Autonomic nervous system involvement in sickle cell disease

Area of Science:

• Hematology
• Neuroscience
• Physiology

Background:

• Sickle cell disease (SCD) involves abnormal hemoglobin-S (HbS) leading to vaso-occlusion, organ damage, and early mortality.
• Deoxygenated HbS polymerizes, causing red blood cell rigidity and microvascular blockage, a process poorly understood.
• Triggers for vaso-occlusive crisis (VOC) include cold, stress, and pain, suggesting a link to the autonomic nervous system (ANS).

Purpose of the Study:

• To investigate the potential role of the autonomic nervous system (ANS) in the pathophysiology of sickle cell disease (SCD).
• To review the known mechanisms of SCD vaso-occlusion and associated dysautonomia.
• To explore how ANS regulation of microvascular blood flow might contribute to sickle vaso-occlusive crises (VOC).

Main Methods:

• Review of existing literature on SCD pathophysiology, vaso-occlusion, and dysautonomia.
• Analysis of the connection between patient-reported VOC triggers (cold, stress, pain) and ANS function.
• Exploration of the ANS's role in regulating regional microvascular blood flow in the context of SCD.

Main Results:

• The precise trigger for the transition from steady-state SCD to vaso-occlusive crisis (VOC) remains unknown.
• Dysautonomia is associated with both sickle cell disease (SCD) and sickle trait.
• The ANS's influence on microvascular blood flow suggests a potential, yet under-investigated, role in sickle pathophysiology.

Conclusions:

• The autonomic nervous system (ANS) plays a significant, under-explored role in sickle cell disease (SCD) pathophysiology.
• Understanding ANS involvement in dysautonomia and microvascular regulation is crucial for elucidating sickle vaso-occlusive crisis (VOC) triggers.
• Further research into the ANS's contribution to SCD is warranted to better understand and manage VOC.