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Hemagglutination assays for the diagnosis and prevention of IgA anaphylactic transfusion reactions.

Passive hemagglutination assays (PHA) may be used to detect IgA antibodies to confirm clinical diagnoses of suspected IgA anaphylactic transfusion reactions. Passive hemagglutination inhibition assays (PHIA) may be used to identify IgA-deficient blood donors whose plasma-containing components are transfused to prevent anaphylactic transfusion reactions in prospective recipients at risk because of the presence of IgA antibodies. Using a standard PHA, we detected class-specific anti-IgA in 76.3% of 80 IgA-deficient patients with a history of an anaphylactic transfusion reaction, and in 21.7% of 97 asymptomatic IgA-deficient blood donors or their IgA-deficient family members. Using PHIA, we confirmed IgA deficiency (< 0.05 mg/dL) for the donors of 525 plasma-containing blood components that were transfused without acute clinical reactions to 48 IgA-deficient recipients with anti-IgA and/or a history of an anaphylactic transfusion reaction. The frequency of IgA-deficiency with class-specific anti-IgA among 32,376 random blood donors was 0.08% (1/1,200). The combined use of PHA for detecting anti-IgA and PHIA for measuring IgA concentration provides an effective and safe strategy for the diagnosis and prevention of IgA anaphylactic transfusion reactions. However, PHA for anti-IgA lacks specificity for identifying persons who are truly at risk for significant anaphylactic transfusion reactions. The consequence is an overdiagnosis of IgA anaphylactic transfusion reactions and an overestimation of the number of persons at risk for IgA anaphylactic transfusion reactions because of the detection of an IgA antibody in their serum.

Anaphylaxis↗

[Clinical evaluation of various preventive methods for non-hemolytic transfusion reactions].

A study has been carried out on the incidence of non-hemolytic transfusion reaction on a group of patients suffering from thalassemia. Of this group, the rate of reactions per patient, based on the relationship between the number of patients with non-hemolytic transfusion reactions and the total number had risen to 31.8%. 83.7% of the patients with non-hemolytic transfusion reactions did not give a positive reaction to lymphocytotoxicity. 654 patients having, or not having shown a non-hemolytic transfusion reaction received washed red cell concentrates prepared extemporaneously. This process allowed the rate of reaction per patient to drop to 3.9%. The transfusion of deleucocytated red cell concentrates by filtration, carried out on a group of 188 patients, made the rate of reaction per patient drop to 2.8%. As regards to rate reaction per patient, there is no significant difference statistically between these two groups, however, it must be pointed out that the administration of filtered red cell concentrates, by deleucocytation, notably improves the incidence of a feverish reaction, while the administration of washed red cell concentrates has an important impact on allergic reactions. Interestingly, in solution, the washed red cell concentrates have the added advantage of having only very small quantities of free iron or vasoactive proteic derivatives. The new four bag system, now allows us to collect, separate and wash in a closed circuit. Compared to the traditional method this system has the advantage of assuring greater efficiency and security. In conclusion, for the first time, the administration of washed red cell concentrates on patients who receive regular transfusions, may represent a good procedure, combined or not with deleucocytation by filtration, as to prevent the occurrence of non-hemolytic reactions.

Case-Control Studies↗

[Transfusion reactions in patients: haemovigilance reports to the Dutch National Haemovigilance Office in 2003].

OBJECTIVE: National registration and analysis of unexpected side effects and incidents associated with blood transfusion (together termed 'transfusion reactions') in 2003 in order to arrive at recommendations to improve safety in the transfusion chain. DESIGN: Observational METHOD: A uniform national reporting form with definitions and a reporting manual were sent to all Dutch hospitals in the spring of 2003 with the request to report transfusion reactions retroactively to January 2003 to the Dutch National Haemovigilance Office 'Transfusion reactions in patients' (TRIP). TRIP is an independent organisation managed by representatives of professional societies that are involved in blood transfusion. Each hospital was given a reporting code. The reports were in principle voluntary and anonymous with regard to both the patient and the attending physician. Transfusion reactions were assessed for severity as well as for the level of probability with which they could be ascribed to the transfusion. RESULTS: Reports were received from 82 (80%) of the hospitals; 9 hospitals informed the TRIP explicitly that there had been no transfusion reactions in 2003. A total of 267 reports were received. Of these, 803 (63%) were graded for severity and of these 803, 52 (6%) were grade 2 ('moderate to severe morbidity') or worse. In the categories involving possible infectious complications, there were 2 reports of bacterial contamination that were judged, on review, to be due 'with certainty' to the transfusion. 34 reports concerned transfusion of the wrong blood product, resulting in a total of 9 transfusion reactions (4 of grade 2). The total number of reports concerning 2003 was 1.6/1000 blood products. CONCLUSION: The participation by the hospitals was high in the first year of national reporting, 2003. Most of the reports were of non-serious reactions known to be possible side effects of blood transfusion; 52 reports were rated as grade 2 or worse.

Blood Banks↗

[Transfusion reactions after SAG-M blood].

The most common type of transfusion reaction is the febrile reaction, which is often caused by microaggregates in the blood transfused. Reducing the content of microaggregates lowers the rate of transfusion reactions. SAG-M blood is depleted of microaggregates. After changing from whole blood to SAG-M blood, the frequency of transfusion reactions fell from 0,83% to 0,24%.

Blood Group Incompatibility↗

Delayed hemolytic transfusion reactions in sickle cell anemia.

Delayed hemolytic transfusion reaction (DHTR) developed in three patients with sickle cell anemia seen over an 18-month period at Cook Country Hospital. The DHTR was associated with severe pain crisis, with spherocytic hemolytic anemia, a positive direct antiglobulin test result, previously undetected erythrocyte alloantibodies, and disappearance of Hb A on cellulose acetate electrophoresis. Delayed hemolytic transfusion reactions may be more common than is generally recognized and should be considered when a patient has a sickle cell pain crisis shortly after receiving a transfusion.

Adult↗

Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs.

BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTR) is a relatively common complication associated with allogeneic transfusion. Because WBCs have been implicated in the mechanism of FNHTRs, it has been proposed that the transfusion of leukoreduced RBCs should be associated with a decreased incidence of FNHTRs. These reactions are generally not life threatening, but they are expensive in their management, evaluation, and associated blood-product wastage. Over the past several years, the proportion of leukoreduced RBCs has increased at Johns Hopkins Hospital in an effort to move toward complete leuko-reduction. A retrospective analysis is reported here of FNHTRs in RBC recipients as the inventory increased in percentage of leukoreduced RBC units. STUDY DESIGN AND METHODS: Between July 1994 and December 2001, all transfusion reactions (TRs) associated with the transfusion of allogeneic RBCs were retrospectively analyzed. Both computerized data and individual TR reports were reviewed. Patients who had both allergic and febrile features were included as part of both categories. TRs were reported as a percentage of total units transfused. Two time periods were selected for direct comparison. July to December 1994 represents the time period before the initiation of an increase in leuko-reduction. July to December 2001 represents a time period when almost complete leukoreduction (99.5%) had been achieved. The TR data were compared between these two time periods, comparing a time before leuko-reduction to a time period after leukoreduction had been achieved. The trends in TRs over the entire 7.5-year period of July 1994 to December 2001 were also assessed. RESULTS: In the initial period before the initiative to move toward leukoreduction, 96 percent of our RBC inventory was non-leukoreduced. In the study period after leukoreduction, 99.5 percent of our RBC inventory was leukoreduced. When comparing these two time periods, the incidence of FNHTRs decreased from 0.37 percent to 0.19 percent (p = 0.0008). The trend over the entire 7.5-year study period confirms the decrease in FNHTRs as the percentage of leukoreduced RBCs increased. The incidence of allergic TRs has remained unchanged over this time period. CONCLUSIONS: As our institution has increased its inventory of leukoreduced RBCs to approximately 100 percent, selective leukoreduced protocols have been discontinued. The incidence of FNHTRs has decreased significantly and the rate of allergic reactions has essentially remained unchanged. Leukoreduction is effective in decreasing FNHTRs associated with the transfusion of allogeneic RBCs.

Erythrocyte Transfusion↗

Acetaminophen and diphenhydramine premedication for allergic and febrile nonhemolytic transfusion reactions: good prophylaxis or bad practice?

Febrile nonhemolytic and allergic reactions are the most common transfusion reactions, but usually do not cause significant morbidity. In an attempt to prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine premedication before more than 50% of blood component transfusions. Acetaminophen and diphenhydramine are effective therapies for fever and allergy, respectively, so their use in transfusion has some biologic rationale. However, these medications also have potential toxicity, particularly in ill patients, and in the studies performed to date, they have failed to prevent transfusion reactions. Whether the benefits of routine prophylaxis with acetaminophen and diphenhydramine outweigh their risks and cost requires reexamination, particularly in light of the low reaction rates reported at many institutions even when premedication is not prescribed.

Acetaminophen↗

The role of cytokines in hemolytic transfusion reactions.

Experimental evidence is accumulating to support a central role for cytokines in the pathophysiology of hemolytic transfusion reactions. The production of tumor necrosis factor, interleukin-8, and monocyte chemoattractant protein occurs in whole blood in response to ABO incompatible red cells, a model of acute hemolytic transfusion reactions. Peripheral blood mononuclear cells may produce interleukin-1 beta, tumor necrosis factor, interleukin-8, monocyte chemoattractant protein, and interleukin-1 receptor antagonist in response to IgG-coated red cells, a model of delayed hemolytic transfusion reactions. Cultured umbilical vein endothelial cells respond to conditioned plasma from ABO-incompatibility reactions by expressing the procoagulant tissue factor and the leukocyte adhesion molecules ELAM-1 and ICAM-1. These in vitro endothelial cell responses can be inhibited by neutralizing antibodies to tumor necrosis factor, suggesting that TNF may have a central role in intravascular coagulation and end-organ injury that may occur in acute hemolytic transfusion reactions.

Cytokines↗

Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions.

Two anhaptoglobinemic patients showing anaphylactic transfusion reactions by antihaptoglobin antibody were found. Southern blot analysis indicated that 2 patients were homozygous for the deleted allele of the haptoglobin gene (Hp(del)) as reported previously. We have identified the junction region of the deletion from genomic DNA of 1 patient using cassette-mediated polymerase chain reaction (PCR). Then, the deleted region from the 5' breakpoint to the promoter region of the Hp was amplified from genomic DNA of a control individual using PCR. DNA sequence analysis of these regions indicated that the 5' breakpoint of the Hp(del) allele was located 5. 2 kilobase (kb) upstream of exon 1 of the Hp and the 3' breakpoint was positioned between 52 and 53 base pair (bp) upstream of exon 5 of the haptoglobin-related gene. There was no significant homology between the DNA sequences flanking the 5' and 3' breakpoints, except for a 2-bp (TG) identity. To examine the gene frequency, we have developed a simple PCR method to detect the gene deletion. We found 8, 16, and 17 Hp(del) alleles in 157 Koreans, 523 Japanese, and in 284 Chinese, respectively, but did not find the Hp(del) in 101 Africans or in 100 European-Africans. The incidence of individuals homozygous for the Hp(del) allele was therefore expected to be 1/4000 in Japanese, 1/1500 in Koreans, and 1/1000 in Chinese. This incidence is higher than that of IgA deficiency in Japanese. More attention should be paid on haptoglobin deficiency and antihaptoglobin antibody as the cause of transfusion-related anaphylactic reactions in Asian populations. (Blood. 2000;95:1138-1143)

5' Untranslated Regions↗

Case reports: delayed hemolytic transfusion reaction in sickle cell disease.

This article reports the details of delayed hemolytic transfusion reactions in four patients with sickle cell disease. These cases demonstrate the characteristics of the reactions, the significant risks involved, and the principles useful in diagnosis and treatment. Patients with sickle cell disease are at particular risk for delayed hemolytic transfusion reactions because they may be transfused at intervals over many years; they frequently form alloantibodies because of antigenic differences from the donor population; and they may receive emergency care in different hospitals where transfusion records are not available. In addition, exchange transfusions, which are often used for patients with sickle cell disease and which were given in three of these cases, raise the risks through increased exposure to foreign erythrocyte antigens and through an increased volume of erythrocytes susceptible to hemolysis. It was concluded that the hazards of these transfusion reactions justify preventive measures, such as extended erythrocyte phenotyping of patients with sickle cell disease and extended phenotypic matching of transfused cells.

Adult↗

[Delayed hemolytic transfusion reaction caused by an anti-U].

Delayed hemolytic transfusion reactions due to anti-U are rare, only two (2) cases having been reported in the literature. We now report a third case: a multiparous black woman without any transfusion history was admitted to hospital for severe microlytic anemia (31 g/l). The patient was group AB negative, the direct antiglobulin test was negative and an anti P1 cold allo-antibody was present in her serum. Five A, Rh negative, P2 packed red cells were cross-marched with the sample obtained at admission on January 8, 1988. She was transfused on January 8, 9, 10, 11 and 12. On the 12th of January her hemoglobin level reached 125 g/l. On January 13, the patient presented clinical signs of hemolysis and her hemoglobin fell to 60 g/l within 24 hours. On January 15, the direct antiglobulin test was positive and an antibody found in her serum was reactive with all the red cells of the commercial panel. The sample was referred to our red cell serology reference laboratory. The phenotype of the pre-transfusion sample was found to be Fy(a-b-) M, N, S-s-U-. An anti-U was detected in the eluate and the serum. The patient was transfused with two (2) units of O-P2, U-red cells obtained from the American Red Cross, Syracuse, and her hemoglobin reached 90 g/l within 48 hours. This is the third reported case of a delayed hemolytic transfusion reaction due to anti-U. This case illustrates the need to perform cross-matches with samples obtained within 48 hours of the scheduled transfusion for patients who have been transfused with blood in the preceding 3 months. Also, this case emphasises the need to recruit U negative blood donors for the Canadian rare donor file.

Anemia↗

The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance.

Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty-four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti-IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common.

Adolescent↗

Canine transfusion reactions and their management.

There is a wide range of mechanisms by which transfusion reactions may occur. These reactions typically are categorized as immune- or nonimmune-mediated and also as to whether they are acute or delayed in nature. The type and severity of clinical signs vary according to the specific reaction present. Many reactions can be prevented with the use of standard and appropriate transfusion medicine procedures. These methods include careful collection and storage of blood products, adequate screening and blood typing of donor dogs, crossmatching donor and recipient blood, use of component therapy, correct administration of blood products, and the use of pretransfusion prophylaxis when appropriate. Because many reactions are dose dependent, careful monitoring of transfusions cannot be overemphasized. Rapid recognition of a transfusion reaction and immediate discontinuation of the transfusion, along with appropriate supportive therapy, is essential for the successful treatment of transfusion reactions. A summary of transfusion reactions including clinical signs, diagnosis, and basic treatment protocols is given in Table 4. When used appropriately, transfusion of blood products can be a highly beneficial, low-risk form of therapy.

Acute Kidney Injury↗

The serological investigation of red cell incompatible transfusion reactions.

The hospital blood bank plays a key role in the diagnosis of acute transfusion reactions involving red cell incompatibility. This paper discusses the interpretation of the serological tests performed by the laboratory. Because red cell incompatible transfusion reactions occur so infrequently it is difficult to accumulate practical experience in their laboratory presentation and this paper describes several of the pitfalls that may be encountered when laboratory findings deviate from classical descriptions. These include the absence of a positive direct antiglobulin test (Coombs) or an incompatible crossmatch, the absence of any apparent discrepancy between the pre- and post-transfusion specimens in cases of ABO incompatibility, the differentiation of auto-immune haemolytic anaemia from delayed transfusion reactions and the assessment of the clinical significance of any blood group antibodies that may be detected.

ABO Blood-Group System↗

Immediate haemolytic transfusion reaction due to anti-Inb.

An immediate haemolytic transfusion reaction was investigated in a patient with intestinal cancer. The causative antibody was directed against a high-frequency antigen Inb that was presumably produced as a result of pregnancies. This is the first case of a severe transfusion reaction due to this alloantibody.

Adult↗

Fatal blood transfusion reactions. An analysis.

This analysis of fatal blood transfusion reactions includes statistics from the Bureau of Biologics provided through the Freedom of Information Act. The study of 126 reported transfusion fatalities occurring between 1976 and 1980 showed that the staff certifying compatibility and the personnel administering the blood have an approximately equal share of the problems. Resolution of blood bag labeling errors through automation leaves patient identification as a major obstacle to those certifying compatibility and the transfusionists. The patient identification wrist band is excellent. However, professional staff do not always utilize this information, relying on memory. In addition, professional staff do not always collate adequately the information on the blood transfusion request form, the blood bag label, and the wrist band of the patient to be transfused. Electronic collation is discussed as a means to identify discrepancies prior to transfusion. The special problem of staff dealing with a time-limited, life-threatening emergency is described and six critical areas related to the problem of fatal transfusion reactions are suggested for further analysis.

Blood Grouping and Crossmatching↗

Generation of inflammatory cytokines and chemokines from peripheral blood mononuclear cells by HLA Class II antibody-containing plasma unit that was associated with severe nonhemolytic transfusion reactions.

BACKGROUND: HLA Class II antibodies are thought to be involved in severe transfusion reactions including transfusion-related acute lung injury (TRALI). The activation of monocytes by HLA Class II antibody may play an important role in the etiology of TRALI. CASE REPORT: An 81-year-old man with non-Hodgkin's lymphoma (Clinical Stage IIIA) received a plateletpheresis unit containing at least 4 x 10(11) platelets because of thrombocytopenia and a bleeding tendency. Approximately 30 minutes after the start of transfusion, he developed chills, tachycardia, dyspnea, lumber, and abdominal pain and then a fever (40.3 degrees C). His SaO(2) dropped to 70 percent. The transfusion was discontinued immediately. His symptoms disappeared after treatment with oxygen and the administration of corticosteroid and aminophyrine. A chest X-ray showed no sign of pulmonary edema. RESULTS: The donor serum sample had HLA-DR antibodies against multiple DR antigens including DR13, the recipient's HLA-DR type. The cross-match between the patient's lymphocytes and the donor serum was positive. The treatment of peripheral blood mononuclear cells from healthy subjects bearing DR13 antigen with the donor plasma caused the secretion of inflammatory cytokines (i.e., interleukin [IL]-1beta, IL-6, and tumor necrosis factor-alpha) and neutrophil-activating chemokines (i.e., IL-8 and CXCL1/GRO-alpha) in a cognate antigen-antibody relationship. In addition, the secretion of inflammatory cytokines appeared to require the involvement of CD32 and/or CD16. CONCLUSION: HLA-DR antibodies, detected in this case, had biologic functions to induce production of not only inflammatory cytokines but also neutrophil-attractant chemokines in vitro, which could contribute to the etiology of severe nonhemolytic transfusion reactions.

Acute Disease↗

Blood transfusion reactions in Malaysian newborn infants.

A prospective observational study was carried out over a seven month period in the neonatal intensive care unit (NICU) of a large Malaysian maternity hospital to determine the rate of blood transfusion and the incidence of transfusion reactions in newborn infants. During the study period, the rates of blood transfusion was 6.1% (n = 117) of NICU admission or 8.2 per 1,000 live births. The median birth weight of the infants who had received blood transfusion was 1,740 grams (range: 725-4,350), and their mean gestational age was 33.6 weeks (sd = 5.1, range = 24-41 weeks). The median age of infants when they first received blood transfusion was 4.0 days (range: 1-27 days). When compared with infants of birth weight between 3,000 and 3,499 grams, infants of birth weight less than 1,500 grams received significantly higher median number of transfusions per infant, (p < 0.001). The incidence of transfusion reaction was 2.7% (3/110) of all transfused infants or 1.3% (3/223) of all blood transfusions. Febrile nonhemolytic reaction was the only type of transfusion reaction detected during the study period. This study showed that transfusion reactions in newborn infants were not common.

Birth Weight↗