Nonleukoreduced Blood Research Articles

Leukoreduction as a control measure in transfusion transmission of visceral leishmaniasis.

Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood-borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission. A total of 161 polytransfused patients with non-leukoreduced blood components (HNL), 95 polytransfused with leukoreduced blood components (LH), and 202 non-transfused (NT) from endemic regions for VL and with a similar epidemiological profile. The detection of antibodies against VL was performed by ELISA and the presence of the parasite was investigated by real-time PCR. Statistical significance was defined as p < .05. When comparing three groups, ELISA results were statistically significant (p=.0065). The residual analysis of ELISA showed statistically significant for the HNL group compared to the general group (p=.002; OR: 5.6; CI: 1.7-25.8), demonstrating that individuals who received non-leukoreduced transfusions are five times more likely to acquire Leishmania infantum infection than the general. Higher prevalence in the group with HNL and low prevalence in those who received LH, similar to NT patients, highlight the risk of transfusional VL transmission and reinforce the role of leukoreduction in its prevention.

Are we missing reverse TRALI? – A real world experience from a tertiary care oncology centre in India

Transfusion related acute lung injury (TRALI) is a rare but potentially fatal pulmonary complication of transfusion that presents as acute hypoxemia and non-cardiogenic pulmonary oedema, developing during or within six hours of transfusion. Majority of the cases reported are due to transfusion of plasma rich blood components containing antibodies to human leukocyte antigen (anti-HLA) or human neutrophil antigen (anti-HNA). Rarely, anti-HLA or anti-HNA in recipients against transfused donor leukocyte antigens, cause TRALI by a reverse mechanism. Herein, we report three cases of suspected TRALI following transfusions of buffy coat derived granulocytes and peripheral blood stem cells. Three patients with hematological malignancies developed pulmonary symptoms after transfusions of leukocyte rich blood components. All cases showed findings of bilateral pulmonary infiltrates at chest radiography and patients were managed accordingly; however, all three expired within seven days of transfusion due to progressive respiratory deterioration. The patients were transfusion dependent for a long time and had received multiple non-leukoreduced blood components in the past. Clinical findings in all three cases indicate the possibility of reverse TRALI. Although, patients’ anti-HLA or anti-HNA antibodies concordance with donors’ cognate antigens (HLA and HNA) was not confirmed; yet these three cases suggest that reverse pathogenesis of TRALI is not as infrequent as reported in the literature. However, reverse TRALI has not been confirmed as the presence and nature of antibodies in the transfused recipient were not investigated due to the non availability of immunodiagnostic tests in India.

Spectrum of alloimmunization among multitransfused beta-thalassemia major patients

Introduction: The development of alloantibodies is a major problem among thalassemia major individuals due to periodic blood transfusions. The current study assessed the frequency and specificity of erythrocytes alloimmunization and also the variables affecting the extent of alloimmunization in repeatedly transfused thalassemia patients. Materials and Methods: This prospective, cross-sectional study was conducted at the Department of Blood Transfusion Services and Thalassemia Centre of Pakistan Institute of Medical Sciences from August 2017 to February 2018. Of the 475 thalassemia major patients, alloantibodies were screened and identified by 3-red cell antigen panel and afterward by an extended 11-cell antigen panel. The data analysis was done through SPSS version 20.0. Chi-square test was employed. Results: Alloantibodies were detected in 77 (16.2%) patients, 5 (6.5%) patients were found with double alloantibodies. Anti-D (31.1%) and Anti-E (29.9%) antibodies had the highest incidence and were found in 24 and 23 patients, independently. Anti-K antibody was observed in 11 (14.3%) and Anti-C in 3 (3.9%) patients. Anti-C (2.6%), Anti-E (2.6%), and Anti-Kpa (2.6%) all were found in two patients, individually. Similarly, Cw (1.3%), k (1.3%), Jka (1.3%), Anti-Fyb (1.3%), and Anti-s (1.3%) antibodies were detected in one patient each. Alloantibodies were common in males, splenectomized patients, in those who initiated their transfusions before 2 years of age, in patients receiving nonleukoreduced blood and in B and O blood group patients. Conclusion: The proper management and prudence are needed for thalassemia patients due to hemolytic nature of these alloantibodies. New techniques should be introduced to reduce the incidence of red blood cell alloimmunization.

Tracking Syngeneic Leukocytes after Transfusion of Non-leukoreduced Blood in a Murine Model

Objective: Several Western European countries and Canada have introduced white blood cell reduction as a universal standard to prevent potential adverse effects of allogeneic blood transfusions. However, there is an ongoing controversy regarding its appropriateness in other countries such as North America. We were interested in the whereabouts of leukocytes following whole blood transfusion in mice to evaluate their potential sites of (adverse) action. Materials and methods: Wildtype C57BL/6 were transfused with non-leukoreduced blood from enhanced green fluorescent protein transgenic C57BL/6-Tg(CAGEGFP) 1 Osb/J mice. Cells were tracked on day 3 and day 5 after transfusion by flow cytometry. Results: Enhanced green fluorescent protein-labeled leukocytes were found in the blood circulation, the myocardium, bone marrow and lung tissue up until day 5, but not in the kidney, the liver or the spleen. Myeloperoxidase activity in the lungs was significantly higher on day 5 when compared to control animals (0.09 ± 0.01% vs. 0.26 ± 0.08%, p=0.047). There was no increase in cytokines. Conclusion: Syngeneic white blood cells survive in the recipient of non-leukoreduced red blood cell units. They circulate in the blood stream and can be found in the bone marrow and the lungs up to five days after transfusion.

Natural Antioxidants Improve Red Blood Cell “Survival” in Non-Leukoreduced Blood Samples

Background: Blood collected in an anticoagulant can be kept refrigerated in an unmodified state within 5 - 6 weeks. Oxidative damage is considered to be a one of the major factors contributing to the development of storage lesions. Lipid and membrane proteins oxidation results in changes in cation gradients that affect the cell survival. Aim: In the present study we used the natural antioxidants and ion channels blockers (L-carnosine, spermine, phloretin and their mixtures) to prolong “survival” of red blood cells (RBCs), measured as the lack of PS exposure and cell hemolysis, in the Alsever's preservative solution upon hypothermic storage. Results: We show that the mixture of carnosine (20 mM), spermine (20 µM) and phloretin (100 µM) effectively blunted phosphatidylserine (PS) exposure, Ca²⁺ accumulation and RBCs hemolysis in non-leukoreduced low (∼2%) hematocrit samples after 36 days of storage as well as after 1 day of post-storage incubation of the stored cells in physiological saline solution. In addition, a slight but significant decrease in PS exposure was observed in non-leukoreduced high (∼20%) hematocrit samples after 36 days of storage with the mixture of substances. Conclusion: We conclude that the use of the mixture of natural antioxidants (carnosine, spermine, and phloretin) as an additive to blood preservative solution provides better RBCs storage and “survival”.

Perioperative allogeneic nonleukoreduced blood transfusion and prostate cancer outcomes after radical prostatectomy

Allogeneic blood transfusion induces immunosuppression, and concern has been raised that it may increase propensity for cancer recurrence; however, these effects have not been confirmed. We examined the association of perioperative transfusion of allogeneic blood long-term oncologic outcomes in patients with prostate cancer who underwent prostatectomy. We reviewed medical records of patients who underwent radical prostatectomy between 1991 and 2005 and received allogeneic nonleukoreduced blood. Each transfused patient was matched to two controls who did not receive blood: matching included age, surgical year, prostate-specific antigen level, pathologic tumor stages, pathologic Gleason scores, and anesthetic type. Primary outcome was systemic tumor progression, with secondary outcomes of prostate cancer death and all-cause mortality. Stratified proportional hazards regression analysis was used to assess differences in outcomes between the transfused and nontransfused group. A total of 379 prostatectomy patients who were transfused and 758 nontransfused controls were followed for 9.4 and 10.2 years (median), respectively. In a multivariable analysis that took into account the matched study design and adjusted for positive surgical margins and adjuvant therapies, the use of allogeneic blood was not associated with systemic tumor progression (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.39-1.99; p = 0.76), prostate cancer-specific death (HR, 1.69; 95% CI, 0.44 to 6.48; p = 0.44), or all-cause death (HR, 1.20; 95% CI, 0.87 to 1.67; p = 0.27). When adjusted for clinicopathologic and procedural variables transfusion of allogeneic blood was not associated with systemic tumor progression and survival outcomes.

Leukoreduction and ultraviolet treatment reduce both the magnitude and the duration of the HLA antibody response

Both leukoreduction and ultraviolet (UV) light treatment of blood products have been shown to reduce the incidence of HLA antibody development in recipients, but the impact of these treatments on the magnitude and persistence of the antibody response is less clear. Longitudinal samples from 319 subjects taken from four different study cohorts were evaluated for HLA antibodies to determine the effects of leukoreduction and UV treatment on HLA antibody generation and persistence. Subjects receiving leukoreduced or UV-treated blood products were less likely to generate Class I HLA antibodies, and those receiving leukoreduced blood were also less likely to generate Class II HLA antibodies. Among those receiving nonleukoreduced blood, 55% developed Class I HLA antibodies and 51% developed Class II HLA antibodies compared with 28% (Class I) and 15% (Class II) for those receiving leukoreduced blood and 36% (Class I) and 54% (Class II) for those receiving UV-treated blood. Among alloimmunized subjects, leukoreduction resulted in a significant twofold reduction in the magnitude of Class I HLA antibodies, and UV treatment resulted in a significant threefold reduction in the magnitude of Class II HLA antibodies. Both treatments resulted in shorter persistence of Class I HLA antibodies. These data demonstrate that leukoreduction and UV treatment of blood products results not only in a reduction in the incidence of HLA antibody production, but also in lower and more transient HLA antibody levels among sensitized transfusion recipients.

The reintroduction of nonleukoreduced blood: would patients and clinicians agree?

With today’s economic uncertainty, hospitals continue to look for new ways to reduce costs in a safe fashion. Some hospitals currently providing only leukoreduced blood have considered providing nonleukoreduced blood components for their patients, presumably assuming that nonleukoreduced blood is less expensive than leukoreduced blood. This commentary examines the safety of the reintroduction of nonleukoreduced blood components in hospitals that previously implemented universal leukoreduction. Because universal leukoreduction has been in place in most hospitals for almost a decade, 1 many clinicians have never had to weigh the risks and benefits of leukoreduced and nonleukoreduced products, and currently they are not required to decide whether nonleukoreduced components would be seriously detrimental for their patients. In the past there was debate about whether universal leukoreduction was cost-effective, but the debate did not include a balancing of risks and benefits, because no true risks have been identified (aside from device failures). 2-7

Prognosticators in thigh soft tissue sarcomas

In sarcoma patients the roles of smoking history, family cancer history, and leukoreduced blood transfusions have not been studied and the effect of preoperative radiation on blood loss has not been examined. Seventy-seven patients with non-metastatic and non-recurrent thigh sarcomas surgically treated at the Cleveland Clinic were identified. Among patient variables studied were: close family history of cancer, perioperative transfusion history, smoking history, and radiation history. Median follow-up for the survivors was 3.2 years. We found that tumor grade, transfusion >3 U (P = 0.022), and pre- or post-operative radiation therapy (P = 0.041) were risk factors for distant metastasis. Tumor grade (P = 0.008), positive smoking history (P = 0.039), and >3 U of non-leukoreduced blood transfused (P = 0.037) were risk factors for death of any-cause. Close family history of cancer correlated with having a grade 3 sarcoma (P = 0.044). Neoadjuvant radiotherapy correlated with >3 U of blood transfused (P = 0.001) and biopsy performed at the treating institution led to a significant decrease in rate of recurrence (P = 0.016). We present novel findings in terms of transfusions, family history of cancer and site of initial biopsy in sarcoma patients.

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion

Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.

Use of Leukoreduced Blood Does Not Reduce Infection, Organ Failure, or Mortality Following Trauma

BackgroundLeukoreduced (LR) blood has been demonstrated to reduce morbidity and mortality in high-risk surgical patients, but not in trauma patients. The objective of the present study was to determine the effect of LR blood on morbidity and mortality. We hypothesized that the use of LR blood does not improve outcome in trauma patients.MethodsThis study was a retrospective cohort analysis of trauma patients transfused at a level 1 Trauma Center from 2001 to 2004. Between 2002 and 2003, LR blood was transfused. Prior to that time and subsequent to it, non-leukoreduced (NLR) blood was transfused. This created two historical comparison groups. Data collected included patient demographics, units of blood transfused, intensive care unit (ICU) and hospital days, ventilator days, injury severity score (ISS), mortality, presence of acute respiratory distress syndrome (ARDS), and infectious complications. A multiple organ dysfunction syndrome (MODS) score was calculated.ResultsThe distribution of patients was as follows: 284 patients received only NLR blood, 153 received only LR blood, and 58 received at least one unit of each. The mean ISS was similar (NLR: 26, LR: 24; P > 0.1). No differences were seen between groups in units transfused (6.2 vs. 5.5), number of ICU days (8.2 vs. 9.0), number of hospital days (16.9 vs. 18.6), number of ventilator days (6.1 vs. 5.7), incidence of ARDS (8.3% vs. 8.5%), MODS score (5.5 vs. 5.9), mortality rate (15.1% vs. 15.7%), or infection rate (36% vs. 30%) (P > 0.1).ConclusionsThis study represents the largest series comparing trauma patients who received either LR or standard blood transfusions. The use of LR blood does not improve outcome in trauma patients.

Effect of Storage on Levels of Nitric Oxide Derivatives in Blood Components

In light of recent papers stressing the importance of decreased levels of SNO-hemoglobin (SNO-Hb) to the pronounced nature of deleterious effects of transfusion of stored red blood cells (RBCs), there has been an increased interest in the practice of blood storage. Dejam et al. (Blood, 2005) previously demonstrated the critical nature of RBCs in NO physiology: they serve as the major intravascular stores of nitrite, which is eventually converted to NO, an important player in vasoregulation. The purpose of this study is to quantify the NO metabolites, nitrite and nitrate, in three blood components and evaluate their levels over time of storage. Blood obtained from 6 healthy volunteer donors was split into whole blood, leukoreduced, and non-leukoreduced packed RBCs and stored in polyvinyl chloride (PVC) bags for 42 days at 4°C. PVC bags were maintained in either room air or an argon chamber. Nitrite, nitrate, and SNO-Hb/nitrosyl-hemoglobin (HbNO) were measured using reductive gas-phase chemiluminescence. In all blood components, the nitrite and nitrate were detected in higher concentrations in RBCs than in the extracellular fluid compartment. Mean nitrite value immediately before storage was 152±13nM, but fell rapidly upon storage. Nitrite levels continued to decrease with storage time, while nitrate levels remained constant for the duration of storage. In the leukoreduced blood product, nitrite levels were 75±8nM on day 1 and 50±9nM by day 42; the concentration of nitrate in the leukoreduced blood product was 34±3uM on day 1 and 34±4uM on day 42. The nitrite levels in non-leukoreduced blood product were 76±12nM on day 1 and 37±7 by day 42; the nitrate concentration in the non-leukoreduced blood product was 35±3uM on day 1 and 32±0.4uM on day 42. In whole blood, nitrite levels were 64±11nM on day 1 and 44±9nM by day 42; the nitrate concentration was 47±2uM on day 1 and 43±6uM on day 42. SNO-Hb levels were very low in fresh blood and virtually undetectable after one day of storage. Interestingly, nitrite levels never reached zero. Enzyme inhibitors—L-NAME (nitric oxide synthase inhibitor), acetazolamide (carbonic anhydrase inhibitor), and oxypurinol (xanthine oxidase inhibitor)—did not lower nitrite levels enough to explain the remaining nitrite present in the PVC bags after 42 days. pH decreased slightly, while pO2 increased in all three components during storage; this is likely due to the diffusion of oxygen from room air into the PVC bags. Control experiments with saline showed an increase in nitrite levels, while nitrate levels remained stable over 42 days. When stored in an argon chamber, both blood and saline samples showed relatively lower nitrite levels than their room air counterparts. Thus, during blood bank storage, nitrite levels decrease in blood while nitrate levels remain stable. The diffusion of nitrogenous gases may explain why nitrite does not completely disappear under standard storage conditions. Our results suggest that most of the NO pathway is initially retained, but greater changes occur with prolonged storage. These measurements of NO derivatives may have implications for transfusion therapy, explaining some of the adverse effects seen with RBC transfusion and providing a foundation for enhancing blood preservation through improvement of storage practices.

Immunomodulatory effects of blood transfusions: the synergic role of soluble HLA Class I free heavy‐chain molecules detectable in blood components

Over the past decades, the weight of the published literature demonstrates that blood transfusions can induce clinically significant immunosuppression in recipients. Several studies showed significant improved clinical outcomes in the patients receiving leukoreduced transfusions, compared with control patients who received nonleukoreduced transfusions. Moreover, the immunosuppressive potential of blood products grows with the time of their storage and becomes highest in nonleukoreduced blood products stored for a long time. The interest was previously focused on the determination of immunomodulatory soluble molecules such as soluble HLA Class I (sHLA-I) and soluble Fas ligand (sFasL) in different blood components and on the evaluation of their immunomodulatory activities. On this basis, whether soluble beta2-microglobulin free HLA Class I heavy chains (sHLA-beta2fHC) could be detected and immunochemically characterized in different blood components was evaluated. Immunomodulatory activity of detectable sHLA-beta2fHC molecules was evaluated by apoptosis inducing capacity in interleukin-2-activated antigen-specific cytotoxic T lymphocytes (CTL). Double-determinant immunoenzymatic assay indicates that sHLA-beta2fHC levels in red blood cells stored for up to 30 days and in random-donor platelets are significantly (p < 0.001) higher than in other blood components, and the immunochemical characterization suggests that the major source of sHLA-beta2fHC molecules might be the residual white cells that undergo membrane damage during storage. Finally, allogeneic CD8+ CTL apoptosis induction confirmed biofunctionality of sHLA-beta2fHC molecules. These data are comparable with those previously reported dealing with contaminant soluble molecules in allogeneic and autologous blood components, suggesting that sHLA-beta2fHC molecules could contribute to the immunosuppressive effects of blood transfusions.

Safety procedures of coagulation factors

Two main types of safety procedures must be applied to biological products, including plasma derivatives: (i) preventive procedures and (ii) elimination procedures.Prevention includes epidemiological control of donor populations; checks on each donor’s health condition; analysis of each donation for the main pathogens using serological methods; additional analysis of all plasma for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis A virus (HAV) and the B19 virus, using nucleic acid amplification techniques (NAT). A 60 days or longer inventory hold of all plasma donations is applied, to allow additional time to discard previous donations from potential seroconverting or otherwise rejectable donors.Elimination procedures minimize the low residual risk of transmitting pathogens, including unknown or previously undetected ones. Since the introduction 20 years ago of solvent‐detergent treatment, very effective against enveloped viruses (HIV, HBV, HCV, West Nile virus, SARS, avian influenza virus etc), there have been no known cases of transmission of this type of pathogens by products manufactured according to this procedure. Other inactivation procedures such as pasteurization, dry‐heat or nanofiltration may prove equally effective. In addition, dry‐heat treatment and nanofiltration are capable of effectively eliminating non‐enveloped viruses (HAV, B19 virus). Recent studies show that the B19 virus is much more sensitive to heat (in lyophilized state or by pasteurization) and acid pH than previously thought.Although there is no evidence for the transmission of classic transmissible spongiform encephalopathies (TSEs) through blood or blood‐products transfusion, four possible cases have been reported in the United Kingdom involving transmission by non‐leukoreduced blood components of the agent that causes variant Creutzfeldt‐Jakob Disease (vCJD), a disease linked to the outbreak of bovine spongiform encephalopathy (BSE) which took place in that country. However, there are no cases of human TSE (classic or variant) transmission by plasma‐derived products. Analytical methods capable of detecting the vCJD agent in patients’ brains (where high titres are found) and other tissues (such as the spleen, appendix and lymph nodes, where much lower concentrations are found) are unable to detect the agent in blood or plasma from patients with vCJD, even in the clinical phase of the disease. Experiments by Grifols and other groups show that the capacity of the production processes to eliminate vCJD agent models is many orders of magnitude greater than the maximum expected load of the agent. In this regard, the efficacy of precipitation, affinity chromatography, depth filtration and nanofiltration are particularly notable.

Increased Risk of Infection and Mortality in Women after Cardiac Surgery Related to Allogeneic Blood Transfusion

Infection and mortality rates are greater in women than in men after cardiac surgery. This study was conducted to assess whether allogeneic blood transfusion could partially account for this gender difference, as transfusion has been associated with immunomodulation. A cohort study was conducted in 380 patients at the University of Rochester Medical Center. Subjects were adult patients who underwent primary coronary artery bypass graft (CABG) surgery, primary valve replacement surgery, or both. Information was collected about blood components transfused, as well as postoperative infection, pulmonary dysfunction, and in-hospital mortality. Women were more likely to receive allogeneic red blood cells (RBCs) or platelets than men (odds ratio [OR] 21.6, 95% CI 3.8, 124.2) and a greater quantity of blood than men. Patients who received allogeneic blood were 4.4 times more likely to develop an infection than those who did not (95% CI 1.5, 13.2). There was a positive linear correlation between number of units of blood received and number of days with fever (p<0.001) and hospital length of stay (p<0.001). This was particularly evident in patients who received four or more units of nonleukoreduced blood components. Women had a greater risk of infection (p=0.005), pulmonary dysfunction (p=0.005), and mortality (p=0.007) than men during hospitalization. One reason for the greater mortality in women after cardiac surgery may be the increased likelihood of receiving nonleukoreduced allogeneic RBCs and platelets. Transfusion increased the risk of infection; infection, then, increased the likelihood of pulmonary dysfunction and mortality.

Microchimerism: a lasting legacy of transfusion?

Microchimerism: a lasting legacy of transfusion?

Leukoreduction of blood transfusions does not diminish transfusion‐associated microchimerism in trauma patients

Transfusion of trauma patients can result in long-term survival of donor white blood cells (WBCs) or "transfusion-associated microchimerism" (TA-MC). The aim was to determine whether leukoreduction of blood transfusions, advocated to reduce the immunomodulatory effect of transfusion, decreases the likelihood of developing TA-MC. A subgroup of trauma patients from a randomized trial was examined, evaluating the risk of infection following leukoreduced versus nonleukoreduced blood transfusion. Patients' blood was sampled at least 1 month after hospital discharge, and TA-MC was assessed with quantitative allele-specific polymerase chain reaction detection of differences at the HLA-DR locus or a panel of insertion-deletion polymorphism loci distributed throughout the chromosomal complement. At the time of blood sampling, a scripted interview was used to ascertain symptoms suggestive of chronic graft-versus host disease (cGVHD). For 67 patients evaluated, the mean age was 43 +/- 17 years and mean Injury Severity Score was 24 +/- 12. Median time from injury to blood sampling for TA-MC was 240 (interquartile range, 116-360) days. Nine of 32 patients (28%) in the nonleukoreduced transfusion group developed TA-MC compared to 13 of 35 patients (37%) in the leukoreduced group (p = 0.43). Subjects with TA-MC were no more likely than subjects without TA-MC to have at least one symptom suggestive of cGVHD (64% vs. 76%, respectively). TA-MC seems to be a prevalent condition among injured patients at the second of two regional trauma centers evaluated, suggesting that it is a common phenomenon after transfusion in the setting of injury. Although leukoreduction removes greater than 99.9 percent of donor WBCs, it fails to prevent or even substantially reduce the likelihood of developing TA-MC. TA-MC does not appear to be strongly associated with symptoms suggestive of cGVHD several months after transfusion.

Clinical effects of reverting from leukoreduced to nonleukoreduced blood in cardiac surgery

A reduction in postoperative length of stay (PLOS) was recently demonstrated with the use of leukoreduced (LR) blood in cardiac surgery patients compared to a historical cohort who received non-LR blood. Follow-up data are now presented in a similar population after a 12-month period in which LR blood was no longer routinely used. This is an extension of a study in which all patients admitted over a 12-month period for open heart surgery were given LR blood (Group 2) and were compared against a historical cohort given non-LR blood (Group 1). This study measures the outcomes of a new cohort of patients admitted during a 12-month period where LR blood was no longer routinely used (Group 3). PLOS increased in patients who received transfusions with non-LR blood (Group 3, n = 595) versus patients with LR blood (Group 2, n = 645; p = 0.045 by nonparametric rank U test). Mean PLOS increased from 9.5 days (95% confidence interval [CI], 8.9-10.0) to 10.8 days (95% CI, 10.0-11.6). In comparison, an earlier cohort who received non-LR blood (Group 1, n = 501) had a mean PLOS of 10.1 days (95% CI, 9.4-10.7). With the exception of decreased red blood cell (RBC) usage in Group 3, there were no significant differences in non-RBC blood usage, estimated blood loss, bypass time, mediastinitis rates, operative mortality rate, or overall mix of cases. The use of non-LR blood for cardiac surgery was associated with an increased PLOS compared to the use of LR blood and supports our previous demonstration of the benefits of LR blood in cardiac surgery.

Prestorage leukoreduction moderates transfusion-induced pancreatic cancer progression in a murine model

INTRODUCTION: White blood cells (WBCs) and platelets in packed red blood cells (pRBCs) release immunomodulating substances during storage, which may be decreased by pre-storage leukoreduction (PSL). Clinical studies in cancer patients have not demonstrated a benefit of PSL. We hypothesize intravenous (IV) administration of plasma from non-leukoreduced (NLR) vs. leukoreduced (LR) blood will cause differential pancreatic tumor progression in mice. METHODS: Acellular plasma was removed from both LR and NLR aliquots of a single unit of human pRBCs at day 1 (D.1) and day 42 (D.42) of storage. Mice with established pancreatic tumors underwent a sham operation along with IV injection of D.1 LR/NLR, D.42 LR/NLR plasma, or saline. Mice were sacrificed 14 days later.

High‐level long‐term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury

Long-term white blood cell (WBC) microchimerism (MC), of at least 2 years, has been reported in trauma patients receiving fresh nonleukoreduced (non-LR) blood. It is unknown, however, whether this occurs with LR blood products that are nearly devoid of WBCs. Twenty-seven patients transfused with LR and non-LR blood products were studied after severe traumatic injury. A secondary aim was to explore donor-recipient mixed lymphocyte reactivity in vitro. To quantify MC, allele-specific real-time polymerase chain reaction assays were developed targeting HLA Class II sequence polymorphisms. Extensive validation showed that these assays reliably detect a single copy of target sequence in a complex allogeneic background without false positivity. At a median follow-up of 26 months (range, 24-39 months), long-term MC was observed in 3 of 20 patients (15%) who received non-LR blood products and 2 of 7 (29%) who received LR blood products. The maximum MC ranged from 0.40 to 4.90 percent of circulating WBCs and appeared, by Class II genotype analysis, to be attributable to a single donor. It is concluded that robust levels of long-term MC, apparently traceable to a single donor, occur at similar frequency despite leukoreduction of transfused blood products. Exploratory analysis of donor-recipient mixed lymphocyte reactivity suggests that long-term MC may require a state of bidirectional tolerance before transfusion.