Microparticles in Stored RBC as Potential Mediators of Transfusion Complications
INTRODUCTION. Cell-derived microparticles (MP) are released in cell activation, apoptosis and other processes. MP derived from red cells (RMP) are known to be released from stored packed red blood cells (PRBC), and their number increases with storage time. This constitutes one aspect of the storage lesion. Adverse transfusion events are known to increase with time of PRBC storage. The explanation for this is not known.
HYPOTHESIS. Based on their findings and those of others, the investigators propose to test the hypothesis that MP in stored PRBC contribute to adverse effects of transfusion. Specifically, MP in stored blood: (1) increase procoagulant activity, expression of pro-inflammatory mediators, immune suppression, and endothelial disturbance; and (2) increase the risk of transfusion and post-operative complications in patients undergoing coronary artery bypass grafting (CABG).
AIMS & PROCEDURES. The aim of this study is to assess the clinical significance of MPs in PRBC-related transfusion complications utilizing washed PRBC. Packed red blood cells (PRBC) will be washed at the blood bank to obtain MP depleted PRBC (PRBC-MP). A total of 500 patients undergoing CABG will be initially randomized to 2 groups: one to receive PRBC-MP, and the other conventional PRBC (PRBC+MP). Using a panel of lab tests/biomarkers selected for high sensitivity the investigators will compare the 2 groups with respect to subclinical physiologic host responses including (i) endothelial disturbances, (ii) inflammatory, and (iii) procoagulant responses. In addition, clinically evident transfusion complications and short term (<=30 days) surgical complications will be assessed and compared. Patients who are randomized but end up not requiring transfusion at surgery will serve as controls. Laboratory and clinical results will also be evaluated to elucidate which tests are significantly associated with clinically adverse effects.
SIGNIFICANCE. This study will shed new light on the biochemical and clinical effects of transfusion of MP. The findings of this investigation could significantly improve transfusion practice and safety.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Microparticles in Stored Red Blood Cells (RBC) as Potential Mediators of Transfusion Complications (II): Clinical Study|
- In hospital Mortality [ Time Frame: within 30 days after surgery ] [ Designated as safety issue: Yes ]
- One-year Mortality [ Time Frame: within one year after surgery ] [ Designated as safety issue: Yes ]
- Serious Adverse Events (sepsis, respiratory failure, multi-organ failure, anaphylactic shock, transfusion-related acute lung injury, MI, stroke, cardiac arrest) [ Time Frame: within 30 days after surgery ] [ Designated as safety issue: Yes ]
- Non-serious adverse events [ Time Frame: within 30 days after surgery ] [ Designated as safety issue: Yes ]
- cell-derived microparticles [ Time Frame: presurgery, day1, day3, and day7 post-surgery ] [ Designated as safety issue: No ]Cell-derived microparticles include red cell microparticles, platelet microparticles, leukocyte microparticles, endothelial microparticles
|Study Start Date:||July 2010|
|Study Completion Date:||May 2015|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Transfusion with washed RBC
Subject assigned to this arm will be transfused with washed RBC
Biological: Washed RBC
There is no pre-set dosage, frequency and duration for transfusion with washed RBC. It all depends on the conditions of patients during and after surgery. As circumstances arise, the physician will request needed washed RBC for the subject.
Other Name: Washed packed cells
Active Comparator: Transfusion with unwashed RBC
Subjects assigned to this arm will be transfused with unwashed RBC
Biological: Unwashed RBC
There is no pre-set dosage, frequency and duration for transfusion with unwashed RBC. It all depends on the conditions of patients during and after surgery. As circumstances arise, the physician will request needed unwashed RBC for the subject.
Other Name: Unwashed packed cells
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01185600
|United States, Florida|
|Jackson Memorial Hospital|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Wenche Jy, PhD||University of Miami|