Leo van de Watering
Leiden University Medical Center
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Featured researches published by Leo van de Watering.
Circulation | 1998
Leo van de Watering; Jo Hermans; J.G.A. Houbiers; Pieter J. van den Broek; Hens Bouter; Fred Boer; Mark S. Harvey; Hans A. Huysmans; Anneke Brand
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.
The New England Journal of Medicine | 2015
Jacques Lacroix; Paul C. Hébert; Dean Fergusson; Alan Tinmouth; Deborah J. Cook; John Marshall; Lucy Clayton; Lauralyn McIntyre; Jeannie Callum; Alexis F. Turgeon; Morris A. Blajchman; Timothy S. Walsh; Simon J. Stanworth; Helen Campbell; Gilles Capellier; Pierre Tiberghien; Laurent Bardiaux; Leo van de Watering; Nardo J.M. van der Meer; Elham Sabri; Abstr Act
BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).
Transfusion | 2006
Leo van de Watering; Jos Lorinser; Michel I. M. Versteegh; Rudi Westendord; Anneke Brand
BACKGROUND: In different centers for cardiothoracic surgery throughout the world, different policies are followed concerning the maximum storage time of to‐be‐transfused red blood cells (RBCs). The aim in this study was to investigate the possible role of the storage time of RBC transfusions on the outcome of coronary artery bypass graft (CABG) surgery patients.
BMJ | 2004
Joost A. van Hilten; Leo van de Watering; J. Hajo van Bockel; Cornelis J. H. van de Velde; Job Kievit; Ronald Brand; Wilbert B. van den Hout; Robert H. Geelkerken; Rudi M H Roumen; Ronald M J Wesselink; Ankie W. M. M. Koopman-van Gemert; Jan Koning; Anneke Brand
Abstract Objective To compare postoperative complications in patients undergoing major surgery who received non-filtered or filtered red blood cell transfusions. Design Prospective, randomised, double blinded trial. Setting 19 hospitals throughout the Netherlands (three university; 10 clinical; six general). Participants 1051 evaluable patients: 79 patients with ruptured aneurysm, 412 patients undergoing elective surgery for aneurysm, and 560 undergoing gastrointestinal surgery. Interventions The non-filtered products had the buffy coat removed and were plasma reduced. The filtered products had the buffy coat removed, were plasma reduced, and filtered before storage to remove leucocytes. Main outcome measures Mortality and duration of stay in intensive care. Secondary end points were occurrence of multi-organ failure, infections, and length of hospital stay. Results No significant differences were found in mortality (odds ratio for filtered v non-filtered 0.80, 95% confidence interval 0.53 to 1.21) and in mean stay in intensive care (- 0.4 day, - 1.6 to 0.6 day). In the filtered group the mean length of hospital stay was 2.4 days shorter (- 4.8 to 0.0 day; P = 0.050) and the incidence of multi-organ failure was 30% lower (odds ratio 0.70, 0.49 to 1.00; P = 0.050). There were no differences in rates of infection (0.98, 0.73 to 1.32). Conclusion The use of filtered transfusions in some types of major surgery may reduce the length of hospital stay and the incidence of postoperative multi-organ failure.
Transfusion | 2003
Leo van de Watering; Jo Hermans; Marian Witvliet; Michel I. M. Versteegh; Anneke Brand
BACKGROUND: WBC reduction of all blood components is being introduced in many countries. Prevention of immunologic side effects of transfusions is part of the motivation. To compare the immunogenicity of before‐ or after‐storage WBC‐reduced RBCs with RBCs without buffy coat, a randomized clinical trial was performed.
The Lancet | 2016
Meghan Delaney; Silvano Wendel; Rachel S. Bercovitz; Joan Cid; Claudia S. Cohn; Nancy M. Dunbar; Torunn O. Apelseth; Mark Popovsky; Simon J. Stanworth; Alan Tinmouth; Leo van de Watering; Jonathan H. Waters; Mark H. Yazer; Alyssa Ziman
Blood transfusion is one of the most common procedures in patients in hospital so it is imperative that clinicians are knowledgeable about appropriate blood product administration, as well as the signs, symptoms, and management of transfusion reactions. In this Review, we, an international panel, provide a synopsis of the pathophysiology, treatment, and management of each diagnostic category of transfusion reaction using evidence-based recommendations whenever available.
Transfusion | 2010
Rutger A. Middelburg; Leo van de Watering; Johanna G. van der Bom
C onfounding by indication is a serious potential problem in clinical observational research and can easily lead to unjustified conclusions, as has also been described previously. In transfusion medicine such a conclusion could be “blood transfusions kill,” since patients receiving more transfusions are almost invariably more likely to die. Even though most would agree that blood transfusions save lives, this erroneous conclusion did find its way into the literature. Although this example might seem overly obvious, confounding by indication can be indirect and much more subtle and difficult to detect. It is therefore of the utmost importance to thoroughly understand the nature of confounding by indication, to be able to recognize it and avoid unjustified conclusions. We introduce the problem of confounding by indication with examples from clinical transfusion research and provide a general explanation to help identify this form of bias in the literature and in the every day clinical research settings (for guidelines on detection and handling, see Table 1).
Critical Care Medicine | 2010
Yavuz M. Bilgin; Leo van de Watering; Michel I. M. Versteegh; Marinus H. J. van Oers; Anneke Brand
Objective: To investigate whether the higher prevalence of postoperative complications in cardiac surgery after transfusion of leukocyte-containing red blood cells can be related to inflammatory mediators. Design: Analysis of inflammatory markers interleukin-6, interleukin-10, interleukin-12, and procalcitonin in patients participating in a randomized trial comparing leukocyte-depleted with leukocyte-containing, buffy-coat-depleted red blood cells. Setting: Two university-affiliated hospitals in the Netherlands. Subjects: A total of 346 patients undergoing cardiac valve surgery with a complete series of pre- and postoperative blood samples. Measurements and Main Results: There were no differences in the cytokines and procalcitonin concentrations between both study arms when the patients arrived in the intensive care unit. In subgroups, patients who received zero to three red blood cell transfusions showed similar cytokine concentrations in both study arms, whereas patients with ≥4 red blood cell transfusions had significantly higher interleukin-6 concentrations in the leukocyte-containing, buffy-coat-depleted red blood cell group. Patients who developed postoperative infections and multiple organ dysfunction syndrome showed, respectively, increased concentrations of interleukin-6 and interleukin-12 in the leukocyte-containing, buffy-coat-depleted, red blood cell group. The interaction tests in these subgroups showed significantly different reaction patterns in the leukocyte-containing, buffy-coat-depleted red blood cell group compared with leukocyte-depleted red blood cell group for interleukin-6 and interleukin-12. Multivariate analysis showed a high interleukin-6 concentration with multiple organ dysfunction syndrome and both high interleukin-6 and interleukin-10 concentrations with hospital mortality. Conclusions: Allogeneic leukocyte-containing blood transfusions compared with leukocyte-depleted blood transfusions induce dose-dependent significantly higher concentrations of proinflammatory mediators in the immediate postoperative period after cardiac surgery. High concentrations of interleukin-6 are strong predictors for development of multiple organ dysfunction syndrome, whereas both interleukin-6 and interleukin-10 are associated with hospital mortality. These findings suggest that leukocyte-containing red blood cells interfere with the balance between postoperative proinflammatory response, which may further affect the development of complications after cardiac surgery.
Transfusion | 2011
Leo van de Watering
P ossible adverse effects related to transfusing “old” red blood cells (RBCs) have been investigated extensively. As the ongoing randomized controlled trials (RCTs) on the effects of RBC storage may still take years to report their results, current RBC storage and transfusion policies will have to be based on the currently available, mostly observational, literature. These observational studies are valuable, as they may rationally direct the formulation of sound hypotheses. However, the results from these observational studies on storage time are conflicting, making it impossible to reach a consensus. This is not solely based on the limitations of the observational design of the studies. On close examination, a large number of the published observational studies have failed to evade pitfalls in performing RBC storage research. Here, several aspects of study design and analyses are discussed that illustrate pitfalls that may result in seriously biased comparisons and unsupported conclusions. Most studies that rise to the level of broad consideration and even discussion by the lay public are those showing strong association between the age of RBCs and a clinical endpoint. Investigations that fail to demonstrate such associations generally have less fanfare associated with them. The pitfalls discussed herein apply both to the former and to the latter, “negative findings,” studies. The most important pitfalls are identified, the introduced bias is shown, and possible ways to reduce bias are discussed. By drawing attention to these pitfalls hopefully future authors may evade them, reviewers and editors may more easily recognize biased comparisons, and physicians and blood bankers may more carefully identify the studies on which to base a sound RBC storage and transfusion policy, reaching an optimal situation on safety and availability of RBC transfusions.
Transfusion | 2012
Rutger A. Middelburg; Barbara Borkent; Mart Jansen; Leo van de Watering; Johanna C. Wiersum-Osselton; Martin R. Schipperus; Erik A.M. Beckers; Ernest Briët; Johanna G. van der Bom
BACKGROUND: Besides white blood cell antibodies in plasma‐rich products, another cause of transfusion‐related acute lung injury (TRALI) could be release of biologically active substances during storage of cellular blood products. We aimed to investigate the association of storage time and risk of TRALI for different product types.