Effects of Blood Transfusion in Healthy Volunteers

The objective of this study is to assess effects of the storage of PRBC on endothelial function, inflammation and platelet activation in healthy volunteers.

The present study consists of two parts. During one phase of the study, 10 healthy human volunteers will donate a unit of blood, which will be leukoreduced and stored in Additive Solutions-1 (AS-1), and then transfused back to the subjects after 2 days of storage at 4º C in the MGH Blood Bank. The other part of the study consists in the collection of a unit of blood from the same volunteers, but which will be transfused back to the same subject after 40 days of storage. There will be a break of 2 week period in between these 2 study phases. The order of these 2 study parts will be randomized.

We hypothesize that old red blood cells stored under conventional conditions may trigger a complex, pro-inflammatory, pro-thrombotic and vasoconstriction response. We will compare the response to PRBC stored for 2 days with the response to PRBC stored for 40 days in the same healthy volunteers. We will monitor/measure the following markers/parameters:

1. Endothelium-mediated changes in vascular (arterial) tone
2. Tissue oxygen saturation will be continuously assessed during and after blood transfusion
3. Hemolysis as quantified by changes in plasma haptoglobin level, plasma free hemoglobin, LDH level, bilirubin level, iron level, ferritin, and transferrin
4. Changes of plasma and red blood cell levels of circulating nitrate, nitrite, RXNO, RNNO, NO-heme
5. Concentration of cytokines, such as IL-6, IL-8, IL-10, IL-12, TNF, IFN-γ
6. Activation of platelets through circulating P-selectin expression on platelets
7. Activation of inflammatory lipid mediators
8. Changes in gene expression profiling analyzing RNA microarray of circulating leukocytes