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Open Access Highly Accessed Research

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

Iris C Vermeulen Windsant12, Norbert CJ de Wit3, Jonas TC Sertorio4, Erik AM Beckers5, Jose E Tanus-Santos4, Michael J Jacobs1678 and Wim A Buurman12*

Author Affiliations

1 Department of Surgery, Maastricht University Medical Center, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands

2 Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University Medical Center, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands

3 Central Diagnostic Laboratory, Maastricht University Medical Center, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands

4 Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Av. Bandeirantes, 3900 Ribeirão Preto, São Paolo, Brazil

5 Department of Hematology, Maastricht University Medical Center, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands

6 Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands

7 European Vascular Center Maastricht-Aachen, the Netherlands-Germany University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

8 Department of Vascular Surgery, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

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Critical Care 2012, 16:R95  doi:10.1186/cc11359


See related commentary by Finney, http://ccforum.com/content/16/4/141

Published: 25 May 2012

Abstract

Introduction

The increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied.

Methods

Thirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation.

Results

Storage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations.

Conclusion

These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.