described in a multiple transfused primigravida woman with sickle-cell disease. Sixteen days after the prophylactic transfusion of the first of 4 units of red cells, she experienced a fall in hemoglobin concentration accompanied by a newly positive antibody screen and direct antiglobulin test. Anti-Cob was identified both in the patient's serum and in an eluate prepared from her red cells.

Adult↗

Acute hemolytic transfusion reaction secondary to anti-Fy3.

A hemolytic transfusion reaction due to anti-Fy3 is reported in an African American patient with no history of sickle cell disease. This 82-year-old African American woman received two units of RBCs for anemia (Hab 7 g/dL) on admission for a left hip fracture. On hospital Day 7, the patient underwent left hip endoprosthesis surgery; she received two units of RBCs on the second postoperative day due to Hb of 6.1 g/dL. Her urine was dark during surgery and postoperatively. Her posttransfusion plasma was red. Her Hb dropped from 8.4 to 6.4 g/dL over 24 hours after the transfusion. Her total bilirubin rose to 4.0 mg/dL, with and LDH value of 1558 U/L and a haptoglobin of 10.9 mg/dL. Both the antibody detection test and the DAT were positive. An anti-Fy3 was identified in the serum and in the eluate. To the best of our knowledge, this is the first case of acute intravascular hemolysis due to anti-Fy3 in a patient without sickle cell disease.

Acute Disease↗

Rapid evaluation of risk of white particulate matter in blood components by a statewide survey of transfusion reactions.

BACKGROUND: In January 2003, white particulate matter (WPM) was detected in blood components. Because the composition and cause of WPM was not understood at that time, there was uncertainty about whether WPM could endanger patient safety. To investigate possible adverse patient events associated with WPM, transfusion reaction rates were examined. STUDY DESIGN AND METHODS: A questionnaire was distributed to Georgia medical centers. Data collected included the number of components transfused and reported adverse reactions by component type from January 2002 through January 2003, and date, reaction type, and blood supplier for events in January 2003. RESULTS: Of 124 transfusion services contacted, 108 (87%) responded. During the survey period, there were 1213 reported transfusion reactions and 528,412 units transfused, or 2.3 reactions per 1000 units transfused; for RBCs, 2.4 (range, 1.8-3.1); plasma, 1.5 (range, 0.6-3.5); and PLTs, 3.4 (2.1-5.4) per 1000 units. Transfusion reaction rates by component for January 2003 did not differ significantly from the rate for January 2002 or for the calendar year. The 86 reported reactions that occurred in January 2003 were attributed to bacterial contamination (n = 2, 2.3%), other febrile nonhemolytic (n = 49, 57.0%), allergic (n = 14, 16.3%), and "other" reactions (n = 21, 24.4%); the proportions of reaction types did not differ significantly during the month. CONCLUSION: No overall changes in reported adverse reaction rates occurred over the survey period or in the proportion of reaction types during January 2003 when WPM was detected. Statewide surveillance of transfusion reactions could be useful to evaluate potential threats to blood safety.

Blood Specimen Collection↗

Delayed hemolytic transfusion reaction due to anti-Js(a) in an alloimmunized patient with a sickle cell syndrome.

Delayed hemolytic transfusion reactions occur via an anamnestic immune response in patients previously alloimmunized by certain RBC antigens. Conventional pretransfusion antibody screening tests and crossmatches are unable to detect certain antibodies that potentially can cause these reactions because they may be present in low concentrations or have low affinity for their respective antigen or their indicator antigen may be absent from test RBCs. We report the second case of a delayed hemolytic transfusion reaction caused by an undetectable (by routine methods) anti-Js(a) in a patient with a sickle cell syndrome (hemoglobin SC disease) and multiple alloantibodies, in whom retrospective indirect antiglobulin tests enhanced by polyethylene glycol revealed the presence of weakly reactive anti-Js(a).

Female↗

An investigation of nonhemolytic transfusion reactions.

This study was undertaken to document the incidence of immediate, nonhemolytic transfusion reactions and to identify a technique or set of techniques that would best identify the different causes of these reactions. A variety of tests were employed to detect lymphocyte, granulocyte, platelet and anti-IgA antibodies. During this study 26,318 units of blood components were transfused on 5,030 occasions. 191 immediate, nonhemolytic reactions were experienced giving an incidence per unit of 0.73%. Blood specimens from 101 of these patients were investigated along with serum from 57 patients who showed no reaction to transfusion as controls. We show that standard B cell lymphocytotoxicity testing is the technique with which most antibodies can be detected (64% of reactors positive vs. 30% of controls, p less than 0.001). Additional tests did not significantly increase the level of antibody detection.

Antibodies, Anti-Idiotypic↗

Blood and blood transfusion reactions: 1.

Blood transfusion is a well-established mode of treatment for many disorders. This article, the first of two parts, examines the therapeutic indications for blood replacement. The second part will discuss the associated complications and the nursing care required in such situations.

Blood Grouping and Crossmatching↗

Fatal hemolytic transfusion reaction resulting from ABO mistyping of a patient with acquired B antigen detectable only by some monoclonal anti-B reagents.

BACKGROUND: Some monoclonal anti-B reagents are prepared exclusively from an anti-B clone, ES4, that is known to detect acquired B antigens that are not detectable by other anti-B clones or polyclonal anti-B reagents. CASE REPORT: A 92-year-old group A, Rh-negative man with diverticulitis was mistyped as group AB with the use of a monoclonal anti-B. The hospital did not detect anti-B in the patient's serum. After a negative antibody screen, blood was issued through an abbreviated crossmatch (i.e., immediate-spin crossmatch). The patient was given 3 units of group AB blood and 1 unit of group A blood, and no problems were reported. After the transfusion of a ¿fourth unit of AB blood the patient had a severe hemolytic transfusion reaction which resulted in kidney failure and death 10 days later. After the transfusion reaction, the patient's pretransfusion red cells were found to be group A with an acquired B antigen. The monoclonal anti-B used the hospital was formulated from the ES4 clone. A sample of the patient's serum taken before the transfusion was later found to contain a weak anti-B, detectable most obviously by the antiglobulin test, which was not performed at the crossmatch stage. The manufacturers of monoclonal anti-B reagents prepared from ES4 have since modified their reagents (i.e., lowered the pH) so that they now detect only the strongest examples of acquired B antigen. CONCLUSION: A fatal hemolytic transfusion reaction resulted because a monoclonal anti-B that detected acquired B antigen was used to type red cells from an elderly man whose serum had weak anti-B that was not detected by abbreviated compatibility testing.

ABO Blood-Group System↗

Frequency of delayed hemolytic transfusion reactions following antibody screening and immediate-spin crossmatching.

In view of the continuing controversy regarding the use of immediate-spin crossmatch procedures in preparing blood for transfusion to patients in whom unexpected clinically significant antibodies have not been found by antibody screening by the indirect antiglobulin test (IAT), a review of 8 years' experience with such a policy was conducted. In that period, 54,725 units of packed red cells or whole blood were transfused to 10,146 patients. Four clinically overt delayed hemolytic transfusion reactions and 18 clinically silent delayed serologic transfusion reactions were found. In 3 of the 22 patients, the offending antibody(ies) were detectable in the pretransfusion serum by an enzyme IAT, but none was detectable by routine saline IAT against either a three-cell screening panel or the transfused cells. Thus, the incorporation of saline indirect antiglobulin crossmatch would not have prevented the delayed reactions. It can be concluded that the use of a saline indirect antiglobulin crossmatch offers no significant advantage over the current policy of using only immediate-spin crossmatch for those patients whose pretransfusion serum gives negative results in a three-cell screen using a saline IAT.

Aged↗

Mechanisms responsible for delayed and immediate hemolytic transfusion reactions in a patient with anti-E + Jk(b)+ Di(b) and anti-HLA alloantibodies.

Immediate hemolytic transfusion reactions (IHTR) occurred in the course of delayed hemolytic transfusion reactions (DHTR). An 84-year-old man had received a blood transfusion 20 years ago. Progressive anemia developed, because of continuous bleeding from a bladder tumor. He was transfused with concentrated red blood cells (CRC) which were Rh-E antigen negative, because he had anti-E antibodies (day 0). He received CRC on day 3, and underwent resection of bladder tumor on day 6. Although crossmatch-compatible CRCs were prepared for the operation, those were not required and were kept in a refrigerator in the ward. On day 9, when a CRC kept in the ward was transfused, he suddenly had a IHTR. In order to analyze a mechanism of IHTR, the anti-Jk(b) and anti-Di(b) antibodies, anti-HLA antibodies and the concentrations of inflammatory cytokines were measured in serum samples. The anti-Jk(b) and anti-Di(b) antibodies increased prior to IHTR experienced on day 9. The concentrations of IL-6 and IL-1beta increased from day 2, while the concentration of IL-8 increased from day 7. The anti-HLA class I antibody could be detected 2 days before IHTR. Thus, the anti-Jk(b) and anti-Di(b) antibodies induced the production of inflammatory cytokines and symptoms of DHTR and IHTR. The anti-HLA class I antibody could be produced in spite of using the filer for removing leukocytes, and may take part in the induction of IHTR. Further, blood products should be transfused soon after completing a crossmatch test in patients with anti-RBC alloantibodies.

Aged↗

Delayed hemolytic transfusion reactions. Evidence of the need for an improved pretransfusion compatibility test.

Delayed hemolytic transfusion reactions were diagnosed with a frequency of 1 per 4,000 units of whole blood or erythrocytes transfused, which represents an increased frequency of detection for those reported in other studies. The reasons for this increase, as well as the current detection of relatively milder reactions, appear to be related to the careful monitoring of the transfusion process, along with an increased clinical awareness of the problem and more sensitive laboratory detection methods. The increased frequency of detection emphasizes the need for more sensitive pretransfusion crossmatch methods to prevent those delayed hemolytic transfusion reactions that are the result of secondary immune responses.

Adult↗

Hemolytic transfusion reactions due to anti-e+f detectable only by nonstandard serologic techniques.

A patient was transfused with a total of 14 units of red blood cells (RBCs) over 33 days (January 14 to February 15) at two hospitals. Febrile transfusion reactions were noted on three occasions, and hemoglobinuria was seen twice. Alloantibodies were not detected in a sample dated February 14, following a transfusion reaction, and this sample was referred to the North London Blond Transfusion Centre. Further samples were also obtained from before and after all transfusions at both hospitals. The patient's RBCs typed as A, D+, probable Rh phenotype (cDE/cDE). The direct antiglobulin test was negative, and serum samples following the second transfusion were red/brown in color. Serologic investigations were inconclusive on all samples taken until February 13 (after the fourth transfusion). At this time, a weak anti-e reacting by manual polybrene technique and an anti-e+f reacting by two-stage papain technique were detected. The serum also contained potent HLA antibodies. The patient subsequently received leukocyte-depleted group A, cDE/cDE RBCs with out any untoward effect. This case demonstrates the importance of a complete transfusion history and emphasizes that alloantibodies detectable only by nonstandard techniques can be clinically significant.

Journal Article↗

Laboratory tests to exclude IgA deficiency in the investigation of suspected anti-IgA transfusion reactions.

Four methods were compared as to their suitability for excluding IgA deficiency in the investigation of suspected anti-IgA transfusion reactions. The methods were radial immunodiffusion, passive hemagglutination inhibition, sandwich enzyme-linked immunosorbent assay, and membrane enzyme immunoassay. Parallel testing was performed on sera from 40 patients or blood donors previously found to have anti-IgA and low or undetectable levels of IgA. All test methods identified the 40 sera as having abnormally low IgA levels. The membrane enzyme immunoassay required 10 minutes or less for testing, as compared to 3 hours for passive hemagglutination inhibition, 4 hours for sandwich enzyme-linked immunosorbent assay, and 48 hours for radial immunodiffusion. The membrane enzyme immunoassay offers the potential for a rapid, instrument-free screen of IgA levels and therefore may be useful in identifying those patients with suspected anti-IgA anaphylactic transfusion reactions who are not IgA deficient and do not require IgA-deficient blood components for additional transfusions.

Anaphylaxis↗