Risk Of Transfusion-related Acute Lung Injury Research Articles

Storage time of blood products and transfusion‐related acute lung injury

Besides white blood cell antibodies in plasma-rich products, another cause of transfusion-related acute lung injury (TRALI) could be release of biologically active substances during storage of cellular blood products. We aimed to investigate the association of storage time and risk of TRALI for different product types. We compared storage time of blood products transfused within 6 hours before the onset of TRALI to storage time of a representative sample of all blood products transfused in the Netherlands. Generalized linear models were used to correct for confounding variables. Platelets (PLTs) in plasma transfused to TRALI patients were stored for 0.7 (95% confidence interval [CI], 0.073 to 1.3) days longer than those transfused to controls. The relative risk of TRALI, after receiving PLTs stored for 4 or 5 days, compared to 3 days or less, was 5.8 (95% CI, 0.99 to 110) and increased to 6.3 (95% CI, 1.1 to 118) after more than 5 days (i.e., 6 or 7 days). While longer storage of buffy coat-derived PLTs was associated with an increased risk of TRALI, storage of plasma for up to 2 years and red blood cells for up to 35 days was not associated with the risk of TRALI.

Transfusion‐related acute lung injury investigation insights

Background From 2005 to 2009 transfusion‐related acute lung injury (TRALI) has maintained its ranking as the number one cause of transfusion‐related fatalities reported to the FDA. This confirms that TRALI remains a serious and potentially fatal transfusion complication. As over 80% of TRALI events have been attributed to donor derived leucocyte antibodies the detection and management of donors with these antibodies is crucial to reducing the TRALI risk.Objective Because blood is a precious medical commodity in limited supply, it would be more effective to exclude only those donors with a risk of triggering TRALI substantiated by objective laboratory evidence (i.e. implicated). This would allow implicated donors to be confidently excluded and would allow other donors only clinically associated with TRALI to be reassessed for continuing to donate. Therefore, the design of an effective and objective TRALI laboratory investigation strategy has to be based on current knowledge of the mechanism of antibody mediated TRALI.Discussion Leucocyte antibodies in the transfused blood product are thought to activate neutrophils in the pulmonary microvasculature. The by‐products of neutrophil activation (e.g. reactive oxygen species and enzymes) consequently cause injury to the pulmonary microvasculature resulting in respiratory distress. There is strong evidence for the role of neutrophil reactive antibodies to human neutrophil antigen (HNA)‐3a and human leucocyte antigen (HLA)‐A2 in serious TRALI events. HLA Class II antibodies have also been implicated and they are thought to activate monocytes, which subsequently activate neutrophils. Neutrophils, which express human neutrophil antigens (HNA) and HLA Class I, are thus key effector cells in TRALI injury. Because of the pivotal role of neutrophils, effective TRALI investigations must include well validated neutrophil assays such as the granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT).This article will discuss:– TRALI investigation strategy,– assays for detection of antibodies to HNA and HLA,– how to differentiate associated from implicated donors,– and provide thoughts on the remaining 20% of TRALI events (i.e. non‐immune mediated).

The Leukocyte Antibody Prevalence Study-II (LAPS-II): a retrospective cohort study of transfusion-related acute lung injury in recipients of high-plasma-volume human leukocyte antigen antibody-positive or -negative components.

We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI. In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of 2596 plasma-rich blood components (transfusable plasma and plateletpheresis) sent to participating hospitals; half of the components were collected from anti-HLA-positive donors (study arm) and half from anti-HLA-negative donors (control arm) matched by sex, parity, and blood center. A staged medical record review process was used. Final recipient diagnosis was based on case review by a blinded expert panel of pulmonary or critical care physicians. TRALI incidence was 0.59% (seven cases) in study arm recipients versus 0.16% (two cases) in control arm recipients for an odds ratio (OR) of 3.6 (95% confidence interval [CI], 0.7-17.4; p = 0.10). For possible TRALI cases (nine study arm, eight control arm), the OR was 1.2 (95% CI, 0.4-3.0; p = 0.81), and for TRALI and possible TRALI aggregated together, it was 1.7 (95% CI, 0.7-3.7; p = 0.24). Transfusion-associated circulatory overload incidence was identical in the two arms (1.17 and 1.22%, respectively; OR, 1.0; p = 1.0). TRALI incidence in recipients of anti-HLA-positive components was relatively low for a lookback study (1 in 170) and was higher than in the control arm, but did not reach significance. Based on this trend, the data are consistent with the likelihood that TRALI risk is decreased by selecting high-volume plasma components for transfusion from donors at low risk of having HLA antibodies.

Alloexposed blood donors and transfusion‐related acute lung injury: a case‐referent study

Donor white blood cell (WBC) antibodies are thought to increase the risk of transfusion-related acute lung injury (TRALI). WBC antibodies can be present in blood products from donors who have been alloexposed. Alloexposed donors are increasingly excluded from donating plasma, but can still donate plasma-poor products. We aimed to quantify the contribution of alloexposed donors to the occurrence of TRALI for different blood product types. We performed a case-referent study including all reported TRALI patients and all Dutch blood donors. Data on alloexposure status of donors of all TRALI cases reported between January 2004 and October 2008, in the Netherlands, were compared to information on the total donor population. Alloexposure status of all 223 involved donors was compared to the expected status. The overall percentage of TRALI cases that could have been prevented by the deferral of all alloexposed donors (i.e., population-attributable risk [PAR]) was 51% (95% confidence interval [CI], 14%-88%). In 19 recipients of exclusively plasma-poor products (mostly red blood cells [RBCs]), alloexposure of the donors was not associated with TRALI, while in 28 recipients of both plasma-poor and plasma-rich products (>200 mL plasma), the PAR was 94% (95% CI, 34%-100%). Alloexposed donors conferred an increased risk of TRALI in recipients of plasma-rich products, but not in recipients of plasma-poor products. Although WBC antibodies are an important risk factor for TRALI, among RBC recipients another risk factor must be more important.

Is it time to reconsider neutrophil antibody testing of platelet donors?

Is it time to reconsider neutrophil antibody testing of platelet donors?

Analysis of cutoffs for screening sensitized blood donors for HLA alloantibodies using a cytometric microbead assay

Cytometric-based microbead assays for HLA alloantibodies may be effective tools for transfusion-related acute lung injury (TRALI) risk reduction. However, the optimal cutoff for donor screening is unclear. To optimize the screening test cutoff in sensitized donors, sera were screened with a cytometric microbead assay. Confirmatory testing was performed on samples with a normalized background (NBG) ratio of 2.4 or more. Sera with a NBG of 2.4 to 9.9 had positive predictive values (PPVs) of 78.2% (95% confidence interval [CI], 67.8%-86.0%) and 71.1% (95% CI, 56.5%-82.4%) for Class I and II antibodies, respectively. Sera with a NBG of 10 or more had PPVs of 98.9% (95% CI, 93.3%-100%) and 99.1 (95% CIs, 94.7%-100%) for Class I and II, respectively. The percent panel-reactive antibody (PRA) of confirmed HLA alloantibodies from sera with a NBG of 2.4 to 9.9 was 29.3±17% (mean±standard deviation) for Class I and 22.3±16.7% for Class II, but for antibodies from sera with a NBG of 10 or more the PRAs were 65.3±24.0 and 64.1±25.2% for Class I and II, respectively (p<0.00001). Serial dilution studies comparing the screening test with antiglobulin-enhanced lymphocytotoxicity suggested that NBG correlated with antibody titer. In our center, deferral for prior pregnancy or transfusion would result in loss of 28.8% of apheresis platelet (PLT) donors. Using the screening test at a cutoff of 2.4 or more or 10 or more would reduce the fraction of donors lost to 12.7 or 8.0%, respectively. A screening cutoff of 10 or more predicts HLA alloimmunization in sensitized donors and is associated with higher PRAs and titers. Implementation of this cutoff may reduce TRALI risk while limiting unnecessary deferral of PLT donors.

Effective reduction of transfusion-related acute lung injury risk with male-predominant plasma strategy in the American Red Cross (2006-2008)

Effective reduction of transfusion-related acute lung injury risk with male-predominant plasma strategy in the American Red Cross (2006-2008)

Transfusion-Related Acute Lung Injury After Transfusion of Maternal Blood

This is a single-center retrospective case-control study of 7 transfusion-related acute lung injury (TRALI) cases and 28 controls in the pediatric spinal surgery population. To determine the association between maternal transfusion and risk of TRALI in pediatric spinal surgery patients. Previous studies support a "2-hit" model for the pathogenesis of TRALI-activation and sequestration of neutrophils in the pulmonary vasculature followed by transfusion of a biologic response modifier such as antileukocyte antibodies. Maternal donation of blood products is a potential risk factor for TRALI because of the development of antileukocyte antibodies during pregnancy. Until now there have been no studies specifically addressing the risk of TRALI following maternal transfusions. This is a retrospective case-control study of 7 TRALI cases with 4 controls per case, matched by strata for volume of plasma transfused. All cases identified by the Transfusion Biology and Medicine Specialized Center of Clinically Oriented Research with a TRALI diagnosis were eligible for inclusion. Electronic medical records and operative notes were reviewed to obtain demographic data, diagnosis, surgical approach, and number of spine levels for each operation. An increased prevalence of maternal blood transfusion was found among the TRALI cases compared with the control cases: 43% (3 of 7) versus 7% (2 of 28), P = 0.044. There were otherwise no statistical differences between the groups, including age, gender, surgical approach, number of spinal levels, or type of blood product transfused. Pediatric patients undergoing spinal surgery may be at increased risk for the development of TRALI following the transfusion of maternal blood products. Accordingly, we recommend that directed donation of maternal blood products should be avoided in this population. This study also found that TRALI may be underrecognized and underreported to the transfusion service.

Female donors and transfusion‐related acute lung injury

Although quantitative evidence is lacking, it is generally believed that the majority of cases of transfusion-related acute lung injury (TRALI) are caused by female blood donors. We aimed to examine the relation between female donors and the occurrence of TRALI. We performed an international, multicenter case-referent study. TRALI patients who were diagnosed clinically, independent of serology or donor sex, and had received transfusions either only from male donors or only from female donors (unisex cases) were selected. The observed sex distribution among the donors of these TRALI patients was compared to the expected sex distribution, based on the relevant donor populations. Eighty-three clinical TRALI cases were included; 67 cases received only red blood cells (RBCs), 13 only plasma-rich products, and three both. Among RBC recipients the relative risk (RR) of TRALI after a transfusion from a female donor was 1.2 (95% confidence interval [CI], 0.69-2.1) and among plasma-rich product recipients the RR was 19 (95% CI, 1.9-191). The p value for the difference between RBCs and plasma was 0.023. Our data support the notion that plasma from female donors is associated with an increased risk of TRALI, while RBCs from female donors are not.

Atypical Respiratory Distress and Transient Decrease in Absolute Neutrophils Associated With Fresh Frozen Plasma Transfusion: Table 1

Background: Transfusion-related acute lung injury (TRALI) is a clinical diagnosis of exclusion to explain acute respiratory distress following a transfusion. Post-transfusion decrease in absolute neutrophils can increase clinical suspicion for this entity. Case Report: Acute respiratory distress requiring intubation occurred following the transfusion of 1 unit of fresh frozen plasma (FFP) to reverse Coumadin in a 65-yearold male. Radiographs were negative for pulmonary infiltrates, and there were no electrocardiography (EKG) changes or clinical indications of volume overload with the clinical assessment being respiratory distress related to transfusion. Sequential complete blood counts showed transient 27-hour decrease in absolute neutrophils and weak reacting neutrophil antibodies in the never transfused male donor. Conclusion: Acute respiratory distress with no bilateral pulmonary infiltrates differentiates this case from TRALI. A male donor with no history of transfusions (not traditionally considered a TRALI risk) was found to have neutrophil antibodies. We therefore suggest that physicians consider (1) investigating cases not meeting full TRALI criteria and (2) testing donors with no risk for human leukocyte antigen (HLA)/neutrophil antibodies.

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

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). 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. 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. 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.

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

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. 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. 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. 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.

Prevalence of HLA antibodies in remotely transfused or alloexposed volunteer blood donors

HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized. Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics. A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80-3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%-11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68-12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07-1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI, -0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously. Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.

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

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. 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). 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. 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.

Risk factors and outcome of transfusion-related acute lung injury in the critically ill: A nested case–control study*

To determine the incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of critically ill patients. In a retrospective cohort study, patients with transfusion-related acute lung injury were identified using the consensus criteria of acute lung injury within 6 hrs after transfusion. Inclusion criterion was a length of intensive care unit admission >48 hrs. Patients developing transfusion-related acute lung injury were matched (on age, sex, and admission diagnosis) to transfused control subjects and patients developing acute lung injury from another origin. Tertiary referral hospital. All first-admitted patients from November 1, 2004, until October 1, 2007, to the intensive care unit. None. Of 5208 admitted patients, 2024 patients had a length of stay >48 hrs, of whom 109 were suspected transfusion-related acute lung injury cases. Compared with transfused control subjects, risk factors for transfusion-related acute lung injury were emergency cardiac surgery (odds ratio, 17.6 [1.8-168.5]), hematologic malignancy (odds ratio, 13.1 [2.7-63.8]), massive transfusion (odds ratio, 4.5 [2.1-9.8]), sepsis (odds ratio, 2.5 [1.2-5.2]), mechanical ventilation (odds ratio, 3.0 [1.3-7.1], and high Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1 [1.0-1.1]; p < .03 for all). The volume of platelets and plasma transfused was associated with transfusion-related acute lung injury in the univariate analysis. However, this association disappeared in the multivariate analysis. Compared with acute lung injury control subjects, risk factors for transfusion-related acute lung injury were sepsis (odds ratio, 2.4 [1.1-5.3]) and high Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1 [1.0-1.1]), whereas pneumonia (odds ratio, 0.4 [0.2-0.7]) was a negative predictive factor. Patients with transfusion-related acute lung injury had a longer duration of mechanical ventilation compared with transfused control subjects and acute lung injury control subjects (231 [138-472] vs. 71 [46-163] and 70 [42-121] hrs, p < .001). Also, 90-day survival of patients with transfusion-related acute lung injury was lower compared with transfused control subjects and acute lung injury control subjects (53% vs. 75% and 83%, p < .02). Transfusion-related acute lung injury is common in critically ill patients. Transfusion-related acute lung injury may contribute to an adverse outcome associated with transfusion. This study identifies transfusion-related acute lung injury risk factors, which may aid in assessing the risks and benefits of transfusion in critically ill patients.

Characterization of the human neutrophil alloantigen-3a

Transfusion-related acute lung injury (TRALI) is a frequent cause of transfusion-associated morbidity and mortality. Severe TRALI is often due to antibodies in blood components directed against the human neutrophil alloantigen-3a (HNA-3a). We show here that the HNA-3a antigen arises from a nucleotide polymorphism in the choline transporter-like protein-2 gene (SLC44A2), with the resulting variation at amino acid position 154 determining the reactivity of the protein with HNA-3a-specific antibodies; the variant with an arginine at this position, rather than a glutamine, constitutes the HNA-3a antigen. The molecular identification of this antigen should facilitate the development of assays for blood donor screening to lower the risk of TRALI.

COMMENTARY: Relative safety of pooled whole blood–derived versus single‐donor (apheresis) platelets in the United States: a systematic review of disparate risks

Risks of transfusion-transmitted infections (TTIs), transfusion-associated sepsis (TAS), and transfusion-related acute lung injury (TRALI) were compared between pooled whole blood-derived (PWBD) and single-donor platelets (PLTs) transfused in the United States. The literature was searched for estimates of the risk of TTIs and TAS and of the effect on bacterial contamination of PLTs of process improvements, bacterial culture, and surrogate methods to detect bacteria. Seven studies published between January 2005 and December 2008 and comparing bacterial contamination frequency between PWBD and single-donor PLTs after implementing bacterial culture testing of both components were subjected to meta-analysis. The three retrieved studies diagnosing TRALI based on the 2004 consensus definition in settings transfusing both PWBD and single-donor PLTs were not amenable to meta-analysis and were assessed qualitatively. Under a best-case scenario, if 100% (from the current 12.5%) of PLT doses were provided as PWBD PLTs, the number of additional transmissions of human immunodeficiency virus, hepatitis C virus, hepatitis B virus, bacteria, or a novel pathogen annually could be 1.2, 1.3, 9.0, 105.3, or 69.2 to 252.6, respectively. Compared with single-donor PLTs, US PLT pools of five concentrates have a 5.6-fold higher risk of bacterial contamination (summary odds ratio, 5.58; 95% confidence interval, 2.60-11.98; p < 0.05). The three studies that diagnosed TRALI based on the consensus definition did not demonstrate a difference in risk between PWBD and single-donor PLTs. TTIs and TAS determine the relative safety of PWBD versus single-donor PLTs. The available limited data do not support a higher risk of TRALI from single-donor (compared with PWBD) PLTs.

Platelet Contamination in Plasma: a Possible Source of Biologic Mediators Linked to Transfusion-Related Acute Lung Injury.

Abstract 2109Poster Board II-86Introduction: Transfusion of plasma is associated with the highest risk of transfusion related acute lung injury (TRALI)-related death. We hypothesize that the current preparation regimen of plasma derived from whole blood has led to significant platelet contamination of plasma, and these platelets contribute to the high rates of TRALI in recipients of plasma. Materials and Methods: Ten units of whole blood were drawn from volunteer donors (5 females and 5 males). All units were centrifuged at 5,316g for 6 minutes to achieve acellular centrifugal effect (ACE) of 4.61×107 in accordance with the blood center's operating procedure for the primary separation of red cells from plasma. We divided each unit into 4 equal aliquots and compared 4 preparation regimens to evaluate the effect of freezing and cell depletion centrifugation (CDC) on platelets and associated factors: not frozen/no CDC, frozen/no CDC, not frozen/CDC, and frozen/CDC. CDC samples were centrifuged at an additional 12,500g for 7 minutes at 4°C to achieve cell depletion prior to freezing, and frozen samples were prepared according to the American Association of Blood Banks (AABB) standard for the preparation of frozen plasma. For each of the four preparation regimens we measured platelet levels using a Beckman Coulter Counter (model: AcT 5Diff AL). We also measured levels of four biologic mediators associated with platelets using commercially available ELISA kits: adenosine diphosphate (ADP), which is found in dense bodies; soluble CD40 ligand (sCD40L), which is found on the surface of platelets; vascular endothelial growth factor (VEGF) and platelet factor 4 (PF4), both found in the alpha granules. Results: We found significant platelet contamination (p<0.05) in the samples that did not undergo CDC with a mean platelet count of 38.8×103/μL (SEM ± 3.0, n=20) versus CDC samples which had a mean platelet count of 1.8×103/μL (SEM ± 0.9, n=20). Samples which had undergone both freezing and CDC had significantly lower levels of VEGF, sCD40L, and PF4 (p<0.05) than samples that had not undergone either process (Table 1). Conclusions: In our study, there was a direct correlation between the concentration of platelet-derived factors and platelet counts in plasma samples. Freezing plasma did not result in a significant decrease in platelet count, but was associated with a decrease in sCD40L. Performing the cell depletion centrifugation resulted in significant decreases in platelet count as well as sCD40L, VEGF, and PF4 levels. Finding a mechanism to reduce platelet contamination of frozen plasma may mitigate TRALI risk by decreasing the levels of biologic mediators, such as sCD40L, implicated in some cases of TRALI.PreparationsCD40L (ng/mL)VEGF (pg/mL)PF4 (ng/mL)ADP (nmol/μL)Not Frozen, No CDC0.930 ± 0.138 †0.087 ± 0.00651.160 ± 2.9420.065 ± 0.006Not Frozen, CDC0.230 ± 0.106 *†0.072 ± 0.00828.820 ± 3.810 *†0.064 ± 0.006Frozen, No CDC0.388 ± 0.104 *0.083 ± 0.00647.310 ± 1.7190.069 ± 0.007Frozen, CDC0.127 ± 0.108 *†0.059 ± 0.006 *†34.260 ± 3.561 *†0.069 ± 0.009Table 1. The data is expressed as the mean ± SEM in pg/ml or ng/ml of the measured biologic mediators from 10 units of plasma each prepared in 4 different ways;*= p<0.05 significance when compared to the not frozen, not CDC sample;†= p<0.05 significance when compared to the frozen, not CDC sample. Disclosures:No relevant conflicts of interest to declare.

The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy.

Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion-related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined. A total of 8171 volunteer blood donors were prospectively recruited by six US blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion and a sample for HLA Class I and II antibody testing by multiantigen bead flow analysis. A total of 8171 donors were enrolled; 7920 (96.9%) had valid HLA antibody test results and 7841 (99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in nontransfused (n = 1138) and transfused (n = 895) men, 1.0% versus 1.7% (p = 0.16). HLA antibodies were detected in 17.3% of all female donors (n = 5834) and in 24.4% of those with a history of previous pregnancy (n = 3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7% (zero), 11.2% (one), 22.5% (two), 27.5% (three), and 32.2% (four or more pregnancies; p < 0.0001). HLA Class I and Class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk reduction measure.

The impact of discontinuation of 7‐day storage of apheresis platelets (PASSPORT) on recipient safety: an illustration of the need for proper risk assessments

Seven-day stored apheresis platelets (APs) were withdrawn from the US market after detection of two culture-positive units from 2571 tested at outdate in the PASSPORT surveillance study. The impact of this discontinuation on recipient safety was explored using mathematical modeling. Risk models for septic transfusion reactions (STRs) and transfusion-related acute lung injury (TRALI) were developed. Key assumptions were 400,000 annual APs transfused, equivalent STR risk for platelets (PLTs) stored for 5 days or more and zero for PLTs stored for less than 5 days, whole blood-derived PLTs (WBplts) administered in 5-unit pools, a 4.6-fold higher risk of false-negatives with surrogate versus culture-based bacterial testing, an AP TRALI risk between 1 per 1000 and 1 per 10,000, and a delay in TRALI risk reduction implementation in some centers by 6 to 12 months due to limited PLT availability. STR risk could increase, decrease, or remain the same depending on the percentage of inventory replaced by surrogate-tested WBplts versus culture-tested apheresis or whole blood PLTs. A delay in TRALI risk reduction implementation is likely to result in a comparable or greater risk during the delayed implementation period than the safety achieved with regard to STRs, even in the most favorable case scenario. A comprehensive risk assessment should have been conducted before the decision to discontinue PASSPORT. Risk assessments using accepted methods (and actual data when available) should precede any major blood safety decisions.