Background: The World Health Organization defines anemia in females as a hemoglobin (Hb)<12g/dL and in men as a Hb<13g/dL1. These different Hb cutoffs for defining anemia represent well established differences in normal baseline Hb concentration between females and males. Moreover, there are also differences in the prevalence rates of anemia in females and males over the life course2. Despite these known differences in baseline Hb concentration and rates of anemia, there is little data describing whether females and males may also differ in their tolerance of anemia symptoms, such as fatigue, the primary symptom of anemia. This is important for hospitalized patients because if either males or females have higher anemia-related fatigue levels, then using the same Hb threshold to transfuse all hospitalized patients may not be the optimal management for either sex. Importantly, the RCT’s that have informed restrictive transfusion practices have not reported on sex differences in baseline Hb levels or how such differences may impact transfusion thresholds, particularly with respect to patients’ symptoms3. As such, the purpose of this study was to measure the fatigue levels of hospitalized patients with anemia, and to test for differences in the anemia-related fatigue levels of females and males.
Methods: From 7/2017-2/2020, hospitalized general medicine patients with a Hb<10g/dL were approached for an inpatient interview at hospital admission. As part of the inpatient interview patient’s fatigue was measured using the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 8a instrument. The PROMIS fatigue instrument is a well validated instrument for measuring anemia-related fatigue with scores ranging from 8-40, and higher scores indicating higher fatigue levels. Patients’ Hb values and clinical data were abstracted from the hospital’s administrative data mart. A multivariable linear regression model was used to test the association between fatigue as the dependent variable, patients’ sex as the primary predictor variable, controlling for age, race, ethnicity, nadir Hb level, Charlson Comorbidity Index, receipt of a transfusion, and length of stay.
Results: 1,931 patients completed the inpatient interview. Of these 58% were female and 42% were male. Females were slightly older than males in our sample (58 vs. 56, =0.01), There was a higher percentage of African American females than males (76% vs 66%), and a lower percentage of white females compared to white males (46% vs 54%) (p<0.01) in our sample. Females had a shorter LOS (9 vs. 10 days, p<0.01) and higher fatigue levels at admission (27 vs 24, p<0.01) compared to males. There were no other differences in baseline characteristics between males and females with respect to ethnicity, nadir Hb (mean 7.7g/dL (±1)), receipt of a transfusion (31%), or number of comorbidities. In the regression model, controlling for the above characteristics females had clinically significant higher fatigue levels than did males (β=3.0, p<0.01).
Conclusions: Hospitalized female patients have higher anemia-related fatigue levels than do hospitalized male patients. This difference in fatigue levels may represent different tolerances to anemia and a differential effect of low Hb levels during hospitalization on females compared to males. Future work should focus on identifying whether different Hb transfusion thresholds may be necessary to mitigate the effects of anemia on fatigue for females and males.