Sickle cell disease as a vascular disorder

Area of Science:

• Hematology
• Vascular Biology
• Genetics

Background:

• Sickle cell disease (SCD) involves abnormal hemoglobin S (HbS) red blood cells (RBCs) causing vaso-occlusion and vascular complications.
• SCD presents with distinct sub-phenotypes, including hyperhemolytic and high hemoglobin/viscosity, which contribute to diverse clinical manifestations.
• Hemolysis and vaso-occlusion are interconnected, exacerbating vascular issues in SCD.

Purpose of the Study:

• To review current literature on sickle cell disease (SCD) and vaso-occlusive crises (VOCs).
• To explore the potential of targeting P-selectin as a therapeutic strategy for SCD complications.
• To identify alternative and emerging treatments for VOCs and RBC sickling.

Main Methods:

• Systematic review of English-language PubMed articles from January 2000 to January 2019.
• Search terms included 'sickle cell disease,' 'vaso-occlusive crises,' and 'selectin.'
• Analysis of existing and experimental therapeutic strategies for SCD.

Main Results:

• P-selectin is identified as a key mediator linking hyperhemolysis and vaso-occlusion.
• Targeting P-selectin shows promise for managing vascular and vaso-occlusion-associated complications in SCD.
• Multiple therapeutic avenues are under investigation, including platelet inhibition, gene therapy, L-glutamine, and fetal hemoglobin induction.

Conclusions:

• Targeting P-selectin represents a potential therapeutic strategy for sickle cell disease (SCD).
• Diverse approaches, including gene therapy and L-glutamine, are being explored to combat vaso-occlusive crises (VOCs) and RBC sickling.
• Further research is needed to fully elucidate the efficacy of these strategies in managing SCD.