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Randomized Controlled Trial
. 2015 May 1;10(5):e0122655.
doi: 10.1371/journal.pone.0122655. eCollection 2015.

Plasma Free Hemoglobin and Microcirculatory Response to Fresh or Old Blood Transfusions in Sepsis

Free PMC article
Randomized Controlled Trial

Plasma Free Hemoglobin and Microcirculatory Response to Fresh or Old Blood Transfusions in Sepsis

Elisa Damiani et al. PLoS One. .
Free PMC article


Background: Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.

Methods: This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.

Results: Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098-0.219] mg/mL to 0.238 [0.163-0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).

Conclusions: Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.

Trial registration: NCT01584999.

Conflict of interest statement

Competing Interests: CI is the inventor of sidestream dark field imaging technology and holds shares in MicroVision Medical and was a consultant for this company more than four years ago but has had no further contact with the company since then. He has no other competing interests in this field other than his commitment to promoting the importance of the microcirculation during patient care; and there are no other relationships or activities that could appear to have influenced the submitted work. The other authors have no competing interests to declare.


Fig 1
Fig 1. Changes in plasma free haemoglobin after blood transfusion in the two groups.
(A) Individual changes in plasma free haemoglobin after blood transfusion in the two groups; **p<0.01, Wilcoxon matched-pair signed rank test. (B) Delta values (after-before transfusion) of plasma free haemoglobin in the two groups. *p<0.05, Mann-Whitney U test. Open circles indicate patients in the fresh RBC group, full circles patients in the old RBC group.
Fig 2
Fig 2. Correlation analysis between the change in plasma fHb (X axis) and changes in: (A) total small vessel density, (B) perfused vessel density, (C) De Backer score, (D) tissue haemoglobin index, (E) tissue oxygen saturation (Y axis).

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