Prospective validation of the EuroSCORE II risk model in a single Dutch cardiac surgery centre.

OBJECTIVE: The EuroSCORE I was one of the most frequently used pre-operative risk models in cardiac surgery. In 2011 it was replaced by its successor the EuroSCORE II. This study aims to validate the EuroSCORE II and to compare its performance with the EuroSCORE I in a Dutch hospital. METHODS: The EuroSCORE II was prospectively validated in 2,296 consecutive cardiac surgery patients between 1 April 2012 and 1 January 2014. Receiver operating characteristic curves on in-hospital mortality were plotted for EuroSCORE I and EuroSCORE II, and the area under the curve was calculated to assess discriminative power. Calibration was assessed by comparing observed versus expected mortality. Additionally, analyses were performed in which we stratified for type of surgery and for elective versus emergency surgery. RESULTS: The observed mortality was 2.4% (55 patients). The discriminative power of the EuroSCORE II surpassed that of the EuroSCORE I (area under the curve EuroSCORE II 0.871, 95% confidence interval (CI) 0.832-0.911; area under the curve additive EuroSCORE I 0.840, CI 0.798-0.882; area under the curve logistic EuroSCORE I 0.761, CI 0.695-0.828). Both the additive and the logistic EuroSCORE I overestimated mortality (predictive mortality additive EuroSCORE I median 5.0%, inter-quartile range 3.0-8.0%; logistic EuroSCORE I 10.7%, inter-quartile range 5.8-13.9), while the EuroSCORE II underestimated mortality (median 1.6%, inter-quartile range 1.0-3.5). In most stratified analyses the EuroSCORE II performed better. CONCLUSION: Our results show that the EuroSCORE II produces a valid risk prediction and outperforms the EuroSCORE I in elective cardiac surgery patients.

Implementation of a new platelet pooling system for platelet concentrates led to a higher corrected count increment after transfusion: a comparative observational study of platelet concentrates before and after implementation.

OBJECTIVES: To study the effect of extended storage of platelet concentrates (PCs) and the implementation of a new platelet pooling system for PCs on corrected count increment (CCI) after transfusion. BACKGROUND: Due to new developments and changes in processes or procedures, one should remain alert for the effects of these changes. Besides in vitro studies and validation, in vivo studies are also important, as it has been shown that in vitro results do not always predict in vivo outcomes. METHODS/MATERIALS: After introduction of extended storage of PCs for 5-7 days prepared from five buffy coats and plasma, transfusion monitoring for transfusions of PCs in haemato-oncological patients was set up. After 9 months, a new pooling system for PCs was implemented, Composelect instead of Optipure PLT, and transfusion monitoring was continued for another 8 months. The CCI was used as primary outcome. RESULTS: In total, 93 patients were included and transfused with PCs prepared in the Optipure PLT system (262 transfusions) or in the Composelect system (127 transfusions). Extended storage of PCs for 7 days had no significant effect on CCI. Although the implementation of the Composelect system did not influence the CCI1 h (13.8 ± 6.0 vs. 13.0 ± 5.8; n.s.), it seemed to have a positive effect on CCI24 h (7.0 ± 4.9 vs. 4.7 ± 4.5; P < 0.05). CONCLUSION: Although the influence of confounders could not be excluded, it seemed that implementation of the Composelect system for PCs led to an improved CCI24 h and that extended storage of PCs did not influence the CCI.

Variation between hospitals in rates of reported transfusion reactions: is a high reporting rate an indicator of safer transfusion?

BACKGROUND AND OBJECTIVES: It has been suggested that the rate of reported transfusion reactions is positively correlated with safety of the transfusion chain in a hospital. We evaluated this assumption in the Transfusion Reactions in Patients Dutch National Hemovigilance Office database taking reported incorrect blood component transfused as a proxy for unsafe transfusion. METHODS: Reports from 2006 to 2010 and annual numbers of transfused blood components from the 103 hospitals were analysed. The rate of transfusion reactions per 1000 blood components was calculated per hospital. Logistic regression analysis was performed between reporting of at least one incorrect blood component and tertile of transfusion reaction rate. RESULTS: Out of the 103 hospitals, 101 had complete data in some and 93 in all 5years. In all, 72 had reported at least one incorrect blood component transfused; this was associated with blood use level and also with rate of reported transfusion reactions: odds ratio 4·2 (95% confidence interval, 1·3-13·7) in the highest vs. the lowest tertile after adjustment for blood use level. CONCLUSION: Hospitals in the Netherlands which report more transfusion reactions per 1000 units are also more likely to have reported incorrect blood component transfused. The data do not support that hospitals with a higher rate of transfusion reaction reports are safer.

Red cell storage and prognosis.

During storage of red blood cells (RBC), these cells develop storage lesions. The clinical relevance of these storage lesions is heavily discussed in literature. In this review, different aspects of the storage lesion are shown and how these potentially affect posttransfusion performance of the RBC. An overview of the conflicting literature on the clinical relevance of prolonged storage is given, summarizing the evidence on associations with mortality, length of stay, (postoperative) infections and organ failure. Subsequently, possible explanations are given for the conflicting results in the clinical studies and suggestions on how to proceed.

Evaluation of noninvasive methods for the estimation of haemoglobin content in red blood cell concentrates.

OBJECTIVES: Red blood cell concentrates (RCCs) are the major blood component transfused to patients. There is a great variability in patient response, depending on both the patient's blood volume and haemoglobin content in the RCC. Standardisation of transfusion practice is needed to improve the prediction of patient outcome. AIM: We hypothesise that labelling of RCCs with haemoglobin content will add possibilities for the standardisation of transfusion practice. METHODS: Data from multiple international transfusion services regarding haemoglobin content and weight or volume of RCC were collected and analysed. RESULTS: We demonstrate a strong and highly significant correlation between haemoglobin content with both weight and volume of the RCCs. A linear regression model was used to assess these relationships, and it demonstrates how haemoglobin content can be estimated for different cell production processes. CONCLUSIONS: We recommend the use of weight or volume of the RCCs as the basis of estimating haemoglobin in the RCC and postulate that this can be used in future studies to explore the effects of a haemoglobin dose-based transfusion system. As the weight - and sometimes the volume - of the blood bag is easily accessible, in contrast to direct haemoglobin measurements from each individual unit, this method is feasible and simple.

The effect of RBC transfusions on cytokine gene expression after cardiac surgery in patients developing post-operative multiple organ failure.

AIM: To determine the effect of red blood cell (RBC) transfusions during cardiac surgery on cytokine gene expression (GE) in relation to multiple organ failure (MOF) development after systemic inflammatory response syndrome (SIRS). BACKGROUND: RBC transfusion in cardiac surgery patients is dose-dependently associated with post-operative MOF, possibly acting as a second hit after cardiopulmonary bypass. METHODS: For this observational study, 29 patients divided into four groups of cardiac surgery patients were selected from a randomised controlled trial (RCT). Group 1: no-RBC, no-MOF (N = 8); group 2: MOF, no-RBC (N = 7); group 3: RBC, no-MOF (N = 6); group 4: RBC and MOF (N = 8). Selection was based on age, gender, number of (leukocyte-depleted) RBC transfusions, type and duration of surgery. A 114 cytokine GE array was applied to blood samples withdrawn before and 24 h after surgery. Expression of selected genes was confirmed with reverse transcriptase real time-polymerase chain reaction (RT-PCR). RESULTS: Nineteen of the 39 detectable genes showed a significant change in GE after surgery. Confirmed by RT-PCR, transfused MOF patients exhibit significantly less downregulation of CD40 ligand than control patients. Patients who would develop MOF show significantly larger increases in GE of transforming growth factor-α (TGF-α), tumour necrosis factor (TNF)-superfamily members 10 and 13B (TNFsf10/13B). CONCLUSIONS: When tested at 24 h after surgery, cytokine GE in peripheral blood leucocytes showed no significant differences between those transfused and those not transfused. Some alterations were seen in those developing MOF compared to those who did not, but the findings offer no role of leukocyte depleted (LD) RBC transfusion in the development of MOF.

Prevalence and specificities of red blood cell alloantibodies in transfused Ugandans with different diseases.

BACKGROUND AND OBJECTIVES: Alloantibody formation against red blood cell (RBC) antigens is a common complication of transfusion therapy. However, the prevalence of RBC alloimmunization is hardly known in Black Africans. In Uganda, the practice is to transfuse ABO/D compatible blood without screening for immune antibodies. The aim of this study was to determine the prevalence and specificities of RBC alloantibodies in transfused Ugandans. MATERIALS AND METHODS: Using a cross-sectional design, transfused patients at Mulago Hospital in Kampala, Uganda were investigated. Demographic characteristics and transfusion histories were recorded. EDTA blood samples were obtained from consenting patients and RBC alloimmunization was demonstrated using immunohaematological tests. RESULTS: A total of 214 transfused patients (mean age, 30.3 years; F/M ratio, 1.0) were investigated. Thirteen patients (6.1%) possessed RBC alloantibodies whose specificities were six anti-E; three anti-S; one each of anti-D, -K and -Le(a); and two samples were pan-reactive. Eleven (84.6%) of the alloimmunized patients had experienced up to 10 transfusion episodes. The number of units of blood transfused and the transfusion episodes were significantly associated with the RBC alloimmunization rate (P = 0.01). CONCLUSIONS: The prevalence of RBC alloimmunization in transfused Ugandans was 6.1% and was associated with the number of donor exposures. This immunization rate is similar to that observed in transfused Caucasians despite differences in RBC antigen distributions. Patients with malaria were less likely to develop RBC alloantibodies. Alloantibodies were mainly against E and S antigens. We recommend the introduction of pretransfusion antibody tests in Uganda depending on the recipient's diagnosis.

Leucocyte depletion of perioperative blood transfusion does not affect long-term survival and recurrence in patients with gastrointestinal cancer.

BACKGROUND: Perioperative red blood cell (RBC) transfusion may be associated with a poor prognosis in cancer surgery. Allogeneic leucocytes are assumed to play a causal role. This study evaluated the long-term effect of transfusion with leucocyte-depleted (LD) blood in patients with gastrointestinal cancer. METHODS: The Transfusion Associated Complications = Transfusion Induced Complications? (TACTIC) study is a multicentre randomized controlled trial evaluating the short-term benefits of LD versus non-LD RBC transfusions. The present study evaluated 5-year survival and cancer recurrence among 512 patients with gastrointestinal cancer included in the TACTIC study. RESULTS: Some 89.2 per cent of patients had a primary tumour and 79.7 per cent underwent surgery with curative intent; 243 patients received perioperative RBC transfusion (median 3 units). The 5-year overall survival rate of patients with any type of gastrointestinal cancer was 50.8 per cent in the LD group and 45.8 per cent in the non-LD group (P = 0.191). Corresponding 5-year disease-free survival rates were 60.0 and 56.6 per cent (P = 0.482), and recurrence rates 32.9 and 34.3 per cent (P = 0.864). CONCLUSION: Leucocyte depletion is not associated with better long-term survival and lower recurrence rates in patients with gastrointestinal cancer.

Double-blind, randomized controlled trial on the effect of leukocyte-depleted erythrocyte transfusions in cardiac valve surgery.

BACKGROUND: Leukocytes in allogeneic blood transfusions are believed to be the cause of immunomodulatory events. A few trials on leukocyte removal from transfusions in cardiac surgery have been conducted, and they showed inconclusive results. We found in a previous study a decrease in mortality rates and number of infections in a subgroup of more heavily transfused patients. METHODS AND RESULTS: Patients (n=496) undergoing valve surgery (with or without CABG) were randomly assigned in a double-blind fashion to receive standard buffy coat-depleted (PC) or prestorage, by filtration, leukocyte-depleted erythrocytes (LD). The primary end point was mortality at 90 days, and secondary end points were in-hospital mortality, multiple organ dysfunction syndrome, infections, intensive care unit stay, and hospital stay. The difference in mortality at 90 days was not significant (PC 12.7% versus LD 8.4%; odds ratio [OR], 1.52; 95% confidence interval [CI], 0.84 to 2.73). The in-hospital mortality rate was almost twice as high in the PC group (10.1% versus 5.5% in the LD group; OR, 1.99; 95% CI, 0.99 to 4.00). The incidence of multiple organ dysfunction syndrome in both groups was similar, although more patients with multiple organ dysfunction syndrome died in the PC group. LD was associated with a significantly reduced infection rate (PC 31.6% versus LD 21.6%; OR, 1.64; 95% CI, 1.08 to 2.49). In both groups, intensive care unit stay and hospital stay were similar, and postoperative complications increased with the number of transfused units. CONCLUSIONS: Mortality at 90 days was not significantly different; however, a beneficial effect of LD in valve surgery was found for the secondary end points of in-hospital mortality and infections.

Clinical effects of leucoreduction of blood transfusions.

For many years filtration for removal of leucocytes from red blood cell (RBC) and platelet transfusions was applied for selected patients to prevent cytomegalovirus (CMV) (re)activation, HLA immunisation and recurrent febrile nonhaemolytic transfusion reactions (FNHTR ). Since the 1980s, there was also growing concern about cancer recurrence and postoperative infections. In this review we discuss the studies on possible benefits of leucoreduction. In 2001 the Dutch Health Council decided that all blood products should undergo leucoreduction by filtration, as a precautionary measure to reduce possible transmission of variant Creutzfeld-Jacob disease (vCJD). The incidences of transfusion-transmitted CMV infection, HLA immunisation and FN HTR are decreased by universal leucoreduction. However, transfusion-related immunomodulation with presumed negative effects on cancer immunosurveillance, postoperative infections or aggravating organ failure, investigated in randomised controlled trials, revealed no support for extended indications for leucoreduction. An exception was seen in cardiac surgery where leucoreduction reduced short-term mortality by approximately 50%. The exact mechanism(s) for this effect is (are) not known. Pro-inf lammatory cytokines induced by eucocytecontaining RBC transfusions in combination with the inflammatory response after cardiac surgery may aggravate morbidity and could lead to mortality. In this review we discuss the evidence for the benefits of universal leucoreduction. Based on the available evidence, reversal to the use of buffy-coat depleted RBCs and restricted indications for leucoreduction by filtration (extended with open-heart surgery) is a safe option.

Is increased mortality associated with post-operative infections after leukocytes containing red blood cell transfusions in cardiac surgery? An extended analysis.

In two randomized trials in cardiac surgery we observed that leukoreduced allogeneic red blood cell (RBC) transfusions (LR) compared with standard buffy-coat-depleted RBC transfusions (BCD) resulted in lower rates of post-operative infections and mortality. To unravel whether this comprises two independent side effects or could be related complications of allogeneic leukocytes, we performed a re-analysis on the patients of these two trials. For all analyses, homogeneity tests were shown not to be significant. Data on characteristics of post-operative infections, nature of microorganisms, number of transfusions and causes of death in both studies were subjected to an integrated analysis. In both studies combined, 1085 patients had been assigned to prestorage leukoreduced RBCs (LR, n= 542) or standard buffy-coat-depleted RBCs (BCD, n= 543). Post-operative infections were significantly higher in the BCD group [BCD: 34.2% vs. LR: 24.0%, common odds ratios (COR): 1.65, 95% confidence interval (CI): 1.27-2.15], whereas the species of cultured microorganisms and the type of the infections were similar in both randomization arms. Mortality with infections was significantly higher in patients receiving BCD compared with LR (BCD: 5.5% vs. LR: 2.2%, COR: 2.59, 95% CI: 1.31-5.14), whereas mortality without infections was similar in both arms (BCD: 3.9% vs. LR: 3.1%, COR: 1.24, 95% CI: 0.65-2.38). The only cause of death that differed significantly between BCD and LR was the combination of multiple organ dysfunction syndrome with infections. This re-analysis shows that transfusion of leukocytes containing RBCs during cardiac surgery may be associated with more infections with fatal outcome. This should be confirmed in a larger extended analysis or a prospective study.

Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery.

Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.

Effects of leukocyte depletion of blood transfusions on postoperative complications.

Postoperative complications associated with blood transfusions are frequently reported to be a result of the transfused leukocytes. This paper examines the effects of leukocyte depletion. Leukocyte depletion by filtration which can reduce leukocyte presence by more than 99.9%. The implications of this are postulated in terms of the results that may be obtained.

Clinical significance of leukoreduktion of blood components.

The clinical significance of leukocyte reduction of all blood components must be deducted from patients transfused in the surgical setting. Under these circumstances many factors contribute to morbidity and mortality, while such factors can be candidates for confounders. Moreover, to investigate effects on infrequent events such as post-operative mortality and multiple organ dysfunction syndrome, large patient cohorts must be studied. Our studies suggest that leukocytes or leukocyte aggregates in red cell transfusions indeed may be harmful if larger dosages are administered under certain clinical circumstances. A critical leukocyte load seems to start with approximately 2.5 x 10(9). Reducing the leukocyte contamination of red cell components, not necessarily by filtration, may benefit patients who require multiple transfusions within a short time interval.

Perioperative blood transfusions, with or without allogeneic leucocytes, relate to survival, not to cancer recurrence.

BACKGROUND: Perioperative blood transfusions are reported to be related to cancer recurrence and reduced survival. Different underlying mechanisms have been proposed, and allogeneic leucocytes in transfused blood have been suggested to contribute to this phenomenon. METHODS: Packed red cells without buffy coat (PC group) were compared with filtered, leucoreduced, red cells (LD group) in a randomized trial of 697 patients with colorectal carcinoma. Five-year survival and cancer recurrence rates were determined, with special emphasis on the location of recurrence. RESULTS: The intention-to-treat analysis showed a survival rate of 63.6 per cent in the PC group and 65.3 per cent in the LD group (P = 0.69), with recurrence rates of 27.8 and 27.9 per cent respectively. The observational analysis showed a significant difference in survival between transfused and non-transfused patients (59.6 versus 72.9 per cent; P < 0.001). The difference in cancer recurrence rate between transfused and non-transfused patients was not statistically significant (29.8 versus 24.3 per cent; P = 0.13). Local recurrences were more frequent in transfused than non-transfused patients (11.9 versus 7.6 per cent; P = 0.09). CONCLUSION: Leucocyte depletion of perioperative transfused blood has no effect on long-term survival and/or cancer recurrence. Perioperative blood transfusions are associated with impaired survival, but not with cancer recurrence. The slight increase in local recurrence rate in transfused patients appears to be related to complicated, in particular rectal, surgery.

Antibodies against p53 are associated with poor prognosis of colorectal cancer.

Mutation of the p53 gene is a common event in colorectal cancer. This alteration can result in cellular accumulation of p53 and may also induce p53 antibodies. Accumulation of p53 in tumour cells has been associated with poor prognosis of colorectal cancer. We tested preoperative sera from 255 patients with colorectal cancer by enzyme-linked immunosorbent assay (ELISA). A total of 70.2% had reactivity that was higher than the 'low' control serum. Employing a cut-off level of 10% of the 'high' control sample, 25.5% of the patients were positive for p53 antibodies. The presence of p53 antibodies correlated with the following prognostic factors: histological differentiation grade, shape of the tumour, and tumour invasion into blood vessels. Patients with p53 antibodies were shown to have decreased survival and decreased disease-free survival. Specifically for patients with cancer stage A and B1 the presence of p53 antibodies selected a subgroup with poor prognosis.

Randomised controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer.

In retrospective studies, perioperative blood transfusions were associated with poor prognosis after surgery for cancer and were a major independent risk factor for postoperative bacterial infection. Leucocyte-depleted, in contrast to buffy-coat-depleted, blood has no immunosuppressive effects in transplantation and so might lack detrimental effects on cancer prognosis and postoperative infections. We studied this hypothesis in a controlled trial by randomly allocating patients to receive either leucocyte-depleted red cells or packed cells without buffy coat when blood was needed. Between 1987 and 1990, 871 eligible patients with colorectal cancer, including 697 patients operated upon with curative intent, were randomised in the 16 participating hospitals. Neither the eligible group nor the curative group showed significant differences between the two trial transfusions in survival, disease-free survival, cancer recurrence rates, or overall infection rates after an average follow-up of 36 months. Patients who had a curative resection and who received blood of any sort had a lower 3-year survival than non-transfused patients (69% vs 81%, p = 0.001) and a higher infection rate (39% vs 24%, p < 0.001). Colorectal cancer recurrence rates, however, were not influenced by blood transfusion (30% vs 26%, p = 0.22). These combined observations confirm the association between blood transfusion and poor patient survival but indicate that the relation is not due to promotion of cancer.

Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery: a randomized clinical trial.

BACKGROUND: Leukocytes in transfused blood are associated with several posttransfusion immunomodulatory effects. Although leukocytes play an important role in reperfusion injury, the contribution of leukocytes in transfused blood products has not been investigated. To estimate the role and the timing of leukocyte filtration of red cells in cardiac surgery, we performed a randomized study. METHODS AND RESULTS: Patients scheduled for cardiac surgery were randomly allocated to receive either packed cells without buffy coat (PC, n = 306), fresh-filtered units (FF, n = 305), or stored-filtered units (SF, n = 303) when transfusion was indicated. We evaluated the periods of hospitalization and stay at the intensive care unit, and the occurrences of postoperative complications up to 60 days after surgery. The average hospital stay was 10.7 days, of which 3.2 days were in the intensive care unit, without significant differences between the groups. In the PC trial arm, 23.0% of the patients had infections versus 16.9% and 17.9% of the patients in the leukocyte-depleted trial arms (P=.13). Within 60 days, 45 patients had died, 24 patients in the PC trial arm (7.8%), versus 11 (3.6%) and 10 (3.3%) patients in the FF and SF trial arms, respectively (P=.015). CONCLUSIONS: In cardiac surgery patients, especially when more than three blood transfusions are required, leukocyte depletion by filtration results in a significant reduction of the postoperative mortality that can only partially be explained by the higher incidence of postoperative infections in the PC group.