The iTADS trial will test an important blood donor characteristic - donor sex - to see whether male donor blood leads to a greater benefit for transfusion recipients compared to female donor blood.

The trial will help determine how the investigators can tailor the selection of blood donors based on donor characteristics (e.g. sex) to further improve the safety and optimize the clinical benefit of blood products in Canada.

The investigators have designed an innovative pragmatic randomized trial that will allocate transfusion recipients to receive either only male or only female donor transfusions.

Primary objective:

To confirm that a transfusion strategy of receiving male donor RBC (Red Blood Cell) units only will improve survival compared to a transfusion strategy of female donor RBC units in all hospital patients requiring a transfusion.

Secondary objectives:

1. To assess effects of male RBC units on major morbidities (cancer, infection, end-organ damage)
2. To assess effects across major patient subgroups (major surgery, intensive care, oncology)
3. To assess the effect of female donor pregnancy history on recipient transfusion outcome
4. To build capacity to conduct large innovative prospective pragmatic clinical trials in transfusion medicine using routinely collected clinical and administrative information.

Inclusion Criteria:

• All patients (excluding neonates) requiring one or more allogeneic RBC transfusions for the treatment of anemia will be included.

Exclusion Criteria:

• Patients that do not have a valid Ontario Health Insurance Plan (OHIP) number at time of first transfusion
• Patients that require emergent release of a RBC transfusion and in whom emergency randomization could not be completed
• Patients with complex antibody profile in which it is impossible to match RBC units