Transfusion of Stored Autologous Blood Does Not Alter Reactive Hyperemia Index in Healthy Volunteers

Abstract

Background Transfusion of human blood stored for over 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 following ischemia would be reduced after transfusion of packed erythrocytes stored for 40 days. Methods and results We conducted a cross-over 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 as compared to 3-day stored packed erythrocytes was unchanged. Plasma hemoglobin and bilirubin levels were higher after transfusion of 40-day than after 3-day stored packed erythrocytes (p = 0.02, [95% CI difference 10-114mg/l] and 0.001, [95% CI difference 0.6-1.5mg/dl], respectively). Plasma levels of potassium, Lactate dehydrogenase, haptoglobin, 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 levels of plasma nitrite.

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

“…We also exposed the forearm vasculature with a relatively larger transfusion exposure by infusing the blood directly into the brachial artery circulation. Prior studies in humans assessed vascular endothelial function by noninvasive measures of flow-mediated vasodilation after the systemic transfusion of 1 U of packed RBCs (PRBCs) (23,24,31). Transfusion studies in normal volunteers are limited by the amount of RBCs that can be infused.…”

“…Berra and colleagues (31) reported that 1-U transfusion of 40-day-aged red cells did not affect the reactive hyperemia index, a noninvasive measure of endothelial function, compared with transfusions of 3-day-aged red cells. In contrast, in a followup study the same group evaluated a single unit transfusion of autologous 40-daystored leukoreduced red cells into subjects with endothelial dysfunction and demonstrated increased post-transfusion levels of CFPHb, NO consumption, and pulmonary artery pressures estimated by Doppler echocardiography (23,31). Similarly, Neuman and colleagues (24) demonstrated that individuals with anemia receiving aged blood (.21 d) had evidence of endothelial dysfunction at 24 hours post-transfusion.…”

“…Several recent studies have assessed vascular endothelial function in normal human volunteers after transfusion of autologous blood (23,24,31). Berra and colleagues (31) reported that 1-U transfusion of 40-day-aged red cells did not affect the reactive hyperemia index, a noninvasive measure of endothelial function, compared with transfusions of 3-day-aged red cells.…”

Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

“…Following single-unit transfusion, other investigators found that intravascular Hb exposure is associated with concomitant elevation in plasma nitrite levels and NO depletion in humans following small volume blood transfusion (Berra et al 2012).…”

Purified and Recombinant Hemopexin: Protease Activity and Effect on Neutrophil Chemotaxis

“…This binding affinity is so high that Hx "steals" heme from hemoglobin (21). Heme and hemoglobin are synergistic with toll-like receptor (TLR) agonists a more conservative transfusion strategy (1)(2)(3)(4), studies suggesting that older stored blood is associated with higher morbidity than fresh blood (5)(6)(7)(8)(9), studies that older blood has higher levels of cell-free hemoglobin (10,11), in vitro studies in which hemoglobin and heme potentiate release of cytokines from macrophages (12)(13)(14), inTRODUCTiOn There has been increasing appreciation that cell-free plasma hemoglobin and secondarily released free heme may be toxic in critical care settings. Evidence for this concept comes from studies in which liberal transfusion is associated with equivalent or worse outcome than 2 Frank E Riley, perform amidolytic assay: H-D-IIe-ProArg-pNA⋅2HCl (S2288) that is sensitive to a broad spectrum of serine protease, and H-D-Phe-Pip-Arg-pNa⋅2HCl (S2238) that is sensitive to thrombin.…”