LAUSR

Females have lower normal baseline hemoglobin (Hb) concentrations than males, and consequently, the Hb cutoffs that define anemia differ between sexes [1]. Females and males also differ in their red blood cell (RBC) mass, which results in differential incremental changes in Hb concentration after RBC transfusion depending on the sex of both the donor and recipient [2]. Based on these differences, it might also be expected that females and males differ in the severity of their anemia symptoms, since anemia symptoms are in part the physiologic response to the decreased tissue oxygenation of lower Hb [3]. Indeed, data from studies in ambulatory patients with MDS have suggested an association between sex and anemia-related fatigue [4, 5]. However, knowing whether this association is also true broadly in hospitalized general medicine patients is important because if females and males have different severity of symptoms at any given Hb level, then using the same restrictive Hb threshold to transfuse all patients may not be the optimal management for either sex. The RCTs that have informed restrictive transfusion practices have however not reported on sex differences in baseline Hb levels or how such differences may impact transfusion thresholds, particularly with respect to patients’ symptoms. Therefore, the purpose of this study was to test whether the severity of fatigue and other symptoms of anemia differ between hospitalized females and males in relation to Hb levels. Data for this analysis comes from an ongoing prospective observational study of hospitalized general medicine patients with a Hb < 10 g/dL, who have self-reported fatigue and other symptoms of anemia measured during their hospitalization. Self-reported fatigue and other symptoms of anemia were measured during hospitalization using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) anemia subscale (AnS) [6]. Higher FACIT-F scores reflect less fatigue or symptoms from anemia, and a difference of ≥ 3 on the FACIT-F represents a clinically significant difference. To determine whether the levels of fatigue and anemia symptoms differed significantly by sex, unadjusted mean FACIT-F scores were compared between females and males using t-tests across strata of nadir Hb concentrations. Multivariable linear regression models were also run to test the association between fatigue and symptoms (FACIT-F) as the dependent variable, and sex, nadir Hb, and a sex-nadir Hb interaction term as independent predictor variables. Comprehensive study methods, including model specification, are described in Appendix 1. The baseline characteristics of the study sample (n = 1120) are reported in Supplemental Table 1 (Appendix). Females had clinically worse fatigue and anemia symptom levels than did males overall and within each Hb strata, and these differences were statistically significant for each stratum except Hb 7.9–7.0 g/dL (Supplemental Table 2, Appendix). In a non-stratified fully adjusted regression model, females had levels of fatigue and symptoms that were greater than males and nearly an entire standard deviation above baseline levels (β = − 16, p = 0.01). The effect of the interaction term of sex-nadir Hb in the model also suggests additional and greater changes in fatigue and symptoms of anemia occur for females compared to males, at different levels of nadir Hb (β = 1.4, p = 0.06). In a regression model stratified by sex, lower nadir Hb was significantly associated with higher fatigue and anemia symptoms for females (β = − 1.6, p = 0.03), but not for males (β = 0.66, p = 0.44) (Table 1). As a result, the data from this study suggests that females have both clinically and statistically significant higher levels of fatigue and worse symptoms of anemia than do males at any given Hb < 10 g/dL, and also that females * Micah T. Prochaska [email protected]