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

ABSTRACT: INTRODUCTION: The increasing number of reports on the relation between transfusion of stored red blood cells (RBC) 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: 30 patients electively received one (N=8) or two (N=22) stored packed red blood cell units. Blood samples were drawn to analyze plasma levels of fHb levels, haptoglobin, and NO-consumption prior to transfusion, and 15minutes, 30minutes, 60minutes, 120minutes, and 24hours after transfusion. Differences were compared using Pearson Chi-square or Fisher's exact test for dichotomous variables, or independent sample t-test or Mann-Whitney-U-test for continuous data. Continuous, multiple time-point, data were analyzed using the repeated one-Way ANOVA or Kruskall-Wallis test. Correlations were analyzed using the 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 red blood cell 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 red blood cell 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. CONCLUSIONS: These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO-consumption in the recipient. This 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.