Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients.
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ABSTRACT:
SUBMITTER: Pietropaoli AP
PROVIDER: S-EPMC6548617 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients.
Pietropaoli Anthony P AP Henrichs Kelly F KF Cholette Jill M JM Spinelli Sherry L SL Phipps Richard P RP Refaai Majed A MA Blumberg Neil N
Transfusion 20190227 6
<h4>Background</h4>Relationships between red blood cell (RBC) transfusion, circulating cell-free heme, and clinical outcomes in critically ill transfusion recipients are incompletely understood. The goal of this study was to determine whether total plasma heme increases after RBC transfusion and predicts mortality in critically ill patients.<h4>Study design and methods</h4>This was a prospective cohort study of 111 consecutive medical intensive care patients requiring RBC transfusion. Cell-free ...[more]
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Project description:Red blood cells (RBC) storage facilitates the supply of RBC to meet the clinical demand for transfusion and to avoid wastage. However, RBC storage is associated with adverse changes in erythrocytes and their preservation medium. These changes are responsible for functional alterations and for the accumulation of potentially injurious bioreactive substances. They also may have clinically harmful effects especially in critically ill patients. The clinical consequences of storage lesions, however, remain a matter of persistent controversy. Multiple retrospective, observational, and single-center studies have reported heterogeneous and conflicting findings about the effect of blood storage duration on morbidity and/or mortality in trauma, cardiac surgery, and intensive care unit patients. Describing the details of this controversy, this review not only summarizes the current literature but also highlights the equipoise that currently exists with regard to the use of short versus current standard (extended) storage duration red cells in critically ill patients and supports the need for large, randomized, controlled trials evaluating the clinical impact of transfusing fresh (short duration of storage) versus older (extended duration of storage) red cells in critically ill patients.
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Project description:OBJECTIVES:Little is known about platelet transfusions in pediatric critical illness. We sought to describe the epidemiology, indications, and outcomes of platelet transfusions among critically ill children. DESIGN:Prospective cohort study. SETTING:Multicenter (82 PICUs), international (16 countries) from September 2016 to April 2017. PATIENTS:Children ages 3 days to 16 years prescribed a platelet transfusion in the ICU during screening days. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Over 6 weeks, 16,934 patients were eligible, and 559 received at least one platelet transfusion (prevalence, 3.3%). The indications for transfusion included prophylaxis (67%), minor bleeding (21%), and major bleeding (12%). Thirty-four percent of prophylactic platelet transfusions were prescribed when the platelet count was greater than or equal to 50 × 10 cells/L. The median (interquartile range) change in platelet count post transfusion was 48 × 10 cells/L (17-82 × 10 cells/L) for major bleeding, 42 × 10 cells/L (16-80 × 10 cells/L) for prophylactic transfusions to meet a defined threshold, 38 × 10 cells/L (17-72 × 10 cells/L) for minor bleeding, and 25 × 10 cells/L (10-47 × 10 cells/L) for prophylaxis in patients at risk of bleeding from a device. Overall ICU mortality was 25% but varied from 18% to 35% based on indication for transfusion. Upon adjusted analysis, total administered platelet dose was independently associated with increased ICU mortality (odds ratio for each additional 1 mL/kg platelets transfused, 1.002; 95% CI, 1.001-1.003; p = 0.005). CONCLUSIONS:The majority of platelet transfusions are given as prophylaxis to nonbleeding children, and significant variation in platelet thresholds exists. Studies are needed to clarify appropriate indications, with focus on prophylactic transfusions.
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Project description:Critically ill patients frequently receive plasma transfusion under the assumptions that abnormal coagulation test results confer increased risk of bleeding and that plasma transfusion will decrease this risk. However, the effect of prophylactic plasma transfusion remains poorly understood. The objective of this study was to determine the relationship between prophylactic plasma transfusion and bleeding complications in critically ill patients.This is a retrospective cohort study of adults admitted to the intensive care unit (ICU) at a single academic institution between January 1, 2009 and December 31, 2013. Inclusion criteria included age ?18 years and an international normalized ratio measured during ICU admission. Multivariable propensity-matched analyses were used to evaluate associations between prophylactic plasma transfusion and outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of hospital- and ICU-free days and mortality within 30 days of ICU discharge.A total of 27,561 patients were included in the investigation with 2472 (9.0%) receiving plasma therapy and 1105 (44.7%) for which plasma transfusion was prophylactic in nature. In multivariable propensity-matched analyses, patients receiving plasma had higher rates of red blood cell transfusion (odds ratio: 4.3 [95% confidence interval: 3.3-5.7], P < .001) and fewer hospital-free days (estimated % increase: -11.0% [95% confidence interval: -11.4, -10.6%], P < .001). There were no significant differences in ICU-free days or mortality. These findings appeared robust, persisting in multiple predefined sensitivity analyses.Prophylactic administration of plasma in the critically ill was not associated with improved clinical outcomes. Further investigation examining the utility of plasma transfusion in this population is warranted.
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Project description:Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) commonly complicate transfusion in critically ill patients. Prior outcome studies of TACO and TRALI have focused on short-term morbidity and mortality, but the long-term survival and quality of life (QOL) of these patients remain unknown.In a nested case-control study, we compared survival and QOL between critically ill medical patients who developed pulmonary edema after transfusion (TRALI or TACO) and medical critically ill transfused controls, matched by age, gender, and admission diagnostic group. QOL in survivors was assessed with a 36-item short form health survey 1 year after initial hospitalization.Hospital, 1-year, and 2-year mortality among the 74 TRALI cases and 74 matched controls were 43.2% vs 24.3% (P = .020), 63.8% vs 46.4% (P = .037) and 74.3% vs 54.3% (P = .031), whereas among the 51 TACO cases and 51 matched controls these values were 7.8% vs 11.8% (P = .727), 38.0% vs 28.0% (P = .371), and 44.9% vs 38.8% (P = .512). When adjusted for age and baseline severity of illness in a Cox proportional hazard analysis, the development of TRALI remained associated with decreased survival (hazard ratio 1.86; 95% CI, 1.19-2.93; P = .006). Both TRALI (P = .006, P = .03) and TACO (P = .03, P = .049) were associated with prolonged ICU and hospital lengths of stay.In critically ill medical patients, development of TRALI, but not TACO, is independently associated with decreased long-term survival.
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Project description:BackgroundObservational studies suggest that sex-mismatched transfusion is associated with increased mortality. Mechanisms driving mortality are not known but may include endothelial activation. The aim of this study is to investigate the effects of sex-mismatched red blood cell (RBC) transfusions on endothelial cell activation markers in critically ill patients.Study design and methodsIn patients admitted to the intensive care unit who received a single RBC unit, blood samples were drawn before (T0), 1 h after (T1), and 24 h after transfusion (T24) for analysis of soluble syndecan-1, soluble intercellular adhesion molecule-1, soluble thrombomodulin (sTM), von Willebrand factor antigen, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα). Changes in the levels of these factors were compared between sex-matched and sex-mismatched groups.ResultsOf 69 included patients, 32 patients were in the sex-matched and 37 patients were in the sex-mismatched group. Compared to baseline, sex-matched transfusion was associated with significant reduction in sTM level (p value = 0.03). Between-group comparison showed that levels of syndecan-1 and sTM were significantly higher in the sex-mismatched group compared to the sex-matched group at T24 (p value = 0.04 and 0.01, respectively). Also, TNFα and IL-6 levels showed a statistically marginal significant increase compared to baseline in the sex-mismatched group at T24 (p value = 0.06 and 0.05, respectively), but not in the sex-matched group.DiscussionTransfusion of a single sex-mismatched RBC unit was associated with higher syndecan-1 and sTM levels compared to transfusion of sex-matched RBC unit. These findings may suggest that sex-mismatched RBC transfusion is associated with endothelial activation.
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Project description:BACKGROUND:The aim was to describe transfusion practice in critically ill patients at an international level and evaluate the effects of red blood cell (RBC) transfusion on outcomes in these patients. METHODS:This was a pre-planned sub-study of the Intensive Care Over Nations audit, which involved 730 ICUs in 84 countries and included all adult patients admitted between 8 May and 18 May 2012, except admissions for routine postoperative surveillance. RESULTS:ICU and hospital outcomes were recorded. Among the 10,069 patients included in the audit, data related to transfusion had been completed for 9553 (mean age 60?±?18 years, 60% male); 2511 (26.3%) of these had received a transfusion, with considerable variation among geographic regions. The mean lowest hemoglobin on the day of transfusion was 8.3?±?1.7 g/dL, but varied from 7.8?±?1.4 g/dL in the Middle East to 8.9?±?1.9 g/dL in Eastern Europe. Hospital mortality rates were higher in transfused than in non-transfused patients (30.0% vs. 19.6%, p?<?0.001) and increased with increasing numbers of transfused units. In an extended Cox proportional hazard analysis, the relative risk of in-hospital death was slightly lower after transfusion in the whole cohort (hazard ratio 0.98, confidence interval 0.96-1.00, p?=?0.048). There was a stepwise decrease in the hazard ratio for mortality after transfusion with increasing admission severity scores. CONCLUSIONS:More than one fourth of critically ill patients are transfused during their ICU stay, with considerable variations in transfusion practice among geographic regions. After adjustment for confounders, RBC transfusions were associated with a slightly lower relative risk of in-hospital death, especially in the most severely ill patients, highlighting the importance of taking the severity of illness into account when making transfusion decisions.
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Project description:Rationale: In critically ill patients, a hemoglobin transfusion threshold of <7.0 g/dl compared with <10.0 g/dl improves organ dysfunction. However, it is unclear if transfusion at a hemoglobin of <7.0 g/dl is superior to no transfusion. Objectives: To compare degrees of organ dysfunction between transfusion and no transfusion at a hemoglobin threshold of <7.0 g/dl among critically ill patients using quasiexperimental regression discontinuity methods. Methods: We performed regression discontinuity analysis using hemoglobin measurements from patients admitted to intensive care units in three cohorts (Medical Information Mart for Intensive Care IV, eICU, and Premier Inc.), estimating the change in organ dysfunction (modified sequential organ failure assessment score) in the 24- to 72-hour window following each hemoglobin measurement. We compared hemoglobin concentrations just above and below 7.0 g/dl using a "fuzzy" discontinuity approach, based on the concept that measurement noise pseudorandomizes similar hemoglobin concentrations on either side of the transfusion threshold. Results: A total of 11,181, 13,664, and 167,142 patients were included in the Medical Information Mart for Intensive Care IV (MIMIC-IV), eICU, and Premier Inc. cohorts, respectively. Patient characteristics below the threshold did not differ from those above the threshold, except that crossing below the threshold resulted in a >20% absolute increase in transfusion rates in all three cohorts. Transfusion was associated with increases in hemoglobin concentration in the subsequent 24-72 hours (MIMIC-IV, 2.4 [95% confidence interval (CI), 1.1 to 3.6] g/dl; eICU, 0.7 [95% CI, 0.3 to 1.2] g/dl; Premier Inc., 1.9 [95% CI, 1.5 to 2.2] g/dl) but not with improvement in organ dysfunction (MIMIC-IV, 4.6 [95% CI, -1.2 to 10] points; eICU, 4.4 [95% CI, 0.9 to 7.8] points; Premier Inc., 1.1 [95% CI, -0.2 to 2.3] points) compared with no transfusion. Conclusions: Transfusion was not associated with improved organ dysfunction compared with no transfusion at a hemoglobin threshold of 7.0 g/dl, suggesting that evaluation of transfusion targets other than a hemoglobin threshold of 7.0 g/dl may be warranted.
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Project description:In healthy adults, transfusion of older stored red blood cells (RBCs) produces extravascular hemolysis and circulating non-transferrin-bound iron. In a prospective, observational study of critically ill children, we examined the effect of RBC storage duration on the extent of hemolysis by comparing laboratory measurements obtained before, and 4 hr after, RBC transfusion (N?=?100) or saline/albumin infusion (N?=?20). Transfusion of RBCs stored for longer than 4 weeks significantly increased plasma free hemoglobin (P?<?0.05), indirect bilirubin (P?<?0.05), serum iron (P?<?0.001), and non-transferrin-bound iron (P?<?0.01). However, days of storage duration poorly correlated (R(2) <0.10) with all measured indicators of hemolysis and inflammation. These results suggest that, in critically ill children, most effects of RBC storage duration on post-transfusion hemolysis are overwhelmed by recipient and/or donor factors. Nonetheless, we identified a subset of patients (N?=?21) with evidence of considerable extravascular hemolysis (i.e., increased indirect bilirubin ?0.4 mg/dL). In these patients, transfusion-associated hemolysis was accompanied by increases in circulating non-transferrin-bound iron and free hemoglobin and by an acute phase response, as assessed by an increase in median C-reactive protein levels of 21.2 mg/L (P?<?0.05). In summary, RBC transfusions were associated with an acute phase response and both extravascular and intravascular hemolysis, which were independent of RBC storage duration. The 21% of transfusions that were associated with substantial hemolysis conferred an increased risk of inducing an acute phase response.
| S-EPMC4831067 | biostudies-literature
Project description:BACKGROUND:Some countries have limited the maximum allowable storage duration for red cells to 5 weeks before transfusion. In the US, red blood cells can be stored for up to 6 weeks, but randomized trials have not assessed the effects of this final week of storage on clinical outcomes. METHODS:Sixty healthy adult volunteers were randomized to a single standard, autologous, leukoreduced, packed red cell transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage (n = 10 per group). 51-Chromium posttransfusion red cell recovery studies were performed and laboratory parameters measured before and at defined times after transfusion. RESULTS:Extravascular hemolysis after transfusion progressively increased with increasing storage time (P < 0.001 for linear trend in the AUC of serum indirect bilirubin and iron levels). Longer storage duration was associated with decreasing posttransfusion red cell recovery (P = 0.002), decreasing elevations in hematocrit (P = 0.02), and increasing serum ferritin (P < 0.0001). After 6 weeks of refrigerated storage, transfusion was followed by increases in AUC for serum iron (P < 0.01), transferrin saturation (P < 0.001), and nontransferrin-bound iron (P < 0.001) as compared with transfusion after 1 to 5 weeks of storage. CONCLUSIONS:After 6 weeks of refrigerated storage, transfusion of autologous red cells to healthy human volunteers increased extravascular hemolysis, saturated serum transferrin, and produced circulating nontransferrin-bound iron. These outcomes, associated with increased risks of harm, provide evidence that the maximal allowable red cell storage duration should be reduced to the minimum sustainable by the blood supply, with 35 days as an attainable goal.REGISTRATION. ClinicalTrials.gov NCT02087514. FUNDING:NIH grant HL115557 and UL1 TR000040.
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