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

The clinical significance of the findings is also reflected in the results of the logistic regressions, which may be mapped to potential effects on functional status. Specifically, the odds of having a high fatigue level (FACIT <27) increase 90% for persons with a minimum Hb 7–8 g/dL compared with persons with a minimum Hb ≥8 g/dL. For persons with a minimum Hb <7 g/dL, point estimates suggest a smaller (50%) increase in the odds of high fatigue, but the 95% confidence interval overlaps heavily with the estimate of patients whose minimum Hb is 7-8 g/dL. While it might be expected that patients with a minimum Hb <7 g/dL have greater levels of fatigue compared with patients with a minimum Hb 7-8 g/dL, we did not observe such a pattern. One reason may be that the confidence intervals of our estimated effects are wide enough that we cannot exclude such a pattern. Another possible explanation is that in both groups, the fatigue levels are sufficiently severe, such that the difference in their fatigue levels may not be clinically meaningful. For example, a FACIT score of 23 to 26 has been shown to be associated with an ECOG performance status of 2 to 3, requiring bed rest for at least part of the day.³ Therefore, patients with a minimum Hb 7-8 g/dL (mean FACIT score = 24; Table 2) or a minimum Hb of <7 g/dL (mean FACIT score = 23; Table 2) are already functionally limited to the point of being partially bed bound, such that further decreases in their Hb may not produce additional fatigue in part because they reduce their activity sufficiently to prevent an increase in fatigue. In such cases, the potential benefits of increased Hb may be better assessed by measuring fatigue in response to a specific and provoked activity level, a concept known as fatigability.²⁰

That minimum Hb is more strongly associated with fatigue than any other measure of Hb during hospitalization may not be surprising. Mean, median, maximum, and discharge Hb may all be affected by transfusion during hospitalization that could affect fatigue. Admission Hb may not reflect true oxygen-carrying capacity because of hemoconcentration.

The association between Hb and fatigue in hospitalized patients is important because increased fatigue could contribute to slower clinical recovery in hospitalized patients. Additionally, increased fatigue during hospitalization and at hospital discharge could exacerbate the known deleterious consequences of fatigue on patients and their health outcomes^14,15 after hospital discharge. Although one previous study, the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS)⁸ trial, did not report differences in patients’ fatigue levels at 30 and 60 days postdischarge when transfused at restrictive (8 g/dL) compared with liberal (10 g/dL) Hb thresholds, confidence in the validity of this finding is reduced by the fact that more than half of the patients were lost to follow-up at the 30- and 60-day time points. Further, patients in the restrictive transfusion arm of FOCUS were transfused to maintain Hb levels at or above 8 g/dL. This transfusion threshold of 8 g/dL may have mitigated the high levels of fatigue that are seen in our study when patients’ Hb drops below 8 g/dL, and maintaining a Hb level of 7 g/dL is now the standard of care in stable hospitalized patients. Lastly, FOCUS was limited to postoperative hip fracture patients, and the generalizability of FOCUS to hospitalized medicine patients with anemia is limited.

Therefore, our results support guideline suggestions that practitioners incorporate the presence of patient symptoms such as fatigue into transfusion decisions, particularly if patients’ Hb is <8 g/dL.¹⁸ Though reasonable, the suggestion to incorporate symptoms such as fatigue into transfusion decisions has not been strongly supported by evidence so far, and it may often be neglected in practice. Definitive evidence to support such recommendations would benefit from study through an optimal trial¹⁸ that incorporates symptoms into decision making. Our findings add support for a study of transfusion strategies that incorporates patients’ fatigue level in addition to Hb concentration.

This study has several limitations. Although our sample size is large and includes patients with a range of comorbidities that we believe are representative of hospitalized general medicine patients, as a single-center, observational study, our results may not be generalizable to other centers. Additionally, although these data support a reliable association between hospitalized patients’ minimum Hb and fatigue level, the observational design of this study cannot prove that this relationship is causal. Also, patients’ Hb values were measured at the discretion of their clinician, and therefore, the measures of Hb were not uniformly measured for participating patients. In addition, fatigue was only measured at one time point during a patient’s hospitalization, and it is possible that patients’ fatigue levels change during hospitalization in relation to variables we did not consider. Finally, our study was not designed to assess the association of Hb with longer-term functional outcomes, which may be of greater concern than fatigue.