clinical topic updates

Vaso-Occlusive Crisis: Key Cellular Interactions

by Julie Kanter, MD

Overview

The understanding of the cellular processes involved in vaso-occlusive crises (VOCs) in sickle cell disease (SCD) has expanded greatly. Data from ongoing clinical trials and patient registries promise to further elucidate key interactions and therapeutic strategies.

Expert Commentary

Julie Kanter, MD

Associate Professor, Division of Hematology and Oncology
Director, Adult Sickle Cell Program
Codirector, Lifespan Comprehensive Sickle Cell Center
University of Alabama at Birmingham
Birmingham, AL

“I think that recent successes do validate the thinking regarding the role of P-selectin and neutrophils, and it is likely that the cellular interactions involved will continue to be elucidated through investigations that are ongoing and/or planned.

Julie Kanter, MD

We have known for some time that inflammation plays a role in SCD, and one of the things that we have come to understand is just how central the neutrophil is to the vaso-occlusive process. Individuals with SCD who have very extensive inflammation and high neutrophil counts have worse disease in terms of their frequency of VOCs. Consequently, understanding the role of the neutrophils and blocking their activity without causing an increase in infection remain important objectives. 

The success of crizanlizumab in SCD is exciting from the perspective of efficacy, as well as conceptually and scientifically. I think that it does validate the thinking regarding the role of P-selectin and neutrophils, and it is likely that the cellular interactions involved will continue to be elucidated through investigations that are ongoing and/or planned. We know that thrombotic mechanisms may be important, and it might be interesting to see whether blocking 2 pathways by adding something like a direct oral anticoagulant or platelet inhibitor can help even more. There are ongoing studies of crizanlizumab, some of which include patients who are also receiving hydroxyurea, an agent with a different mechanism of action. Long-term studies will likely further our understanding of the inflammatory pathways involved and of the value of combination therapy.

Clinicians who treat SCD—including myself—have formed a community called the National Alliance of Sickle Cell Centers with the goal of improving the quality of care for this population. This organization is working to harness a longitudinal clinical registry, the Globin Research Network for Data and Discovery (GRNDaD), to ensure that the clinical centers work collaboratively to compile information and evaluate outcomes at participating treatment centers. This registry (in combination with evaluations of quality improvement) should greatly improve the understanding of SCD at the population and cellular levels. For example, data compiled in the registry will enable us to compare outcomes in patients with neutrophilia vs in patients with lower neutrophil counts. Such data should prove invaluable for answering some of the outstanding questions regarding the inflammatory processes at work in VOCs.

References

Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429-439. doi:10.1056/NEJMoa1611770

Barbu EA, Dominical VM, Mendelsohn L, Thein SL. Neutrophils remain detrimentally active in hydroxyurea-treated patients with sickle cell disease. PLoS One. 2019;14(12):e0226583. doi:10.1371/journal.pone.0226583

Barbu EA, Mendelsohn L, Samsel L, Thein SL. Pro-inflammatory cytokines associate with NETosis during sickle cell vaso-occlusive crises. Cytokine. 2020;127:154933. doi:10.1016/j.cyto.2019.154933

Darbari DS, Sheehan VA, Ballas SK. The vaso‚Äźocclusive pain crisis in sickle cell disease: definition, pathophysiology, and management. Eur J Haematol. 2020;105(3):237-246. doi:10.1111/ejh.13430

National Alliance of Sickle Cell Centers. Accessed June 23, 2021. http://www.sicklecellcenters.org

More in Sickle Cell Disease

Thumb

Sickle Cell Disease

Safely Transfusing Patients With Sickle Cell Disease

Clinical Topic Updates by Stella T. Chou, MD

Red blood cell transfusions in sickle cell disease (SCD) may be used acutely to treat life-threatening complications or chronically as prophylaxis ...READ MORE

Thumb

Sickle Cell Disease

Vaso-Occlusive Crisis and Other Complications of Sickle Cell Disease

Clinical Topic Updates by Julie Kanter, MD

Vaso-occlusive crisis (VOC) and other complications such as ischemic stroke can create a substantial burden in patients with sickle cell disease (S...READ MORE

Thumb

Sickle Cell Disease

The Evolving Treatment Landscape for Sickle Cell Disease

Expert Roundtables by Stella T. Chou, MD; Michael Rutledge DeBaun, MD, MPH; and Julie Kanter, MD

Established treatments for sickle cell disease (SCD), such as hydroxyurea, have significantly improved outcomes. As novel therapies that target dis...READ MORE

More In Hematology

Sickle Cell Disease

Improving Access To Care In Patients With Sickle Cell Disease

Expert Roundtables by Stella T. Chou, MD; Michael Rutledge DeBaun, MD, MPH; and Julie Kanter, MD

Sickle Cell Disease

Reducing Pain Crises And Hospitalizations In Sickle Cell Disease

Expert Roundtables by Stella T. Chou, MD; Michael Rutledge DeBaun, MD, MPH; and Julie Kanter, MD

Sickle Cell Disease

Opioid Sparing Approaches In Sickle Cell Disease

Patient Care Perspectives by Michael Rutledge DeBaun, MD, MPH