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Assessing Teratogenic Changes in a Zebrafish Model of Fetal Alcohol Exposure

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Fetal Hemoglobin Decrease During Voxelotor Treatment.

Gonzalo De Luna¹, Anoosha Habibi¹, Stéphane Moutereau²

¹Sickle Cell Referral Center, Department of Internal Medicine, Henri-Mondor University Hospital- UPEC, Créteil, France.

European Journal of Haematology

|October 21, 2024

Summary

Voxelotor treatment for sickle cell disease patients led to a decrease in fetal hemoglobin (HbF) levels after six months. This finding raises concerns about potential rebound effects upon Voxelotor cessation due to its short half-life.

Keywords:

Voxelotor fetal hemoglobin hematopoiesis sickle cell disease

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Area of Science:

Hematology
Pharmacology
Genetics

Background:

Voxelotor improves sickle cell disease (SCD) by modifying hemoglobin-oxygen affinity, reducing anemia and hemolysis.
The effect of Voxelotor on fetal hemoglobin (HbF) levels in SCD patients remains largely unknown.
Understanding HbF dynamics is crucial for managing SCD and its complications.

Purpose of the Study:

To investigate the impact of Voxelotor treatment on fetal hemoglobin (HbF) levels in sickle cell patients.
To analyze changes in HbF percentage and mean corpuscular HbF over a 6-month treatment period.
To explore potential implications for SCD management and treatment cessation.

Main Methods:

Retrospective analysis of HbF levels in SCD patients treated with Voxelotor.
Measurement of HbF percentage using high-performance liquid chromatography (HPLC).
Assessment of mean corpuscular HbF (mchF) in treated patients.

Main Results:

A significant decrease in HbF levels was observed in sickle cell patients after 6 months of Voxelotor treatment.
This reduction in HbF may be linked to an increased lifespan of red blood cells, particularly those with lower HbF.
The study observed variations in HbF percentage and mchF in the cohort.

Conclusions:

Voxelotor treatment is associated with a reduction in fetal hemoglobin levels in sickle cell patients.
The observed decrease in HbF might be an indirect effect of increased red blood cell survival.
Further research is needed to address the risk of rebound HbF levels upon Voxelotor discontinuation, considering its short half-life.