Effects of Transfusion of Older Red Blood Cells on Patients With Hemoglobinopathies
| Status: | Recruiting |
|---|---|
| Conditions: | Anemia, Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 1 - 65 |
| Updated: | 7/11/2015 |
| Start Date: | February 2012 |
| Contact: | Eldad Hod, MD |
| Email: | eh2217@columbia.edu |
| Phone: | 212-342-5648 |
Harmful Effects of Transfusion of Older Stored Red Cells: Iron and Inflammation
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.
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.
Below is a summary of the procedures to be performed on each donor participant followed by
the procedures for each recipient participant:
Donor participants:
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.
Recipient participants:
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:
1. "Fresh" transfusion while patient OFF chelation therapy
2. "Old" transfusion while patient OFF chelation therapy
3. "Fresh" transfusion while patient ON chelation therapy
4. "Old" transfusion while patient ON chelation therapy
5. "Fresh" washed transfusion while patient OFF chelation therapy
6. "Old" washed transfusion while patient OFF chelation therapy
7. "Fresh" transfusion while patient OFF chelation therapy
8. 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.
the procedures for each recipient participant:
Donor participants:
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.
Recipient participants:
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:
1. "Fresh" transfusion while patient OFF chelation therapy
2. "Old" transfusion while patient OFF chelation therapy
3. "Fresh" transfusion while patient ON chelation therapy
4. "Old" transfusion while patient ON chelation therapy
5. "Fresh" washed transfusion while patient OFF chelation therapy
6. "Old" washed transfusion while patient OFF chelation therapy
7. "Fresh" transfusion while patient OFF chelation therapy
8. 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.
Inclusion Criteria (Recipient):
- specific, well-characterized hemoglobinopathy
- chronic simple transfusion therapy (transfusion episodes < 6 weeks apart in
frequency)
- chronic iron chelation therapy
- not pregnant by self-report and not planning pregnancy
- age > 1 year old
Exclusion Criteria (Recipient):
- clinically unstable
- treatment for mental illness
- imprisonment
- institutionalization
Inclusion Criteria (Donor):
- 21-65 years of age
- male weight > 130 lbs, female weight > 150 lbs
- male height > 5'1", female height > 5'5"
- hemoglobin > 15.0 g/dL
- reasonably certain of intention to stay in New York City metropolitan area for study
duration
- previously tolerated red blood cell donation
Exclusion Criteria (Donor):
- ineligible for donation based on New York Blood Center blood donor screening
questionnaire
- systolic blood pressure < 90 or > 180 mm Hg, diastolic blood pressure < 50 or > 100
mm Hg
- heart rate < 50 or > 100
- temperature > 99.5 F prior to donation
- positive by standard infectious disease testing performed on blood donors
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