Effects of Transfusion of Older Red Blood Cells on Patients With Hemoglobinopathies
Epidemiologic studies suggest that older stored blood is associated with worse outcomes in certain hospitalized patients. Storage of red cells is associated with a storage lesion and the survival of transfused red cells decreases with increasing storage time, thus older blood is associated with an increased acute delivery of hemoglobin-iron to the reticuloendothelial system. The investigators have preliminary data in healthy human volunteers suggesting that delivery of a significant iron load to the reticuloendothelial system from aged red cells leads to the elaboration of a potentially toxic form of iron known as non-transferrin--bound iron. The investigators will extend these results by testing whether a similar effect is seen in chronically transfused patients with hemoglobinopathies. This patient population will also allow us to test whether iron- chelation therapy is beneficial in this setting. Finally, the investigators will also test whether washing or cryopreserving the red blood cells has any effect on this outcome. These findings may explain the immunomodulatory effects of older stored blood in patients and will help us develop safer transfusion products for patients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Harmful Effects of Transfusion of Older Stored Red Cells: Iron and Inflammation|
- Non-transferrin-bound iron [ Time Frame: 2 hours after transfusion ] [ Designated as safety issue: Yes ]
- transferrin saturation [ Time Frame: 2 hours following transfusion ] [ Designated as safety issue: No ]
- pro-inflammatory cytokines [ Time Frame: 2 hours after transfusion ] [ Designated as safety issue: No ]Interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 will be measured.
|Study Start Date:||February 2012|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
- Washed red blood cells
- Cryopreserved red blood cells
Below is a summary of the procedures to be performed on each donor participant followed by the procedures for each recipient participant:
Screening 2 tubes of blood will be drawn from a peripheral vein to perform a complete blood count and to perform blood bank testing (e.g. antibody screen, red cell phenotype). All donors who qualify based on criteria listed below, and have a red cell phenotype that matches a specific study patient will be recruited to perform 4 double red blood cell donations at the New York Blood Center over a 3 -year period based on the recipient's transfusion schedule. At least 112 days will be allotted between each blood donation (as per FDA regulations). Donors will have to pass the standard screening process (per FDA regulations) performed at the Blood Center, including standard infectious disease testing. Any donor failing screening due to infectious disease testing will be notified by trained counselors at the NY Blood Center and will be excluded from study participation. In addition, a new dedicated donor will replace any participant that drops out of the study, or becomes ineligible on subsequent attempts after successfully donating.
Study transfusions will be scheduled according to the patient's regular transfusion schedule such that one unit of the double red blood cell donation can be transfused "fresh" (i.e. prior to 14 days of storage) and the other unit can be transfused "old" (i.e. after 28 days of storage). The 8 transfusion events are listed below:
- "Fresh" transfusion while patient OFF chelation therapy
- "Old" transfusion while patient OFF chelation therapy
- "Fresh" transfusion while patient ON chelation therapy
- "Old" transfusion while patient ON chelation therapy
- "Fresh" washed transfusion while patient OFF chelation therapy
- "Old" washed transfusion while patient OFF chelation therapy
- "Fresh" transfusion while patient OFF chelation therapy
- Cryopreserved transfusion while patient OFF chelation therapy
For the 6 transfusions off chelation therapy, the patient will be asked to discontinue chelation therapy for 3 days prior to the scheduled transfusion. The washed and cryopreserved red cell units will be obtained per standard operating procedure from the New York Blood Center. Cryopreservation of one of the two donated double red blood cell units will be performed using Standard Operating Procedures at the New York Blood Center within 3 days of collection. Washing older stored RBC units and deglycerolizing cryopreserved red blood cell units will both be performed within 24 hours of transfusion, also by NYBC Standard Operating Procedures. Deglycerolization and washing of red blood cell units will each be performed using an automatic cell washing system (COBE 2991, CaridianBCT). All red cell units will be issued by the CUMC blood bank following standard operating procedures and a crossmatch.
The transfusion will take place in the Pediatric Hematology Clinic infusion center following standard procedures. An intravenous line will be placed and 4 tubes of blood will be drawn from the IV line prior to transfusion, immediately after transfusion, 1 hour after transfusion, and 2 hours after transfusion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01534676
|Contact: Eldad Hod, MDfirstname.lastname@example.org|
|Contact: Shruti Sharma, MSemail@example.com|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Eldad Hod, MD firstname.lastname@example.org|
|Contact: Shruti Sharma, MS email@example.com|
|Principal Investigator: Steven Spitalnik, MD|
|Sub-Investigator: Eldad Hod, MD|
|Sub-Investigator: Margaret Lee, MD|
|Principal Investigator:||Steven Spitalnik, MD||Columbia University|