Vaso-Occlusion in Sickle Cell Disease: Is Autonomic Dysregulation of the Microvasculature the Trigger?

Journal of Clinical Medicine. 2019;8(10):1690 DOI 10.3390/jcm8101690

 

Journal Homepage

Journal Title: Journal of Clinical Medicine

ISSN: 2077-0383 (Online)

Publisher: MDPI AG

LCC Subject Category: Medicine

Country of publisher: Switzerland

Language of fulltext: English

Full-text formats available: PDF, HTML, ePUB, XML

 

AUTHORS


Saranya Veluswamy (Hematology Section, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, 4650 Sunset boulevard, Los Angeles, CA 90027, USA)

Payal Shah (Hematology Section, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, 4650 Sunset boulevard, Los Angeles, CA 90027, USA)

Christopher C. Denton (Hematology Section, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, 4650 Sunset boulevard, Los Angeles, CA 90027, USA)

Patjanaporn Chalacheva (Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, Los Angeles, CA 90089, USA)

Michael C. K. Khoo (Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, Los Angeles, CA 90089, USA)

Thomas D. Coates (Hematology Section, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, 4650 Sunset boulevard, Los Angeles, CA 90027, USA)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 11 weeks

 

Abstract | Full Text

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by polymerization of hemoglobin S upon deoxygenation that results in the formation of rigid sickled-shaped red blood cells that can occlude the microvasculature, which leads to sudden onsets of pain. The severity of vaso-occlusive crises (VOC) is quite variable among patients, which is not fully explained by their genetic and biological profiles. The mechanism that initiates the transition from steady state to VOC remains unknown, as is the role of clinically reported triggers such as stress, cold and pain. The rate of hemoglobin S polymerization after deoxygenation is an important determinant of vaso-occlusion. Similarly, the microvascular blood flow rate plays a critical role as fast-moving red blood cells are better able to escape the microvasculature before polymerization of deoxy-hemoglobin S causes the red cells to become rigid and lodge in small vessels. The role of the autonomic nervous system (ANS) activity in VOC initiation and propagation has been underestimated considering that the ANS is the major regulator of microvascular blood flow and that most triggers of VOC can alter the autonomic balance. Here, we will briefly review the evidence supporting the presence of ANS dysfunction in SCD, its implications in the onset of VOC, and how differences in autonomic vasoreactivity might potentially contribute to variability in VOC severity.