Significant Fatigue Common in Adult Patients with Sickle Cell Disease

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Data from a descriptive, prospective study in France revealed that most stable patients with sickle cell disease (SCD), the most prevalent monogenic disorder worldwide, experience significant, and often intense, symptoms of fatigue.¹

The study was the first to use the Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-Fatigue) questionnaire to specifically evaluate fatigue in a population of consecutive adult patients with SCD.² The scale ranges from 0 (worst fatigue) to 52 (no fatigue), with a threshold of <34 considered for diagnosis of significant fatigue.

According to the analysis, the median FACIT-Fatigue score among more than 100 patients with SCD was 29, with approximately two-thirds of the population below the described significant threshold of 34.¹

“Our present results indicated that most stable adult patients with SCD experience significant and sometimes intense fatigue,” wrote the investigative team, led by Geoffrey Cheminet, Université Paris Cité.¹ “The factors associated with the level of fatigue included female sex, a high level of stress, poor sleep quality, and the lifetime number of acute chest syndrome (ACS) episodes, but not the hemoglobin level or the SCD genotype.”

The course of SCD is defined by chronic hemolytic anemia, a recurrence of painful vaso-occlusive crises (VOCs), and acute and chronic damage with multi-organ involvement.³ It can significantly impact patient-reported health outcomes and quality of life, with a recent survey identifying ‘fatigue’ as the main patient-reported symptom.

A link between fatigue and VOCs and the severity of the disease has not been previously analyzed. The FACIT-Fatigue scale has been applied for a range of chronic conditions, including stroke, AIDS, skin disorders, and hematological cancers. These data revealed a cutoff of 43 indicating fatigue impairment in a healthy general population.⁴

In the current analysis, stable adults with SCD were asked to complete the 13-item FACIT-Fatigue questionnaire over 2 months, reflecting on their feelings of fatigue about the prior 7 days.¹ Using the national referral center’s database, investigators collected information on body mass index (BMI), the presence of SCD-modifying treatment, and the number of hospital admissions for VOCs in the previous year.

Among 103 identified adults with SCD, 102 were included during the 2-month study period, with a median age of 26 years. Patients had experienced an average of 1 hospital admission for VOCs in the previous year and 80 (78.4%) had a history of ACS. Hydroxyurea treatment was prescribed to 71 (69.6%) patients and 21 (20.6%) were in a long-term transfusion program.

After performing multivariate analysis, a lower FACIT-Fatigue score was independently, significantly associated with female sex, a high BMI, greater stress levels, poor sleep quality, and the number of previous ACS episodes. However, no association between the score and fatigue was identified with the hemoglobin level or the SCD genotype.

Based on these findings, Cheminet and colleagues indicated the need to measure fatigue systematically during SCD consultations and emphasized the importance of patient education about this assessment.

“In view of our present results, we believe that it would be legitimate to address fatigue more systematically in consultations, discuss this issue during patient education programs, and add fatigue as an end-point in therapeutic trials in SCD,” they wrote.

References

1. _{Cheminet G, Corbasson A, Charmettan M, et al. Assessment of fatigue in adult patients with sickle cell disease: Use of the functional assessment of chronic illness therapy-Fatigue (FACIT-fatigue) questionnaire. Br J Haematol. Published online May 27, 2024. doi:10.1111/bjh.19568}
2. _{Piel FB, Rees DC, DeBaun MR, et al. Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission. Lancet Haematol. 2023;10(8):e633-e686. doi:10.1016/S2352-3026(23)00096-0}
3. _{Montan I, Löwe B, Cella D, Mehnert A, Hinz A. General Population Norms for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale. Value Health. 2018;21(11):1313-1321. doi:10.1016/j.jval.2018.03.013}
4. _{Eek D, Ivanescu C, Corredoira L, Meyers O, Cella D. Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia. J Patient Rep Outcomes. 2021;5(1):27. Published 2021 Mar 11. doi:10.1186/s41687-021-00294-1}