Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure

Abstract

Rationale: Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction.Objectives: We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure.Methods: Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide.Measurements and Main Results: The age of volunteers was 41 6 4 years (mean 6 SEM), and their body mass index was 33.4 6 1.3 kg/ m 2 . Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 6 2 to 23 6 2 mm Hg; P , 0.05) but did not change after transfusing 3-day blood (17 6 2 to 18 6 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 6 2 to 12 6 1 mm Hg; P , 0.05).Conclusions: Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. Clinical trial registered with www.clinicaltrials.gov (NCT 01529502).

Iron accelerates hemoglobin oxidation increasing mortality in vascular diseased guinea pigs following transfusion of stored blood

“…This hemodynamic response in HFSD guinea pigs was associated with Hb-induced expression of inactive eNOS (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.93577DS1). These characteristics mimic a frequent cardiovascular comorbidity found in patients undergoing blood transfusion (26).…”

“…The vulnerability of mice (24,25,32), lambs (15), and patients (26) with endothelial dysfunction to the pathophysiological effects of Hb and RBC transfusion has been established by Zapol and colleagues. This group has also convincingly demonstrated that maximally stored RBCs (42-day equivalent) caused a poor resuscitation response in a mouse model of shock (24,25) and a significant increase in pulmonary arterial pressure in obese volunteers (26).…”

Intravascular hemolysis and the pathophysiology of sickle cell disease

“…In animals, inducing intravascular hemolysis or infusing hemoglobin or hemolysate can produce experimental NO resistance (86)(87)(88)(89). This effect is attributable to hemoglobin and NO scavenging, as it can be blocked by oxidization of hemoglobin to methemoglobin with inhaled NO gas or by binding and clearance of hemoglobin with haptoglobin (86,(89)(90)(91). Acute intravascular hemolysis induced by hypotonic water infusion in mice inhibits NO signaling and causes inflammation, an effect phenocopied by acute NO inhibition using chemical NO scavengers and reversed by an NO donor and haptoglobin (92).…”

“…Infusing aged stored blood into rodents (89,93,94) and humans (90,95) causes intravascular hemolysis, pulmonary and systemic hypertension, and vascular endothelial dysfunction (due to impaired NO signaling) that can be blocked by haptoglobin (96). These effects are not always observed in models or patient populations in which hemolysis is not as severe, the dose of transfused red cells is not large, and the existing compensatory reserves of haptoglobin, hemopexin, and catalytic antioxidants are not as chronically depleted as in SCD.…”

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

“…However, in these studies the mean ages of older blood were only 22 and 28.3 days, respectively, and very few units of blood were transfused at the extreme limits of FDA-approved storage of 42 days (16)(17)(18). Thus, although transfusion of blood may increase risk (12,13,15,19), whether this risk is compounded by storage age, especially at the limits of storage and in the setting of larger transfusion volumes, remains unclear (20)(21)(22)(23)(24).…”