Background:
Sickle cell disease (SCD) is an inherited disorder of the blood. SCD causes red blood cells (RBCs) to die early. This can lead to a shortage of healthy cells. SCD and other blood disorders can be managed with drugs or cured with a bone marrow transplant. Researchers want to know how long RBCs survive in people with SCD and other blood disorders before and after treatment compared to those who had a bone marrow transplant.
Objective:
To learn how long RBCs survive in the body in people with SCD and other blood disorders compared to those whose disease was cured with a bone marrow transplant.
Eligibility:
People aged 18 years or older with SCD or another inherited blood disorder. People whose SCD or blood disorder was cured with a bone marrow transplant are also needed.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests.
Participants will have about 7 tablespoons of blood drawn. In the lab, this blood will be mixed with a vitamin called biotin. Biotin sticks to the outside of RBCs. This process is called "biotin labeling of RBCs." The next day, the participant s own biotin-labeled RBCs will be returned to their bloodstream.
Participants will return regularly to have smaller blood samples (about 2 teaspoons) drawn. These samples will be tested to detect the percentage of cells that have biotin labels. These visits may be every 2 weeks, 4 weeks, or some other interval. Participants will continue this schedule for up to 20 weeks or until biotin can no longer be detected....
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18 years or greater with confirmed diagnosis of SCD (all genotypes), thalassemia (beta and/or alpha), or other inherited hemoglobinopathy not otherwise specified.
Be at steady state for their underlying disease (e.g. SCD or thalassemia) or post-bone marrow transplantation status, as evidenced by medical history.
Consumption of biotin supplements or raw eggs within the last 30 days.
Blood loss within the previous 8 weeks (>540 mL).
Red cell transfusion for their underlying SCD and/or thalassemia within the last 3 months.
Patients on hemodialysis, due to possibility of early removal of biotinylated RBCs.
Single group
Biotin-labeled red blood cells
Biological/VaccineCellular Product (patient's own red blood cells washed in Biotin and infused back to patient)
To determine and compare red blood cell survival, by virtue of the mean number of days of detectable biotin-labeled RBCs, in participants with SCD and/or other hemoglobinopathies.
Enumeration of biotin-labeled RBCS (BioRBCs) will be performed by flow cytometry. F-cell and/or S-cell measurement will be done by flow cytometry. BioRBCs will be isolated from post-infusion blood samples using flow cytometry separation. The collected BioRBCs and the whole blood fraction will be analyzed by high performance liquid chromatography (HPLC) for hemoglobin content.
Validate the association of RBC survival with known markers of increased survival.
We will measure the relationship of RBC survival to hematologic parameters known to be associated with survival, specifically hemolysis markers (e.g. absolute reticulocyte count, lactate dehydrogenase, total bilirubin, and aspartate aminotransferase), hemoglobin F or hemoglobin A percentage, and alpha globin gene mutation status obtained at baseline and during scheduled lab draws (except for alpha globin gene mutation analysis which is only done at baseline).
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National Heart, Lung, and Blood Institute (NHLBI)
Lead sponsor
Children's National Research Institute
Collaborator
