Non-Identical Blood Type Transfusions for Patient Outcomes

(UD Trial)

Recruiting in Hamilton (>99 mi)

Overseen By Nancy Heddle

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Disqualifiers: Blood group O, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether giving patients blood that exactly matches their own type can reduce complications and deaths. It focuses on patients who need transfusions and are at higher risk of problems when given non-matching blood. The goal is to prevent harmful immune reactions by using matching blood types.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications.

Is it safe to receive a blood transfusion with a non-identical blood type?

Blood transfusions, including those with red blood cells, can have risks such as adverse reactions and complications. Studies have shown that factors like storage duration and irradiation can increase these risks, and transfusions can lead to serious reactions like hemolysis (destruction of red blood cells). While transfusions are common, they are associated with various adverse effects, especially in specific populations like newborns and patients with heart conditions. ^{1 2 3 4 5}

How is the treatment of non-identical blood type transfusions unique compared to other treatments?

Non-identical blood type transfusions are unique because they involve transfusing blood that doesn't match the recipient's blood type exactly, which is not standard practice. This approach may focus on matching other blood components or antigens to improve outcomes, unlike traditional transfusions that prioritize exact blood type matching. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Non-Identical Blood Type Transfusions for Patient Outcomes?

Research shows that red blood cell (RBC) transfusion therapy has been effective in reducing mortality and morbidity in patients with cancer who receive multiple transfusions. This suggests that RBC transfusions, even with non-identical blood types, could potentially improve patient outcomes. ^{6 10 11 12 13}

Who Is on the Research Team?

Donald Arnold

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Myelodysplastic Syndrome (MDS) who don't have leukemia. They must need regular blood transfusions every 6 weeks or less, be stable according to their doctor's assessment, and not require special blood products due to reactions. People with blood group O or those unable to consent are excluded.

Inclusion Criteria

I have been diagnosed with MDS without leukemia, classified as low or intermediate-1 risk.

Blood group A, B, or AB

I need blood transfusions of 2 units at least every 6 weeks.

Exclusion Criteria

I am unable to understand and give consent for treatment.

My blood type is O.

I need special blood products due to reactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transfusion Episode 1

Participants receive an ABO identical product during the first transfusion episode

1 day

1 visit (in-person)

Transfusion Episode 2

Participants receive an ABO non-identical product during the second transfusion episode

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in biomarkers of inflammation and other safety parameters after transfusion

12-24 hours

What Are the Treatments Tested in This Trial?

Interventions

• RBC transfusion

Trial Overview The study is examining if receiving Red Blood Cell (RBC) transfusions that aren't a perfect match for the patient's ABO blood type affects their health outcomes. It follows earlier research suggesting non-identical RBCs might increase in-hospital death risk.

How Is the Trial Designed?

Group I: ABO non-identical transfusion Experimental Treatment 1 Intervention

All study patients will participate in the study for two consecutive transfusion episodes (a transfusion episode is defined as a clinic visit where 2 RBC units are transfused) and will receive an ABO identical product at one transfusion episode and an ABO non-identical product for the other episode. Randomization will dictate the order of the transfusion. The number of RBCs given for each study transfusion episode will be identical 2 RBC units.

Group II: ABO identical transfusion Active Control 1 Intervention

All study patients will participate in the study for two consecutive transfusion episodes (a transfusion episode is defined as a clinic visit where 2 RBC units are transfused) and will receive an ABO identical product at one transfusion episode and an ABO non-identical product for the other episode. Randomization will dictate the order of the transfusion. The number of RBCs given for each study transfusion episode will be identical 2 RBC units.

RBC transfusion is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Red Blood Cell transfusion for:

• Anemia
• Blood loss
• Surgical procedures

Approved in United States as RBC transfusion for:

• Anemia
• Blood loss
• Surgical procedures
• Trauma

Approved in Canada as Red Blood Cell transfusion for:

• Anemia
• Blood loss
• Surgical procedures

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

CBS

Collaborator

Trials

2

Recruited

280+

Published Research Related to This Trial

A study analyzing 732 cases of red blood cell alloimmunization in patients with oncological malignancies found that transfusion significantly increases the risk of developing antibodies against Rh blood group antigens, particularly the E antigen.

To minimize the risk of alloimmunization in these high-risk patients, the study recommends implementing a policy for extended RBC phenotyping and providing antigen-matched blood, especially for the E antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy. Fang, W., Pang, C., Zhang, F., et al.[2023]

In a study of 10,069 critically ill patients across 730 ICUs worldwide, 26.3% received red blood cell (RBC) transfusions, with significant variations in practice based on geographic regions.

While transfusions were associated with higher hospital mortality rates overall (30.0% for transfused vs. 19.6% for non-transfused), they showed a slightly lower relative risk of in-hospital death in the most severely ill patients, suggesting that transfusion decisions should consider the severity of illness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Worldwide audit of blood transfusion practice in critically ill patients. Vincent, JL., Jaschinski, U., Wittebole, X., et al.[2018]

In a study of 6124 cardiac surgical patients, receiving 1-2 units of leukocyte-depleted red blood cells (RBCs) did not increase the risk of long-term mortality compared to those who received no transfusion, with a hazard ratio of 1.00, indicating no significant difference.

Preoperative anemia was not found to be a risk factor for increased postoperative mortality, even among patients who received transfusions, suggesting that transfusion practices may not need to change based on anemia status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No Significant Association Between the Transfusion of Small Volumes of Leukocyte-Depleted Red Blood Cells and Mortality Over 7 Years of Follow-up in Patients Undergoing Cardiac Surgery: A Propensity Score Matched Analysis. Koster, A., Zittermann, A., Börgermann, J., et al.[2019]

A study analyzing data from 275,874 patients across 21 hospitals found that admission hemoglobin levels are the strongest predictor of red blood cell transfusion events, significantly influencing transfusion decisions within the first 24 hours and throughout hospitalization.

The predictive model developed showed high accuracy (C-statistic of 0.928 for 24-hour transfusion prediction), indicating that while patient comorbidities and severity of illness are considered, they have a smaller impact on transfusion decisions compared to hemoglobin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting red blood cell transfusion in hospitalized patients: role of hemoglobin level, comorbidities, and illness severity. Roubinian, NH., Murphy, EL., Swain, BE., et al.[2021]

In a study of 555 patients undergoing hematopoietic stem cell transplantation (HSCT), the age of red blood cell (RBC) units transfused (old vs. new) did not affect clinical outcomes such as nonrelapse mortality or organ-specific toxicity.

Patients requiring more RBC transfusions experienced greater toxicity and longer hospital stays, but the study did not establish a direct link between RBC transfusion and increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Storage time of transfused red blood cells and impact on clinical outcomes in hematopoietic stem cell transplantation. Kekre, N., Chou, A., Tokessey, M., et al.[2011]

In a study involving four dogs that experienced acute hemolytic transfusion reactions, two dogs died and one was euthanized due to complications likely caused by improper storage of red blood cell (RBC) products.

The investigation revealed that RBC units from two blood banks were hemolyzed after being stored incorrectly, highlighting the importance of proper storage and monitoring of blood products to prevent life-threatening transfusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro lysis and acute transfusion reactions with hemolysis caused by inappropriate storage of canine red blood cell products. Patterson, J., Rousseau, A., Kessler, RJ., et al.[2021]

Nonleukoreduced red blood cell (RBC) preparations contain a significant number of activated platelets and can induce the formation of platelet-white blood cell aggregates, which may contribute to adverse clinical outcomes in patients with acute cardiovascular disease.

In contrast, leukoreduced RBCs have very few platelets and induce much less aggregation, suggesting that the presence of activated platelets in nonleukoreduced RBCs is a key factor in the negative effects observed with transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of platelet white blood cell (WBC) aggregate formation by platelets and WBCs in red blood cell units. Keating, FK., Fung, MK., Schneider, DJ.[2008]

In a study analyzing 149,052 units of transfused red blood cells (RBCs) over 5.5 years, irradiated RBCs were found to significantly increase the frequency of non-allergic transfusion reactions, with an odds ratio of 1.89.

Prolonged storage of irradiated RBCs was specifically linked to a higher incidence of these non-allergic reactions, suggesting that both irradiation and storage duration may impact the safety of RBC transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiation and prolonged storage of red cells are associated with increased adverse events. Chen, J., Biller, E., Losos, M., et al.[2019]

This systematic review aims to clarify the incidence and types of adverse effects associated with small-volume red blood cell (RBC) transfusions (10-20 mL/kg) in neonates, addressing a significant gap in current research.

RBC transfusions in neonates are linked to serious morbidities such as chronic lung disease and retinopathy of prematurity, highlighting the need for a better understanding of the risks versus benefits in transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of small-volume red blood cell transfusions in the neonatal population. Keir, A., Pal, S., Trivella, M., et al.[2021]

In a study of 108 patients who underwent isolated coronary artery bypass grafting (CABG), those who received perioperative red blood cell (RBC) transfusions had significantly higher rates of adverse outcomes, including prolonged ventilatory support (21.8% vs. 0%), cardiac morbidity (14.1% vs. 0%), renal morbidity (28.2% vs. 3.3%), and serious infections (20.5% vs. 3.3%).

Each unit of packed RBC transfusion was linked to an increased risk of these complications, with adjusted odds ratios indicating a 1.45 times higher risk for prolonged ventilatory support and a 1.40 times higher risk for cardiac morbidity, highlighting the potential harms of RBC transfusions in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Outcomes of Perioperative Red Blood Cell Transfusions in Coronary Artery Bypass Grafting in Hospital Universiti Sains Malaysia. Chan, CH., Ziyadi, GM., Zuhdi, MA.[2023]

In a study involving 531 HIV-infected patients receiving 1745 transfusions, the use of WBC-reduced RBCs did not significantly lower the incidence of transfusion reactions, such as elevated temperature and hypotension, compared to unmodified RBCs.

Patients with a history of fever prior to transfusion were more likely to experience elevated temperatures during the transfusion, indicating that pre-existing conditions may influence transfusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signs and symptoms associated with the transfusion of WBC-reduced RBCs and non-WBC-reduced RBCs in patients with anemia and HIV infection: results from the Viral Activation Transfusion Study. Lane, TA., Gernsheimer, T., Mohandas, K., et al.[2019]

Red blood cell (RBC) transfusions are crucial for treating sickle cell anemia and thalassemia, but alloimmunization poses significant risks, potentially leading to severe complications.

Improving RBC matching beyond just ABO, Rh, and K antigens to include molecular antigenic matching could enhance transfusion safety and efficacy, particularly for patients with different genetic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing. Matteocci, A., Pierelli, L.[2022]

Switching from double-unit to single-unit red blood cell (RBC) transfusions in malignant hematology patients led to a 29% reduction in overall RBC utilization, indicating a more efficient use of resources.

The single-unit transfusion policy was found to be safe and effective, with no significant differences in length of hospital stay or 30-day mortality compared to the double-unit approach, although patients receiving single units had a lower mean hemoglobin at discharge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single versus double-unit transfusion: Safety and efficacy for patients with hematologic malignancies. Bowman, Z., Fei, N., Ahn, J., et al.[2020]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Worldwide audit of blood transfusion practice in critically ill patients. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

No Significant Association Between the Transfusion of Small Volumes of Leukocyte-Depleted Red Blood Cells and Mortality Over 7 Years of Follow-up in Patients Undergoing Cardiac Surgery: A Propensity Score Matched Analysis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Predicting red blood cell transfusion in hospitalized patients: role of hemoglobin level, comorbidities, and illness severity. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Storage time of transfused red blood cells and impact on clinical outcomes in hematopoietic stem cell transplantation. [2011]

6. United States pubmed.ncbi.nlm.nih.gov

In vitro lysis and acute transfusion reactions with hemolysis caused by inappropriate storage of canine red blood cell products. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Induction of platelet white blood cell (WBC) aggregate formation by platelets and WBCs in red blood cell units. [2008]

8. England pubmed.ncbi.nlm.nih.gov

Irradiation and prolonged storage of red cells are associated with increased adverse events. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Adverse effects of small-volume red blood cell transfusions in the neonatal population. [2021]

10. Malaysia pubmed.ncbi.nlm.nih.gov

Adverse Outcomes of Perioperative Red Blood Cell Transfusions in Coronary Artery Bypass Grafting in Hospital Universiti Sains Malaysia. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Signs and symptoms associated with the transfusion of WBC-reduced RBCs and non-WBC-reduced RBCs in patients with anemia and HIV infection: results from the Viral Activation Transfusion Study. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Single versus double-unit transfusion: Safety and efficacy for patients with hematologic malignancies. [2020]