How much residual plasma may cause TRALI?

Although passive infusion of plasma-rich components containing white blood cell (WBC) antibodies are responsible for majority of the reported transfusion-related acute lung injury (TRALI) cases, the minimum volume of residual plasma, which might trigger TRALI, is not known. We report three cases of TRALI where the implicated donor component contained between 10 and 20 mL of residual plasma. Two cases were related to transfusion of red blood cells prepared in optimal additive solution, and the other was related to transfusion of pooled buffy coat platelets. In the latter case, WBC antibodies that matched the patient's human leucocyte antigen (HLA) antigens were only found in one buffy coat donor (female) who contributed a buffy coat for pooled platelets preparation. Plasma prepared from pooling platelets was collected from a male donor. Laboratory investigation confirmed that in all three cases, the donors' serum contained three to four different HLA class 1-specific and class 11-specific antibodies that matched with the patient's HLA type. Our cases suggest that the residual plasma volume as small as 10-20 mL containing donor derived WBC antibodies may cause TRALI. The risk of TRALI remains, despite providing pooled platelets suspended in male donor plasma. The significance of multiple HLA antigen/antibody matching between donor and recipient in immune TRALI warrants further study.     

Ten years of hemovigilance reports of transfusion-related acute lung injury in the United Kingdom and the impact of preferential use of male donor plasma

BACKGROUND AND METHODS: From 1996 through 2006, 195 cases were reported as transfusion-related acute lung injury (TRALI) to the Serious Hazards of Transfusion scheme and from 1999 onward classified by probability, using clinical features and HLA and/or HNA typing. From late 2003, the National Blood Service provided 80 to 90 percent of fresh-frozen plasma (FFP) and plasma for platelet (PLT) pools from male donors.
RESULTS: Forty-nine percent of reports were highly likely/probable TRALI, and 51 percent possible/unlikely. Of 96 investigations, donor antibodies recognizing recipient antigens were found in 73 cases (65%), with HLA Class I in 25 of those (40%), HLA Class II antibodies in 38 (62%), and granulocyte antibodies in 12 (17%). A review in 2003 revealed that the TRALI risk/component was 6.9 times higher for FFP and 8.2 times higher for PLTs than for red blood cells, and that in donors of implicated FFP/PLTs, white blood cell antibodies were found 3.6 times more often than by chance (p ≤ 0.0001), with all implicated donors being female. Provision of male plasma was associated with a reduction in TRALI reports from 36 in 2003 to 23 in each of 2004 and 2005 and 10 in 2006. Highly likely/probable cases reduced from 23 in 2003 to 10, 6, and 4 in the 3 subsequent years, with cases implicating FFP or PLTs falling from 16 to 9, 3, and 1 respectively.
CONCLUSIONS: The risk of highly likely/probable TRALI due to FFP has fallen from 15.5 per million units issued during 1999 through 2004 to 3.2 per million during 2005 through 2006 (p = 0.0079) and from 14.0 per million to 5.8 per million for PLTs.     

Impact of a transfusion-related acute lung injury reduction strategy on apheresis platelet collections

Background: Most blood centers in the US have implemented transfusion‐related acute lung injury (TRALI) mitigation strategies for apheresis platelet (AP) donations based on theoretical impact of donor loss. The aim of this study is to determine the actual impact of a TRALI mitigation strategy in a US blood center. Study Design and Methods: Daily collection events and resulting products were retrospectively obtained before and after implementation of a TRALI reduction strategy (HLA antibody testing female AP donors four or more pregnancies) for comparison. The retention rate of reassigned donors was determined by reviewing whole blood (WB) and/or apheresis red blood cell (AR) donations post reassignment. Data were obtained to compare donor frequency and split rate from reassigned (historical data) and new AP donors. Results: Mean daily collections (27.7 vs. 30.0) and total products (12,211 vs. 12,957) were significantly higher after implementation, but the number of products/collection event was lower (1.49 vs. 1.40). Mean collections/donor/year (4.0 vs. 1.8) and split rate (36% vs. 27%) were historically higher for reassigned (n = 45) versus new AP donors (n = 1,090). Seventy‐three of 112 donors (65%) testing positive for HLA antibodies returned for WB or AR donations, 31 of 45 (69%) active AP donors returned. Conclusions: Donor loss may not be adequate to estimate impact on AP inventory, as donation characteristics may differ between new donors and those reassigned. We show successful implementation of a TRALI mitigation strategy by increasing collection goals and AP donor recruitment efforts beyond donor loss. Retaining the majority of reassigned donors is feasible. J. Clin. Apheresis 2012. © 2012 Wiley Periodicals, Inc.     

Testing only donors with a prior history of pregnancy or transfusion is a logical and cost-effective transfusion-related acute lung injury prevention strategy

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related fatality reported to the Food and Drug Administration. Donor screening may reduce TRALI risk. This study sought to compare the efficacy and safety of different TRALI risk‐reduction strategies at a hospital‐based donor center. STUDY DESIGN AND METHODS: Samples from 1053 donors who answered questions regarding pregnancy and transfusion history were tested for HLA Class I and II antibodies using a flow cytometry–based screening assay. Donor history was compared with the presence of HLA alloantibodies. These data were used to model several TRALI risk‐reduction strategies. The medical records of patients transfused fresh‐frozen plasma (FFP) from highly alloimmunized donors were retrospectively reviewed for TRALI. RESULTS: HLA alloimmunization was observed among 25.4 percent (256/1009) of all female donors and among 12.0 percent (3/25) of those male donors who gave a history of prior transfusion. Prior pregnancy, reported by 52.6 percent (531/1009) of females, correlated significantly with HLA alloimmunization (p < 0.0001). The rate of HLA alloimmunization increased with parity. A positive pregnancy history was a sensitive (87.9%) screen for HLA alloimmunization with a negative predictive value of 93.5 percent (95% confidence interval, 91.3%‐95.7%). Although 5.9 percent (27/459) of nulliparous, untransfused females demonstrated a positive screening test, only 1 percent (7/459) had a confirmed HLA alloantibody. Transfusion of FFP from donors found retrospectively to be highly alloimmunized led to reactions suggestive of TRALI in 2 of 26 recipients. CONCLUSIONS: Donor history is a reliable predictor of HLA alloimmunization. Testing only donors with a prior history of pregnancy or transfusion is a logical and cost‐effective TRALI prevention strategy.     

Prevalence of HLA sensitization in female apheresis donors

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication of plasma-containing blood components. Studies have implicated HLA antibodies along with biologically active lipids in stored blood in the pathogenesis of TRALI. It has been proposed that the exclusion of HLA-untested, multiparous donors of plasma-rich components, including plasma and single-donor apheresis platelets, would substantially reduce the risk of TRALI. STUDY DESIGN AND METHODS: To investigate the feasibility of such an exclusion, 332 female plateletpheresis donors with a record of over 9000 donations, none of which were associated with TRALI, were studied. RESULTS: Seventeen percent of female donors demonstrated HLA sensitization. Parity and HLA sensitization were significantly correlated (p<0.0001), with sensitized donors having an average of 2.9 (+/− 0.6 95% CI) prior pregnancies and unsensitized donors having an average of 1.8 (+/− 0.2 95% CI) prior pregnancies. The percentage of HLA-sensitized women with 0, 1 to 2, and > or = 3 pregnancies was 7.8, 14.6, and 26.3, respectively. CONCLUSION: These findings confirm the hypothesis that multiparous women (> or = 3 pregnancies) represent an increased potential risk for TRALI. However, the exclusion of multiparous plateletpheresis donors would eliminate one-third of our female donor pool. Screening such donors for HLA sensitization may represent the optimal approach for identifying donors at risk for causing TRALI, but this still would result in the deferral of 8 percent of female plateletpheresis donors. At present, prospective screening to identify donors at risk for causing TRALI is not justified.     

Swiss Haemovigilance Data and Implementation of Measures for the Prevention of Transfusion Associated Acute Lung Injury (TRALI)

SUMMARY: In Switzerland, blood donations are collected exclusively from healthy non-remunerated voluntary blood donors mainly by 13 regional Blood Transfusion Services throughout the country. Thereby, self-sufficient blood supply for a population of about 7.5 million is achieved, and approximately 300,000 units of red cells, 75,000 therapeutic units of fresh plasma, and 20,000 therapeutic units of platelets are transfused annually. Reporting to Swissmedic (the Swiss agency for therapeutic products) of all suspected adverse transfusion events on a standardised form is mandatory. Data are then analysed to estimate the risks of the most serious transfusion events. Together with transfusion of an incorrect blood component and bacterial contamination of platelet concentrates, TRALI is a significant risk of transfusion in Switzerland and occurs in approximately every 8,000-20,000 FFP transfusions according to current haemovigilance data. Among 25 reported cases between 2002 and November 2007, 4 are proven immune TRALI, 2 are highly likely immune TRALI, 10 are possibly immune TRALI, 8 are non-immune TRALI, and 1 is a suspected case which could not be confirmed as TRALI. Based on the hypothesis of an immunological trigger of TRALI, an exclusion of the transfusion of plasma from female donors can be considered as a precautionary measure which might have prevented 4 cases of proven immune TRALI, 2 cases of highly likely immune TRALI, and an unknown number of the 10 cases of possibly immune TRALI. Based on these data and encouraging preliminary reports of the effects of comparable measures in other countries, the decision was made that starting with January 1st 2007 the production of quarantined FFP is restricted to donations from men or from women confirming that they have never been pregnant (to their knowledge) or with negative tests for antibodies against HLA class I and II. The analysis of further vigilance data is needed to elucidate the efficacy of this preventive measure.     

Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure

BACKGROUND: Transfusion‐related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. STUDY DESIGN AND METHODS: We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. RESULTS: A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. CONCLUSION: A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI.     

A national survey of transfusion‐related acute lung injury risk reduction policies for platelets and plasma in the United States

BACKGROUND: Little information exists on the specific transfusion‐related acute lung injury (TRALI) risk reduction practices used by multiple blood collecting institutions in the United States. STUDY DESIGN AND METHODS: An AABB‐appointed TRALI working group designed a set of questions about TRALI risk reduction for platelets (PLTs) and plasma. AABB member institutions were asked to respond via an Internet‐based survey during a 3‐week period in August through September 2009. RESULTS: Valid responses were received from 47 US blood centers (accounting for 1.57 million apheresis PLT units and 3.15 million whole blood–derived transfusable plasma units) and 56 hospital blood collectors. Among the blood centers, 87 and 98% had initiated some PLT and plasma risk reduction, respectively. HLA antibody testing of plateletpheresis donors was performed by 20 (43%) blood centers. There was substantial variation in the number of pregnancies (from one to more than four) that triggered testing and most centers did not screen based on a transfusion history. Almost all centers had policies to redirect HLA antibody–positive donors to whole blood donation and to potentially retest HLA antibody–negative donors. There were no blood centers performing HNA antibody testing. Sex‐based risk reduction policies for plasma included all male, or predominantly male, and never‐pregnant females; these varied by blood center, blood group, and method of plasma collection. A majority of centers indicated increased production of plasma frozen within 24 hours after phlebotomy. CONCLUSIONS: Almost 3 years after the publication of the initial AABB bulletin on this issue, TRALI risk reduction strategies are commonly employed at most US blood centers. However, procedures are not uniform.     

Transfusion-related acute lung injury reports in the Netherlands: an observational study

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious, sometimes fatal complication of transfusion, attributed to white blood cell (WBC)-reactive antibodies present in the blood product. This study investigated incidence and etiology in the Netherlands.
STUDY DESIGN AND METHODS: From January 2005 through July 2007, all TRALI cases reported to the Sanquin Blood Banks were evaluated. Only cases meeting the Canadian Consensus Conference criteria for TRALI were included and investigated for patient, donor, and product characteristics. Patients and donors were screened for HLA Class I, HLA Class II, and granulocyte antibodies.
RESULTS: A total of 56 TRALI cases were reported of which 49 were completely evaluated. Seventy-eight percent of the patients needed monitoring or mechanical ventilation on the intensive care unit, 10 patients died. In 61% of cases large-volume plasma products were involved. WBC-reactive antibodies in donors were found in 73% of cases, with proven incompatibility in 21 of 44 (48%) investigated cases. Possible TRALI cases, as defined by the Canadian Consensus Conference, had significantly lower incompatibility rates compared to TRALI cases, 18% versus 58% (p = 0.036). In the 21 alloimmune cases, a total of 31 implicated donors were found, of which 26 were female, including 12 fresh-frozen plasma (FFP) products.
CONCLUSION: TRALI is the most serious transfusion complication in the Netherlands, causing severe morbidity and mortality. Antibodies were found in the majority of the cases, but causality with proven incompatibility could be established in 21 cases (48%). Female FFP products were involved in 57% of proven alloimmune cases and would theoretically be prevented using male FFP only.     

Establishing assay cutoffs for HLA antibody screening of apheresis donors

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related deaths. Donor HLA antibodies have been implicated in TRALI cases. Blood centers are implementing TRALI risk reduction strategies based on HLA antibody screening of some subpopulations of ever‐pregnant apheresis platelet (PLT) donors. However, if screening assay cutoffs are too sensitive, donation loss may adversely impact blood availability. STUDY DESIGN AND METHODS: Pregnancy history and HLA antibody screening and single‐antigen bead data from blood donors in the Retrovirus Epidemiology Donor Study‐II Leukocyte Antibody Prevalence Study were evaluated for correlations between assay screening values, HLA antibody titer, and number of HLA antigen specificities. The probabilities of matching a cognate antigen in a recipient were calculated and examined in association with total number of specificities observed and screening values. The relative impact of imposing various screening assay cutoffs or pregnancy stratification was examined in relation to detection of HLA antibody–reactive donations and loss of donors and donations. RESULTS: We provide evidence that higher HLA antibody screening assay values are associated with maintaining higher screening signals upon dilution and an increased breadth of specificities compared with lower screening values; the latter correlated with an increased risk of a cognate antigen match in potential recipients. Depending on the TRALI risk reduction strategy used, the potential loss of donations ranged between 0.9 and 6.0%. CONCLUSION: This analysis should enable blood centers to decide upon a TRALI risk reduction strategy for apheresis PLTs that is consistent with how much donation loss the blood center can tolerate.     

Transfusion-Related Acute Lung Injury: Incidence, Pathogenesis and the Role of Multicomponent Apheresis in Its Prevention

SUMMARY: Although transfusion-related acute lung injury (TRALI) is now appreciated as the most common cause of death from transfusion, its incidence remains unknown. The most frequently cited figure is 1:5,000 plasma-containing components. Certain patient groups may be at significantly higher risk. TRALI is both underdiagnosed and un-derreported. It is misdiagnosed as transfusion-associated circulatory overload. Several mechanisms have been proposed for its pathogenesis-leukocyte antibodies and the 2-hit model. These may overlap, and both involve transfusion of leukocyte antibodies. Passive transfusion of leukocyte antibodies is strongly associated with TRALI; these are identified in 60-85% of cases. Multiparous blood donors are the most frequent source of these antibody-containing components. The antibodies are HLA class I and II and/or granulocyte-specific. In 50% of cases the antibody corresponds to an epitope in the patient. HLA class I antibodies have been shown to prime and activate neutrophils. Clinical reports and animal models link HNA-3a antibodies with severe lung injury. A number of TRALI prevention and risk mitigation strategies have been proposed. In the UK and the USA, these strategies have centered upon excluding 'high risk' (HLA/HNA antibody containing) plasma from fresh frozen plasma and platelet products. Multicomponent apheresis collection of platelets, plasma and red blood cells is a means of accomplishing this objective.     

The impact of policies to restrict the use of plasma containing products and apheresis platelets from female donors to mitigate transfusion related acute lung injury (TRALI) in Brazil

Background and ObjectivesAlthough the incidence of TRALI is unknown in Brazil, some blood centers have adopted strategies to prevent TRALI. We evaluated the impact of three policies to mitigate TRALI on the supply of blood products: to divert the production of whole blood-derived plasma from female donors; to defer all female donors from apheresis platelet collections, and to defer only multiparous female donors from apheresis platelet collections.Materials and MethodsData from allogeneic whole blood and apheresis platelet donations from April 2008 to December 2009 were collected in three Brazilian blood centers and the impact of the aforementioned strategies was evaluated.ResultsOf 544,814 allogeneic blood donations, 30.8% of whole blood plasma and 24.1% of apheresis platelet donations would be reduced if only male donor plasma was issued for transfusion and all female donors were deferred from apheresis donation, respectively. If only multiparous donors were deferred from apheresis donation, there would be a 5% decrease of all apheresis platelet collections.ConclusionRestricting the use of whole blood derived plasma to male-only donors and deferring all female apheresis platelet donors would impact two out of three Brazilian blood centers. A deferral policy on multiparous apheresis platelet donors may be acceptable as a temporary measure, but may cause more stress on a system that is already working at its limit.     

White blood cell-reactive antibodies are undetectable in solvent/detergent plasma

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Although all types of blood products have been associated with TRALI, fresh-frozen plasma (FFP) is the most commonly implicated component. It has been postulated that TRALI is an immune-mediated event, because white blood cell (WBC)-reactive antibodies in the donor's plasma are frequently associated with the syndrome. In contrast to single donor-derived FFP, solvent/detergent (S/D) plasma is produced from multiple donations, leading to an at least 500-fold dilution of a single plasma unit. It was hypothesized that WBC-reactive antibodies are undetectable in S/D FFP. STUDY DESIGN AND METHODS: Twenty batches of S/D FFP (5 of each ABH group) were analyzed with well-established routine techniques to detect WBC antibodies. RESULTS: All samples tested negative for granulocyte-specific as well as HLA Class I and Class II antibodies. CONCLUSIONS: Different strategies to reduce the risk of TRALI are currently discussed. These include screening of all potentially immunized donors for WBC-reactive antibodies and exclusion of multiparous or all women from donating FFP. Here, it is demonstrated that neither granulocyte- nor lymphocyte-reactive antibodies are detectable in S/D FFP. Thus, S/D FFP may represent a potential alternative to reduce the risk of TRALI associated with the transfusion of FFP.     

Single hospital experience of TRALI

BACKGROUND: TRALI is a serious adverse effect of blood transfusion. There is evidence that the condition is underrecognized and underreported. STUDY DESIGN AND METHODS: This study was an observational study carried out in a single hospital. RESULTS: Eleven cases of TRALI were recognized over 12 years. In 10 cases the implicated donor unit was FFP and in 1 case uncertain. All implicated donors were parous women. In 4 cases the presumed causative antibodies were to an HLA class II antigen only. Specific anti-neutrophil antibodies, possibly causative, were detected in 1 case only. Ten of the 11 cases required mechanical ventilatory support. Five persons died as a result of the TRALI. The observed incidence of TRALI caused by FFP is 1 in 7900 units transfused. CONCLUSION: TRALI is the most common serious adverse effect of blood transfusion in our hospital. Antibodies to HLA class II antigens should be looked for routinely when investigating a possible case of TRALI.     

Recurrent transfusion-related acute lung injury after a two-year interval

Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion. The epidemiology and pathogenesis of TRALI are not well established. A Medline literature search shows only rare reports of recurrent TRALI, all occurring soon after the first episodes. We report a case of recurrent TRALI after a 2-year interval. A patient developed TRALI after transfusion of 4 units of fresh frozen plasma for gastrointestinal bleeding due to oesophageal varices in September 2002. The patient required mechanical ventilation but recovered completely. Two years later, in October 2004, the patient experienced a second episode of TRALI during liver transplantation for hepatitis C virus /alcoholic cirrhosis. Again, the patient recovered after ventilator support. Laboratory investigation of the first TRALI episode (2002) showed antibodies against class II human leukocyte antigens (HLA) in three female donors. Laboratory investigation of the second episode (2004) showed anti-DR52 (HLA class II) antibodies in one female donor matching the DR-52 HLA class II antigen in the recipient. TRALI can rarely recur. Consideration of future blood needs for patients experiencing recurrent TRALI should include preventive measures against further TRALI reactions, such as blood from male donors or blood less than 14 days old.     

Screening for antibodies to HLA class I in apheresis donors following Covid‐19 or SARS-CoV-2 vaccination

Transfusion of HLA-specific antibodies may play a role in induction of TRALI, the transfusion complication responsible for most transfusion-related deaths. In Oslo, we screen our apheresis donors and defer HLA-immunized donors from donation of plasma-rich blood components. During the second year of the Covid-19 pandemic and following the first months of SARS-CoV-2 vaccination, both the virus itself and the vaccines were suspected of inducing de novo production of antibodies to HLA class I in patients. For the blood center, the possibility of finding HLA-antibodies in an increased number of blood donors has serious implications. We therefore conducted a study to map the extent of de novo HLA-specific antibodies in representative donor groups. 106 apheresis donors were screened for antibodies to HLA class I/II following Covid-19 or vaccination with either mRNA or adenovirus-vector vaccines, and the findings were compared to pre-Covid blood samples from the same donors. In addition, we analyzed pre-Covid samples from 11 HLA-antibody-positive donors of Covid convalescence plasma. Only three established thrombapheresis donors were deferred due to vaccine-induced HLA-antibodies. In short, our findings did not support the hypothesis that SARS-CoV-2 virus or vaccination cause de novo HLA immunization in healthy blood donors. However, some donors with pre-existing antibodies showed increased antibody expression, confirming a general boost of the immune response following infection or vaccination.     

Transfusion-related acute lung injury surveillance (2003-2005) and the potential impact of the selective use of plasma from male donors in the American Red Cross

BACKGROUND: American Red Cross surveillance data on transfusion-related acute lung injury (TRALI) fatalities were analyzed to evaluate the association with components from donors with white blood cell (WBC) antibodies and to examine the potential impact of the selective transfusion of plasma from male donors. STUDY DESIGN AND METHODS: Suspected TRALI reports in 2003 through 2005 were identified and all fatalities were reviewed and classified by three physicians as "probable TRALI" or of "unrelated etiology," with independent review of the associated serologic investigation. Hospital investigational and reporting biases could not be fully controlled in this retrospective study. RESULTS: A total of 550 reports of suspected TRALI, including 72 fatalities, were investigated. The number of reports increased each year and the rate varied by geographic region. Retrospective review of fatalities revealed 38 cases of probable TRALI, the majority (24 of 38 [63%]) after plasma transfusion. A female, WBC antibody-positive donor was involved in 71 percent (27 of 38) of cases and in 75 percent (18 of 24) of cases involving plasma transfusion. Female antibody-positive donors were more likely to be associated with probable TRALI than with unrelated cases (p = 0.0001; odds ratio [OR], 9.5; 95% confidence interval [CI], 2.9-31.1]. The rate of probable TRALI among recipient fatalities was higher for plasma components (1:202,673; OR, 12.5; 95% CI, 5.4-28.9) and apheresis platelets (PLTs; 1:320,572; OR, 7.9; 95% CI, 2.5-24.8) compared to red cells (1:2,527,437). Male donors contributed 64.5 and 52.0 percent of distributed apheresis PLTs and plasma components, respectively, in 2005. CONCLUSION: Plasma components linked to female donors with WBC antibodies were responsible for the majority of probable TRALI fatalities. Prudent measures to limit transfusion of WBC antibody-containing plasma components may prevent as many as six fatalities per year in the Red Cross system.     

Identification of specificities of antibodies against human leukocyte antigens in blood donors

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related mortality. Blood centers are implementing TRALI risk reduction strategies based on screening apheresis donors for antibodies to human leukocyte antigens (HLA). STUDY DESIGN AND METHODS: HLA antibody screening was performed on 7920 blood donors from the Leukocyte Antibody Prevalence Study (LAPS) using Luminex‐based normalized background (NBG) cutoff ratios of 10.8 (Class I) and 6.9 (Class II). Single antigen bead (SAB) assay cutoffs of 2500 median fluorescence intensity units (Class I) and 1500 (Class II) were established based on results of two subpopulations of LAPS donors. Antibody frequencies against HLA A, B, C, DR, DQ, and DP antigens were determined for screen‐reactive donors with prior pregnancies. RESULTS: SAB reactivity for samples above our multiantigen bead NBG cutoffs was 78% for Class I and 79% for Class II. The SAB‐positive rate increased among women with zero to four or more pregnancies (0.3%‐15.6% Class I and 0.4%‐18% Class II; p < 0.00001). The highest frequency antibodies were DR11 and B15 (4.4% of women with prior pregnancies). The majority of Class I positives contained more than five specificities. For Class II, antibody‐positive women segregated into two groups: a single specificity or more than five specificities. CONCLUSIONS: Identification of HLA antigen specificities supports pregnancy associations previously found with screening assays. The significance of particular HLA specificities for inducing TRALI is currently being evaluated in a large lookback study of recipients of high‐plasma‐volume components from this donor cohort.     

Impact of using different laboratory assays to detect human leukocyte antigen antibodies in female blood donors

BACKGROUND: HLA antibodies passively transferred to transfused recipients may cause transfusion reactions such as transfusion‐related acute lung injury (TRALI), but in many of the reported TRALI incidents, no white blood cell antibodies have been identified. We investigated whether a higher number of anti‐HLA would be detected in donor's plasma by using a method with potential higher sensitivity rate. STUDY DESIGN AND METHODS: Sera from 300 previously pregnant female blood donors were screened for anti‐HLA using a solid‐phase mixed‐antigen assay (enzyme‐linked immunosorbent assay [ELISA]). Samples from 60 women with three or more pregnancies with a negative ELISA were further tested using microbead‐flow assays (LABScreen mixed, panel‐reactive antibodies [PRA], and single antigen). RESULTS: Anti‐HLA Class I and/or Class II were detected by ELISA in 26.7% (80/300) of all women and in 37.0% (37/100) of women with three or more pregnancies. The LABScreen assays detected additional anti‐HLA specificities (44 Class I and 17 Class II) in 28.3% (17/60) of ELISA‐negative donors with three or more pregnancies. HLA antibodies were detected in 8.3% (5/60), 18.3% (11/60), and 21.7% (13/60) of ELISA‐negative women by LABScreen mixed, PRA, or single antigen, respectively. CONCLUSION: Our data showed that the microbead‐flow detected more HLA antibodies than ELISA, but the clinical significance of these antibodies is currently unknown. Detecting anti‐HLA is useful for donor management and could contribute to the decision to definitively defer blood donors involved in TRALI incidents. However, further studies are necessary to better determinate the relative risk of TRALI induced by anti‐HLA detected only by techniques with higher sensitivity rate.     

TRALI risk reduction: Donor and component management strategies

Transfusion‐related lung injury (TRALI) occurs in ～1 in 5,000 transfusions and may cause considerably more morbidity and mortality that is not recognized in clinical practice. Based on the current understanding of the etiology of TRALI, blood centers have implemented or are evaluating various donor and component management strategies in an effort to mitigate the risk of TRALI. Many cases of TRALI are likely caused by antibodies to leukocyte antigens (HLA or HNA) in blood components. Approximately 10 to 20% of female blood donors with a history of pregnancy and 1 to 5% of male blood donors harbor these antibodies. Alternatively, TRALI may be mediated by other bioactive lipids or substances that accumulate during storage and cause a reaction when transfused to susceptible patients. The complex interplay among various donor‐, component‐, and patient‐related factors underlying TRALI guarantees that effective prevention will not be a single or simple intervention but rather will require a multifaceted approach. Perhaps, the most important risk reduction strategy is the effort to ensure appropriate use of blood products and eliminate unnecessary transfusions. Blood collection agencies, however, have more proximate control over donor selection and component management than transfusion practice. AABB has provided some guidance on deferring donors implicated in TRALI and minimizing the preparation of high plasma volume components from donors who have anti‐leukocyte antibodies or are at increased risk of leukocyte alloimmunization. Blood centers have taken various approaches to mitigate the risk of TRALI, and the possible benefit and the inherent limitations of the current strategies will be reviewed. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.