Association Between Anemia and Fatigue in Hospitalized Patients: Does the Measure of Anemia Matter?

Fatigue is the most common clinical symptom of anemia and is a significant concern to patients.^1,2 In ambulatory patients, lower hemoglobin (Hb) concentration is associated with increased fatigue.^2,3 Accordingly, therapies that treat anemia by increasing Hb concentration, such as erythropoiesis stimulating agents,^4-7 often use fatigue as an outcome measure.

In hospitalized patients, transfusion of red blood cell increases Hb concentration and is the primary treatment for anemia. However, the extent to which transfusion and changes in Hb concentration affect hospitalized patients’ fatigue levels is not well established. Guidelines support transfusing patients with symptoms of anemia, such as fatigue, on the assumption that the increased oxygen delivery will improve the symptoms of anemia. While transfusion studies in hospitalized patients have consistently reported that transfusion at lower or “restrictive” Hb concentrations is safe compared with transfusion at higher Hb concentrations,^8-10 these studies have mainly used cardiac events and mortality as outcomes rather than patient symptoms, such as fatigue. Nevertheless, they have resulted in hospitals increasingly adopting restrictive transfusion policies that discourage transfusion at higher Hb levels.^11,12 Consequently, the rate of transfusion in hospitalized patients has decreased,¹³ raising questions of whether some patients with lower Hb concentrations may experience increased fatigue as a result of restrictive transfusion policies. Fatigue among hospitalized patients is important not only because it is an adverse symptom but because it may result in decreased activity levels, deconditioning, and losses in functional status.^14,15While the effect of alternative transfusion policies on fatigue in hospitalized patients could be answered by a randomized clinical trial using fatigue and functional status as outcomes, an important first step is to assess whether the Hb concentration of hospitalized patients is associated with their fatigue level during hospitalization. Because hospitalized patients often have acute illnesses that can cause fatigue in and of themselves, it is possible that anemia is not associated with fatigue in hospitalized patients despite anemia’s association with fatigue in ambulatory patients. Additionally, Hb concentration varies during hospitalization,¹⁶ raising the question of what measures of Hb during hospitalization might be most associated with anemia-related fatigue.

The objective of this study is to explore multiple Hb measures in hospitalized medical patients with anemia and test whether any of these Hb measures are associated with patients’ fatigue level.

Study Design

We performed a prospective, observational study of hospitalized patients with anemia on the general medicine services at The University of Chicago Medical Center (UCMC). The institutional review board approved the study procedures, and all study subjects provided informed consent.

Study Eligibility

Between April 2014 and June 2015, all general medicine inpatients were approached for written consent for The University of Chicago Hospitalist Project,¹⁷ a research infrastructure at UCMC. Among patients consenting to participate in the Hospitalist Project, patients were eligible if they had Hb <9 g/dL at any point during their hospitalization and were age ≥50 years. Hb concentration of <9 g/dL was chosen to include the range of Hb values covered by most restrictive transfusion policies.^8-10,18 Age ≥50 years was an inclusion criteria because anemia is more strongly associated with poor outcomes, including functional impairment, among older patients compared with younger patients.^14,19-21 If patients were not eligible for inclusion at the time of consent for the Hospitalist Project, their Hb values were reviewed twice daily until hospital discharge to assess if their Hb was <9 g/dL. Proxies were sought to answer questions for patients who failed the Short Portable Mental Status Questionnaire.²²

Patient Demographic Data Collection

Research assistants abstracted patient age and sex from the electronic health record (EHR), and asked patients to self-identify their race. The individual comorbidities included as part of the Charlson Comorbidity Index were identified using International Classification of Diseases, 9th Revision codes from hospital administrative data for each encounter and specifically included the following: myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia and/or paraplegia, renal disease, cancer, and human immunodeficiency virus/acquired immunodeficiency syndrome.²³ We also used Healthcare Cost and Utilization Project (www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp) diagnosis categories to identify whether patients had sickle cell (SC) anemia, gastrointestinal bleeding (GIB), or a depressive disorder (DD) because these conditions are associated with anemia (SC and GIB) and fatigue (DD).²⁴