Transfusion of stored autologous blood does not alter reactive hyperemia index in healthy volunteers

Abstract

Background: Transfusion of human blood stored for more than 2 weeks is associated with increased mortality and morbidity. During storage, packed erythrocytes progressively release hemoglobin, which avidly binds nitric oxide. We hypothesized that the nitric oxide mediated hyperemic response after ischemia would be reduced after transfusion of packed erythrocytes stored for 40 days.

Methods and results: We conducted a crossover randomized interventional study, enrolling 10 healthy adults. Nine volunteers completed the study. Each volunteer received one unit of 40-day and one of 3-day stored autologous leukoreduced packed erythrocytes, on different study days according to a randomization scheme. Blood withdrawal and reactive hyperemia index measurements were performed before and 10 min, 1 h, 2 h, and 4 h after transfusion. The reactive hyperemia index during the first 4 h after transfusion of 40-day compared with 3-day stored packed erythrocytes was unchanged. Plasma hemoglobin and bilirubin concentrations were higher after transfusion of 40-day than after 3-day stored packed erythrocytes (P = 0.02, [95% CI difference 10-114 mg/l] and 0.001, [95% CI difference 0.6-1.5 mg/dl], respectively). Plasma concentrations of potassium, lactate dehydrogenase, haptoglobin, and cytokines, as well as blood pressure, did not differ between the two transfusions and remained within the normal range. Plasma nitrite concentrations increased after transfusion of 40-day stored packed erythrocytes, but not after transfusion of 3-day stored packed erythrocytes (P = 0.01, [95% CI difference 0.446-0.66 μM]).

Conclusions: Transfusion of autologous packed erythrocytes stored for 40 days is associated with increased hemolysis, an unchanged reactive hyperemia index, and increased concentrations of plasma nitrite.

Trial registration: ClinicalTrials.gov NCT00991341.

Figures

Figure 1. Study protocol and randomization

Ten healthy volunteers were enrolled and received one unit of 3DS and one of 40DS packed erythrocytes in random order. One subject was excluded, because of anemia and did not meet criteria for the second blood donation.

Figure 2. Examples of peripheral arterial tonometry (PAT) measurements

PAT recording in one subject 4 h after transfusion of either (A) 3DS or (B) 40DS packed erythrocytes. The brachial blood pressure cuff was deflated to elicit the hyperemic response after 5 min of inflation to 250 mmHg (arrows).

Figure 3. Effects of transfusing 3 and 40 day stored autologous packed erythrocytes

Measurements of in vivo (A) systolic blood pressure, (B) reactive hyperemia (RH) index, (C) plasma hemoglobin, (D) haptoglobin, (E) leukocytes (WBC), and (F) nitrite before and after transfusions of either 40DS (blue) or 3DS (red). All data are represented as Mean ± SE * p < 0.05 by two-way ANOVA for repeated measures analysis; log-transformed data were used for statistical analysis of RHI and Nitrite †p < 0.05 for post-hoc within time-point comparison of the two treatments ‡, §p < 0.05 for post-hoc comparison with pretransfusion values (40DS and 3DS blood, respectively)