The continuing risk of transfusion-transmitted infections.
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Bacterial Infections↗
Biomedical subjects
Morris A Blajchman
Publications and source records attributed to Morris A Blajchman.
The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants.
OBJECTIVE: To determine whether extremely low birth weight infants (ELBW) transfused at lower hemoglobin thresholds versus higher thresholds have different rates of survival or morbidity at discharge. STUDY DESIGN: Infants weighing <1000 g birth weight were randomly assigned within 48 hours of birth to a transfusion algorithm of either low or high hemoglobin transfusion thresholds. The composite primary outcome was death before home discharge or survival with any of either severe retinopathy, bronchopulmonary dysplasia, or brain injury on cranial ultrasound. Morbidity outcomes were assessed, blinded to allocation. RESULTS: Four hundred fifty-one infants were randomly assigned to low (n = 223) or high (n = 228) hemoglobin thresholds. Groups were similar, with mean birth weight of 770 g and gestational age of 26 weeks. Fewer infants received one or more transfusions in the low threshold group (89% low versus 95% high, P = .037). Rates of the primary outcome were 74.0% in the low threshold group and 69.7% in the high (P = .25; risk difference, 2.7%; 95% CI -3.7% to 9.2%). There were no statistically significant differences between groups in any secondary outcome. CONCLUSIONS: In extremely low birth weight infants, maintaining a higher hemoglobin level results in more infants receiving transfusions but confers little evidence of benefit.
Algorithms↗
Randomized trials in patients with blunt and penetrating trauma.
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Drug Industry↗
In vivo recovery and survival of apheresis and whole blood-derived platelets: a paired comparison in healthy volunteers.
BACKGROUND: Methods of platelet preparation may alter the recovery and survival characteristics of platelets following transfusion. As suggested by a recent clinical trial, platelet recovery may be better preserved with apheresis platelet preparations than with platelets prepared from whole blood by the platelet-rich plasma (PRP) method. STUDY DESIGN AND METHODS: In vivo platelet recovery and survival of autologous leukoreduced (LR) apheresis platelets and autologous filter-LR PRP platelets were compared in 22 healthy volunteers using a paired crossover design. On the same day, each participant gave one apheresis platelet donation and one whole blood donation from which platelets were recovered from the PRP. The sequence of donations was randomly assigned for each participant. Following 5 days of storage and bacterial screening, a sample from each platelet product was labeled with either (51)chromium or (111)indium (randomly assigned) and both samples were simultaneously re-infused into the original donor. Recovery and gamma-function platelet survival were calculated for each platelet product using the multiple hit mathematical model. RESULTS: Five day stored LR-apheresis platelets had 18.8 percent better recovery, and 32.9 percent longer gamma-survival than filter-LR PRP platelets. Stored apheresis platelets had lower p-selectin expression and higher morphology scores than stored PRP platelets. CONCLUSIONS: Filter-LR PRP platelet preparation appears to adversely affect platelet recovery and survival characteristics. The reasons for this effect are not clear. These results may not apply to all apheresis and PRP methods of platelet preparation.
Adult↗
Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin.
Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk = 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.
Aprotinin↗
Research ethics boards: the protection of human subjects.
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Canada↗
Proceedings of a consensus conference: towards an understanding of TRALI.
Transfusion-related acute lung injury is a relatively uncommon transfusion-associated adverse effect occurring during or soon after an allogeneic blood transfusion. Transfusion-related acute lung injury is a complex syndrome that has many manifestations and has only recently been identified to be an important cause of transfusion-associated morbidity and mortality. But despite its increasing recognition, much about the pathogenesis, treatment, and prevention is poorly understood and often controversial. The purpose of this consensus conference was to bring together international experts in an effort to try to standardize a case definition, which could be used to enhance future understanding of transfusion-related acute lung injury including its epidemiology, pathogenesis, management, prevention, and research. These proceedings are being provided with a view to making available to the transfusion medicine community the considerable amount of important information presented at this consensus conference by the invited international panel of experts.
Adult↗
Protecting the blood supply from emerging pathogens: the role of pathogen inactivation.
Although the risk of infection by blood transfusion is relatively low, breakthrough infections still occur, Transfusion-related fatalities caused by infections continue to be reported, and blood is not tested for many potentially dangerous pathogens. The current paradigm for increasing the safety of the blood supply is the development and implementation of laboratory screening methods and restrictive donor criteria. When considering the large number of known pathogens and the fact that pathogens continue to emerge, it is clear that the utility of new tests and donor restrictions will continue to be a challenge when considering the cost of developing and implementing new screening assays, the loss of potential donors, and the risk of testing errors. Despite improving the safety of blood components, testing remains a reactive approach to blood safety. The contaminating organisms must be identified before sensitive tests can be developed. In contrast, pathogen inactivation is a proactive strategy designed to inactivate a pathogen before it enters the blood supply. Almost all pathogen inactivation technologies target nucleic acids, allowing for the inactivation of a variety of nucleic acid-containing pathogens within plasma, platelets, or red blood cells thus providing the potential to reduce transfusion-transmitted diseases. However, widespread use of a pathogen inactivation technology can only be realized when proven safe and efficacious and not cost-prohibitive.
Anti-Infective Agents↗
Bacterial detection of platelets: current problems and possible resolutions.
The greatest transfusion-transmitted disease risk facing a transfusion recipient is that of bacterial sepsis. The prevalence of bacterial contamination in platelets and red blood cells is approximately 1 in 3,000 units transfused. The available data indicate that transfusion-associated sepsis develops after 1 in 25,000 platelet transfusions and 1 in 250,000 red blood cell transfusions. One of the most widely used strategies for decreasing bacterial sepsis risk is bacterial detection. A roundtable meeting of experts was convened during the XXVIII Annual Congress of the International Society of Blood Transfusion (Edinburgh, UK, July 2004) to provide a forum for experts to share their experiences in the routine bacterial detection of platelet products. This article summarizes the presentations, discussions, and recommendations of the panel. The data presented indicate that some of the current bacterial screening technology is useful for blocking the issuance of platelet units that contain relatively high levels of contaminating bacteria. Platelet units are usually released based on a test-negative status, which often become test-positive only upon longer storage. These data thus suggest that bacterial screening may not prevent all transfusion-transmitted bacterial infections. Two transfusion-transmitted case reports further highlighted the limitation of the routine bacterial screening of platelet products. It was felt that newer technologies, such as pathogen inactivation, may represent a more reliable process, with a higher level of safety. The panel thus recommended that the Transfusion Medicine community may need to change its thinking (paradigm) about bacterial detection, toward the possibility of the pathogen inactivation of blood products, to deal with the bacterial contamination issue. It was suggested, where permitted by regulatory agencies, that blood centers should consider adopting first-generation pathogen inactivation systems as a more effective approach to reducing the risk of transfusion-associated sepsis than some of the approaches currently available.
Bacteria↗
Transfusion-related acute lung injury.
PURPOSE OF REVIEW: Transfusion-related acute lung injury is an uncommon complication of blood transfusion typically manifested by shortness of breath, fever, and hypotension. Transfusion-related acute lung injury is an important cause of transfusion-related morbidity and mortality. RECENT FINDINGS: Much about the pathogenesis, treatment, and prevention of transfusion-related acute lung injury is poorly understood or is controversial. There is increasing recognition that transfusion-related acute lung injury is an important clinical syndrome, causing most transfusion-related deaths. SUMMARY: In this report, what is known about transfusion-related acute lung injury is summarized with particular emphasis on recent studies. Some of the areas in which knowledge and/or consensus are currently lacking are identified.
Humans↗
Landmark studies that have changed the practice of transfusion medicine.
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Blood Transfusion↗
Fibrinogen catabolism within the procoagulant VX-2 tumor of rabbit lung in vivo: Effluxing fibrin(ogen) fragments contain antiangiogenic activity.
Many types of solid tumors are known to be procoagulant environments. This is partly because a hyperpermeable vascular system within the tumor allows plasma hemostatic factors to accumulate in relatively high concentrations in the stroma, and many solid-tumor cells express tissue factor or a procoagulant factor. These circumstances appear to exist in the VX-2 lung tumor of the New Zealand White (NZW) rabbit, and they sustain a measurable turnover of stromal deposits of fibrin(ogen). We have measured the turnover of fibrinogen within tumors of the VX-2 tumor-burdened rabbit and analysed the catabolic products of fibrin(ogen) and the status of fibrinolysis in tumor-derived interpleural effusate. Using intravenously injected (125)I-labeled rabbit fibrinogen as a marker, we found that fibrinogen (approximate blood concentration 1740 microg/mL) passed from blood to VX-2 tumor stroma, saturating the tumor at a concentration of approximately 348 microg fibrinogen/g in approximately 12 hours. We measured fibrin(ogen) fragments, at a concentration of approximately 292 microg/mL, in interpleural effusates that we recovered from 13% of the VX-2-burdened rabbits. Unreduced fibrin(ogen) fragments consisted of 4 major components with a relative molecular mass of approximately 250,000 (assumed to be fragment X; approximately 9% of total fragments from densitometry of immunoblots), 200,000 (d-dimer; 41%), 110,000 (fragment D; 49%), and 50,000 to 55,000 (fragment E; 1%-2%) kD. Total fibrin(ogen) fragments immunopurified from effusates exhibited an antiangiogenic effect when subjected to a chick embryo chorioallantoic membrane procedure. Interpleural effusates were devoid of plasmin activity or active plasminogen activator inhibitor-1 but contained plasmin complexes and active urokinase-like plasminogen activator (uPA), alpha(2)-antiplasmin, and thrombin-activatable fibrinolysis inhibitor. We speculate that VX-2 cells release uPA to activate fibrinolysis within the tumor stroma. Catabolic products of hemostasis (eg, fibrinolytic fragments, angiostatin) flux from the stroma into the interpleural space, thereby providing a net antiangiogenic property to the effusate and ultimately to the lymphatic and circulatory systems.
Animals↗
Improving the bacteriological safety of platelet transfusions.
Despite the increased application of aseptic techniques for blood collection and the preparation of platelet concentrates, morbidity and mortality arising from the transfusion of bacterially contaminated allogeneic platelet products persist. This problem exists because stored platelet concentrates represent a nearly ideal growth medium for bacteria and because they are stored at temperatures (22 degrees +/- 2 degrees C) that facilitate bacterial growth. The presence of bacteria in blood components including platelets has been a problem for many decades and currently is the most common microbiological cause of transfusion-associated morbidity and mortality. A variety of strategies have been devised and/or proposed in an attempt to try to reduce the risk of transfusion-associated sepsis. These include pretransfusion bacterial detection, efforts to reduce the likelihood of bacterial contamination, the optimization of blood product processing and storage, reducing recipient exposure, and the introduction of pathogen inactivation methodology. With regard to doing bacterial detection, a number of automated detection systems have become available to test for contaminated platelet components, but their utility to some extent is restricted by the time they take to indicate the presence of bacteria and/or their lack of sensitivity to detect initially low bacterial loads. A variety of other approaches has been shown to reduce the risk of bacterial contamination and include filtration to remove leukocytes and bacteria, diversion of the initial aliquot of blood during donation, and improved donor skin disinfection. Platelet pathogen inactivation methods under investigation include the addition of L-carnitine, gamma-irradiation, riboflavin plus UVA irradiation, and amotosalen HCl plus UVA irradiation. The latter process is licensed for clinical use with platelets in some countries in Europe. All of these approaches, either collectively or individually, hold considerable promise that the prevalence of adverse events associated with bacteria in platelet products will decline significantly in the very foreseeable future.
Automation↗
Proceedings of a consensus conference: the screening of blood donors for variant CJD.
Since the identification, in 1996, of the first case of variant Creutzfeldt-Jakob disease (vCJD) in humans various approaches have been implemented and/or proposed to prevent this disease from being transfusion transmitted. In addition, a variety of possible laboratory-based approaches have been developed and will continue to be developed for the vCJD screening of blood donors. Various issues related to the implementation of such vCJD testing is likely to assume greater importance as diagnostic tests for vCJD becomes available for the potential screening of blood donors. The purpose of this Consensus Conference was to bring together international experts in an effort to determine which principles should guide the introduction of such testing. These experts provided the scientific and biological background of bovine spongiform encephalopathy (BSE) and vCJD, an understanding of their current epidemiology, as well as the ethical and legal issues that would impact on the implementation of a screening test for preventing the transfusion transmission of vCJD. This contentious issue is of potential considerable importance to transfusion medicine personnel worldwide, as well as to future recipients of allogeneic blood components.
Animals↗
Hypotensive transfusion reactions can occur with blood products that are leukoreduced before storage.
BACKGROUND: Leukoreduction before storage, rather than bedside white blood cell filtration, is recommended to prevent hypotensive transfusion reactions. STUDY DESIGN AND METHODS: Investigation of hypotensive transfusion reactions during radical prostatectomy in two patients on angiotensin-converting enzyme inhibitors. In Patient A, hypotension occurred during the transfusion of each of the following blood products: 2 units of autologous blood deposited and leukoreduced (LR) before storage; 3 units of allogeneic red cells LR before storage; and 2 units of non-LR acute normovolemic hemodilution (ANH) whole blood. When each of the transfusions was stopped, the blood pressure recovered. In Patient B, hypotension occurred during the transfusion of non-LR ANH whole blood. All implicated units were administered rapidly using a blood infuser at 37 degrees C. Bradykinin (BK) and des-Arg9-BK formation and degradation and the activity of kinin-degrading metallopeptidases were measured in plasma samples from both patients. RESULTS: Degradation of des-Arg9-BK was severely impaired and the activity of aminopeptidase P severely reduced in Patient A, but not in Patient B. BK degradation was mildly impaired in both patients. CONCLUSION: Hypotensive reactions can occur with blood products that are LR before storage and non-LR ANH. An inherent defect in the metabolism of kinins may be a risk factor for the development of hypotensive transfusion reactions.
Adenocarcinoma↗
Clinical outcomes following institution of the Canadian universal leukoreduction program for red blood cell transfusions.
CONTEXT: A number of countries have implemented a policy of universal leukoreduction of their blood supply, but the potential role of leukoreduction in decreasing postoperative mortality and infection is unclear. OBJECTIVE: To evaluate clinical outcomes following adoption of a national universal prestorage leukoreduction program for blood transfusions. DESIGN, SETTING, AND POPULATION: Retrospective before-and-after cohort study conducted from August 1998 to August 2000 in 23 academic and community hospitals throughout Canada, enrolling 14 786 patients who received red blood cell transfusions following cardiac surgery or repair of hip fracture, or who required intensive care following a surgical intervention or multiple trauma. INTERVENTION: Universal prestorage leukoreduction program introduced by 2 Canadian blood agencies. A total of 6982 patients were enrolled during the control period and 7804 patients were enrolled following prestorage leukoreduction. MAIN OUTCOME MEASURES: All-cause in-hospital mortality and serious nosocomial infections (pneumonia, bacteremia, septic shock, all surgical site infections) occurring after first transfusion and at least 2 days after index procedure or intensive care unit admission. Secondary outcomes included rates of posttransfusion fever and antibiotic use. RESULTS: Unadjusted in-hospital mortality rates were significantly lower following the introduction of leukoreduction compared with the control period (6.19% vs 7.03%, respectively; P =.04). Compared with the control period, the adjusted odds of death following leukoreduction were reduced (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.75-0.99), but serious nosocomial infections did not decrease (adjusted OR, 0.97; 95% CI, 0.87-1.09). The frequency of posttransfusion fevers decreased significantly following leukoreduction (adjusted OR, 0.86; 95% CI, 0.79-0.94), as did antibiotic use (adjusted OR, 0.90; 95% CI, 0.82-0.99). CONCLUSION: A national universal leukoreduction program is potentially associated with decreased mortality as well as decreased fever episodes and antibiotic use after red blood cell transfusion in high-risk patients.
Adult↗
Clinical outcomes following institution of universal leukoreduction of blood transfusions for premature infants.
CONTEXT: Leukocytes present in stored blood products can have a variety of biological effects, including depression of immune function, thereby increasing nosocomial infections and possibly resulting in organ failure and death. Premature infants, given their immature immune state, may be uniquely predisposed to the effects of transfused leukocytes. OBJECTIVE: To evaluate the clinical outcomes following implementation of a universal prestorage red blood cell (RBC) leukoreduction program in premature infants admitted to neonatal intensive care units (NICUs). DESIGN AND SETTING: Retrospective before-and-after study conducted in 3 Canadian tertiary care NICUs from January 1998 to December 2000. PATIENTS: A total of 515 premature infants weighing less than 1250 g who were admitted to the NICU, received at least 1 RBC transfusion, and survived at least 48 hours were enrolled. The intervention group consisted of infants admitted in the 18-month period following the introduction of universal leukoreduction (n = 247) and the control group consisted of infants admitted during the 18 months prior to the introduction of universal leukoreduction (n = 268). MAIN OUTCOME MEASURES: Primary outcomes were nosocomial bacteremia and NICU mortality, compared before and after implementation of universal leukoreduction using multivariate regression. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. RESULTS: The proportion of infants who acquired bacteremia after an RBC transfusion was 79/267 (29.6%) in the nonleukoreduction period and 63/246 (25.6%) in the leukoreduction period. For NICU mortality, there were 45 deaths (16.8%) in the nonleukoreduction period and 44 deaths (17.8%) in the leukoreduction period. The adjusted odds ratio (OR) for bacteremia was 0.59 (95% confidence interval [CI], 0.34-1.01) and for mortality was 1.22 (95% CI, 0.59-2.50). The adjusted ORs for bronchopulmonary dysplasia and retinopathy of prematurity were 0.42 (95% CI, 0.25-0.70) and 0.56 (95% CI, 0.33-0.93), respectively. The adjusted ORs for necrotizing enterocolitis and grade 3 or 4 intraventricular hemorrhage were 0.39 (95% CI, 0.17-0.90) and 0.65 (95% CI, 0.35-1.19), respectively. The adjusted OR for a composite measure of any major neonatal morbidity was 0.31 (95% CI, 0.17-0.56). Crude and adjusted rates for all secondary outcomes suggest that leukoreduction was associated with improved outcomes. CONCLUSION: Implementation of universal prestorage leukoreduction was not associated with significant reductions in NICU mortality or bacteremia but was associated with improvement in several clinical outcomes in premature infants requiring RBC transfusions.
Bacteremia↗
Recombinant factor VIIa reduces bleeding in severely thrombocytopenic rabbits.
Severe thrombocytopenia is a common complication to intensive chemotherapeutic regimens. For bleeding episodes associated with severe thrombocytopenia, the current standard treatment is platelet transfusion. However, due to several transfusion complications such as transfusion-transmitted diseases, platelet refractoriness and immunomodulation, as well as increasing problems with sufficient supply of platelet products, it is imperative to search for alternatives to platelet transfusion. To test the efficacy of recombinant activated human coagulation factor VII (rFVIIa, NovoSeven) in thrombocytopenia, a preclinical study was conducted in thrombocytopenic rabbits. Thrombocytopenia was induced by a combination of gamma-irradiation and the use of platelet antibodies, and the effect of rFVIIa on nail cuticle bleeding was determined. Administration of rFVIIa at 2 mg/kg significantly shortened the prolonged bleeding time in thrombocytopenic animals (rFVIIa vs. control, median 23 min 41 s vs. 60 min, p=0.016) as well as significantly reducing the blood loss (rFVIIa vs. control, median: 8.8 vs. 12.2 nmol hemoglobin/ml, p=0.016). This effect was also reflected by a significant reduction of the prothrombin time, activated partial thromboplastin time, as well as improvement in clotting parameters in an in vitro thromboelastography thrombocytopenia model. Histopathological evaluation of kidney biopsies for the presence of micro thrombi did not reveal evidence of prothrombotic effects of rFVIIa in this model. These data demonstrate the haemostatic efficacy of rFVIIa in a rabbit model of severe thrombocytopenia. Clinical trials will be needed to further explore the potential of NovoSeven as a haemostatic agent in thrombocytopenic patients.
Animals↗