The Effects of Transfusion on Fatigue, Activity, and Fatiguability among Hospitalized Patients with Anemia

PI: Micah Prochaska, MD, MS
Co-PI: David Meltzer, MD, PhD

Red blood cell (RBC) transfusion guidelines from multiple medical societies recommending restrictive transfusion practices, and the resulting shift in clinical practice toward restrictive transfusion, have occurred without clear evidence concerning the potential adverse effects on fatigue and functional outcomes. This is important because fatigue is the primary symptom of anemia. As such, anemia increases the tendency to become fatigued at any given level of activity (fatigability), increasing fatigue and decreasing activity, which may ultimately impair functional outcomes. Given this, the goals of transfusion may include reducing fatigability, minimizing fatigue and increasing activity, which should be expected to improve functional outcomes. Thus, data describing whether and how transfusion improves fatigability would be useful for clinicians when making transfusion decisions, helping them to identify hospitalized patients with anemia-related fatigue who would benefit from transfusion, while avoiding unnecessary transfusion in those that wouldn’t.

To begin to answer the important clinical question of whether transfusion provides a benefit for patient’s fatigability (reduced fatigue and/or increased activity), fatigue, and activity, this proposed pilot trial randomizes hospitalized patients with anemia to receive transfusion at: a) hemoglobin (Hb) <9g/dL (liberal transfusion), or b) Hb<7g/dL (restrictive transfusion), and is measuring self-reported fatigability, fatigue, and activity during hospitalization and 7 days after hospital discharge. This pilot trial is informed by observational data demonstrating transfusion reduces fatigability after hospital discharge and will: 1) determine the feasibility of and optimize recruitment/randomization and data collection protocols, and 2) collect scientifically necessary data on potential inclusion/exclusion criteria and fatigability levels in a representative sample of patients in order inform the final efficient design of a larger pragmatic trial. As a result, this pilot RCT will lay the scientific foundation necessary to successfully operate a full trial that will answer whether a liberal compared to a restrictive transfusion strategy improve patient’s fatigability, fatigue, and/or activity levels after hospital discharge?

Answers to these questions will improve clinical transfusion practice. Clinicians will be able to use the data from this trial to determine whether transfusion can and should be used to treat fatigue, and what effect doing so may also have patient’s functional capacity. Additionally, this data will help clinicians tailor transfusion to symptomatic patients who are likely to benefit with reduced fatigability, fatigue, and/or increased activity after hospital discharge. This will result in the improved use of transfusion and better patient outcomes compared uniform restrictive transfusion practices based on patient’s Hb concentration alone, and irrespective of clinical characteristics like fatigue level. Moreover, the data from this trial will help inform whether transfusion is useful in treating physiologic symptoms of anemia, and whether alternative transfusion strategies, such as symptom-driven transfusion, may improve patient outcomes compared to universal restrictive transfusion practices.