Sickle cell vasoocclusion: many issues and some answers

Area of Science:

• Hematology
• Microcirculation Research
• Genetic Epidemiology

Background:

• Sickle cell disease pathophysiology involves hemoglobin S (HbS) polymerization under deoxygenation.
• Clinical severity of sickle cell disease exhibits significant individual variability.
• HbS polymerization is a key event but not the sole cause of vasoocclusion.

Purpose of the Study:

• To review the pathophysiology of sickle cell vasoocclusion.
• To present a two-step model of vasoocclusion.
• To discuss factors influencing sickle cell vasoocclusion.

Main Methods:

• Literature review of pathophysiology, genetic modifiers, and microcirculatory events.
• Presentation of a two-step vasoocclusion model: adhesion followed by obstruction.
• Discussion of rheologic and microcirculatory behaviors of sickle erythrocytes.

Main Results:

• Vasoocclusion is a microcirculatory event influenced by multiple factors.
• A proposed model involves initial adhesion of deformable cells, followed by obstruction from less deformable sickle cells.
• Factors like vascular interactions, red cell heterogeneity, and deoxygenation rates play crucial roles.

Conclusions:

• Sickle cell vasoocclusion is a complex process involving HbS polymerization and flow dynamics.
• Individual variations in sickle cell disease severity are linked to genetic modifiers.
• Understanding rheologic and microcirculatory factors is essential for managing sickle cell vasoocclusion.