Association between hydroxycarbamide exposure and neurocognitive function in adolescents with sickle cell disease

Abstract

Summary Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease‐modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16–17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSβ+ thalassaemia; n = 52 HbSS/HbSβ0 thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSβ+ thalassaemia; n = 8 HbSS/HbSβ0 thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSβ0 thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSβ0 thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSβ+ thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSβ+ thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ0 thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD.

Cognitive performance as a predictor of healthcare transition in sickle cell disease

“…Recurrent micro‐infarctions and chronic hypoxic damage likely contribute to the development of cognitive deficits 42 . Our group and others have shown that treatment with hydroxycarbamide and elevated fetal haemoglobin were linked to improved cognitive functioning 23,43,44 . Although we did not establish a relationship between favourable transition outcomes and disease‐modifying therapy in our analysis, hydroxycarbamide may mitigate cognitive deficit in adolescents with SCD.…”

“…SCCRIP participants receive neurocognitive screening every four years starting at age four 20,23 . As these assessments were not clinical referrals, participants were not selected for prior neurologic findings, disease severity, or concern for cognitive decline.…”

Effects of hydroxyurea on brain function in children with sickle cell anemia

“…In another report, older age and low hemoglobin were associated with increased neurocognitive impairment 33 . HbF has been associated with significantly better verbal fluency in a study of adolescents 9 and better scores on particular cognitive measures in a study of adults 34 …”

Combination dose-escalated hydroxyurea and transfusion: an approach to conserve blood during the COVID-19 pandemic

“…Without chronic transfusion, these patients' risk of recurrent stroke is .50%. 1 Although treatment with hydroxyurea also provides some cerebrovascular benefits for patients with SCA, [2][3][4][5][6][7][8][9][10] chronic transfusion offers better stroke protection. Based on the results of the Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) clinical trial, patients with a history of stroke ideally should not transition to hydroxyurea-only treatment, because this may increase their risk of stroke.…”