Objectives

The study had two objectives. For Aim 1: The primary hypothesis was that specific genetic and non-genetic donor factors, manufacturing factors, and recipient factors significantly predict RBC survival in people with hemoglobinopathies. RBC survival was defined by change in hemoglobin (thalassemia) or hemoglobin A (SCD) per day between transfusion visits. The predictors evaluated include donor (e.g., sex, age, race/ethnicity, smoking), component (e.g., storage duration, storage solution, irradiation), recipient data, and donor and recipient data obtained from a single nucleotide polymorphism (SNP) array (referred to as the Precision Transfusion Medicine Array [PTMA]). Secondary hypotheses included the association of RBC survival with a) recipient hemolysis pre-transfusion, b) hemoglobin increment (immediate post-pre hemoglobin), and c) hemolysis parameter increments immediately following transfusion.

The second Aim sought to measure markers of hemolysis and iron parameters from before to two hours after the transfusion in single RBC-unit transfusion events. Because the pathophysiology of the underlying disease and therefore the effects of hemolysis and iron handling may be different when comparing patients with thalassemia (ineffective erythropoiesis), SCD (chronic hemolysis), or hypoproliferative bone marrow (absent sink for iron in the bone marrow), the primary hypothesis of this aim was that the increase in iron post transfusion differs by disease. Secondary hypotheses included the relationship between storage age and increase in markers of hemolysis and that increased non transferrin bound iron (NTBI) or transferrin saturation following transfusion is associated with increased risk of clinical adverse effects (e.g., SCD complications).

Background

Patients with sickle cell disease (SCD) and thalassemia frequently require lifelong chronic red blood cell (RBC) transfusion therapy. In thalassemia, transfusion suppresses ineffective erythropoiesis, while in SCD transfusions reduce circulating sickle hemoglobin (HbS) to prevent complications caused by sickling of RBCs. However, transfusion effectiveness varies considerably between patients and between transfusion episodes in the same patient. This variability likely reflects the combined influence of donor characteristics, blood component manufacturing and storage conditions, and recipient clinical factors.

To better understand these issues, the RBC-IMPACT study was designed as a multicenter observational study within the NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-IV-P) program. The study links detailed donor, component, and recipient clinical data with genetic and laboratory measurements to evaluate how these factors influence RBC survival and iron metabolism following transfusion. By identifying predictors of transfusion effectiveness, the study aims to generate evidence that can optimize transfusion practices and improve safety for chronically transfused patients.

Participants

All transfused patients with sickle cell disease and thalassemia on simple chronic transfusion (or partial manual exchange transfusion) from hospitals affiliated with REDS-IV-P US sites (Aim #1)

Chronically transfused patients with sickle cell disease or thalassemia, and patients with pediatric oncology diagnoses with hypo-proliferative bone marrow receiving care at hospitals affiliated with REDS-IV-P US sites (Aim #2).

Inclusion Criteria (Aim #1):

• Well-characterized transfusion-dependent form of SCD or thalassemia (including Hemoglobin E-thalassemia and sickle-beta thalassemia) on chronic simple transfusion therapy or partial manual exchange
• On a regular simple RBC transfusion schedule, including partial manual exchange (i.e., 1-3 units scheduled every 2-6 weeks and on a minimum 6-month chronic transfusion trial; for partial manual exchange, the phlebotomy must be completed before the transfusion is started without a back and forth between rounds of phlebotomy and transfusion)
• Seen at any participating US REDS-IV-P study hospital

Exclusion Criteria (Aim #1):

• Institutionalization or imprisonment
• Foster care
• Weight <11 kg

Inclusion criteria (Aim #2):

• Either included in Aim #1 (consented patient with SCD or thalassemia) or patient with pediatric oncologic diagnosis under care in a pediatric hematology/oncology service with anemia due to chemotherapy or primary/secondary hypo-proliferative bone marrow requiring a RBC transfusion (including HSCT)
• Age ≤21 years old (many pediatric services include care of patients up to age 21, therefore the protocol will not limit by age but instead on whether they are seen in a pediatric service)
• Planned transfusion of RBC from an aliquot or unit from a single donor
• Seen at any participating US REDS-IV-P study hospital

Exclusion criteria (Aim #2):

• Institutionalization or imprisonment
• Foster care
• Current active auto-immune hemolytic anemia based on positive direct antiglobulin test (DAT) with laboratory evidence of hemolysis and increased transfusion requirement
• Microangiopathic hemolytic anemia
• Weight <18 kg

Disease Classification

Sickle Cell Disease, Thalassemia, Pediatric Cancer

Design

Observational Model, Cohort, Time Perspective, Prospective

The study included prospective data and blood sample collection combined with retrospective data acquisition using the REDS-IV-P V2V database. Participating hospitals and blood centers included Columbia University Irving Medical Center/Morgan Stanley Children’s Hospital of New York, Weill Cornell Medical Center/Komansky Children’s Hospital, New York Blood Center Enterprises (NYBCe), Boston Children’s Hospital, Froedtert & Medical College of Wisconsin/Children’s Hospital of Wisconsin, Versiti, University of California San Francisco, Benioff Children’s Hospital Oakland, and Vitalant in the US.

Conclusions

Analysis in development.