Literature Review of Fatigue Scales and Association with Clinically Meaningful Improvements in Outcomes Among Patients With and Without Paroxysmal Nocturnal Hemoglobinuria

Adv Ther. 2022 May;39(5):1959-1975. doi: 10.1007/s12325-022-02111-7. Epub 2022 Mar 22.


Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder characterized by anemia and debilitating fatigue. Limited evidence characterizes the association between hemoglobin, an indicator of anemia and disease activity, and patient-reported fatigue scales. This review identifies benchmarks for clinically meaningful improvements in patients with and without PNH.

Methods: MEDLINE, Embase, Cochrane, and PsycINFO databases were searched along with Google Scholar to identify publications for patients with and without PNH. Full-text articles and conference abstracts of clinical trials or observational studies that examined patient-reported fatigue or associations between fatigue and hemoglobin were included.

Results: Fourteen publications were included in this study. Four clinical trials conducted in patients with PNH reported that patients achieved and sustained clinically meaningful improvements in fatigue. However, these studies did not examine the association between fatigue and hemoglobin. Ten studies conducted in patients with cancer and anemia (with or without chemotherapy) demonstrated an association between increased hemoglobin and improvements in fatigue (P < 0.05). The greatest incremental gain in fatigue improvement was observed when hemoglobin increased from 11 to 12 g/dL.

Conclusion: Evidence among patients with cancer without PNH demonstrates that increased hemoglobin levels are associated with clinically significant improvements in fatigue. Future studies should validate this relationship among patients with PNH.

Keywords: Fatigue; Hemoglobin; PNH; Paroxysmal nocturnal hemoglobinuria; Quality of life.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fatigue / etiology
  • Hemoglobinuria, Paroxysmal* / complications
  • Hemoglobinuria, Paroxysmal* / drug therapy
  • Humans