expert roundtables

Approach to Patients With a High Number of Vaso-Occlusive Crises in the Past Year

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

Overview

Patients with sickle cell disease (SCD) and frequent vaso-occlusive crises (VOCs) require a comprehensive multifaced approach. The best plans are guided by an understanding of the individual patient and the root causes of their VOC frequency.

Q:

What are the components of a good multifaceted approach to patients with SCD who have had frequent VOCs over the course of 1 year?

Michael Rutledge DeBaun, MD, MPH

Professor of Pediatrics and Medicine
Vice Chair for Clinical and Translational Research
J.C. Peterson Chair in Pediatrics
Director, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease
Vanderbilt University Medical Center
Nashville, TN

The frequency of ED visits or hospitalizations within 1 year is often used to assess the severity of SCD. However, most adults who have severe acute vaso-occlusive pain or men with priapism do not visit the ED or hospital; instead, they suffer at home.”

Michael Rutledge DeBaun, MD, MPH

The frequency of Emergency Department (ED) visits or hospitalizations within 1 year is often used to assess the severity of SCD. However, most adults who have severe acute vaso-occlusive pain or men with priapism do not visit the ED or hospital; instead, they suffer at home. Thus, the measurement of ED visits or hospitalizations is assuredly an underestimate of the disease severity.

The number of acute pain episodes justifying an escalation or change in disease-modifying therapy or curative therapy is ill-defined. If the patient is on hydroxyurea therapy, we escalate treatment after at least 1 to 2 acute vaso-occlusive pain episodes within a year. For children and adults receiving hydroxyurea therapy with multiple acute pain episodes (at home or in a hospital) requiring opioid treatment, our first step is to assess for adherence to hydroxyurea. If the patient acknowledges adherence to hydroxyurea therapy with corresponding laboratory changes (an increase in hemoglobin level, change in mean corpuscular volume, decreased absolute neutrophil count, and increased hemoglobin F level), we increase the dose of hydroxyurea, typically in 5-mg/kg increments.

A critical component before increasing the hydroxyurea dose or adding new therapies is a formal assessment for depression, anxiety, posttraumatic stress syndrome, and social determinants of health. If we identify mental health disease or modifying risk factors, such as homelessness, we strongly encourage counseling, social work intervention, or both. We then reevaluate over 8 to 12 weeks for a response. If there is no response, we repeat the approach until we reach a maximum-tolerated dose of hydroxyurea.

Often, an increase in the hydroxyurea dose will abate future acute vaso-occlusive pain episodes. In addition, we will evaluate for the presence of depression and potential psychosocial stressors that may contribute to acute vaso-occlusive pain episodes. If the patient is on hydroxyurea at the maximum-tolerated dose, we then consider crizanlizumab or L-glutamine. If the patient is not on hydroxyurea and is eligible for crizanlizumab or L-glutamine, we discuss those options with the patient. For all adults, we discuss the option of curative therapy if the acute pain episodes continue to degrade the patient’s quality of life.

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

“VOC has to be approached somewhat systematically, and the approach must be tailored to each individual, based, in part, on what has already been done.”

Julie Kanter, MD

A significant number of persons with SCD have pain crisis. As children age into adolescents and adults, they may have a more significant number of VOCs. VOC has to be approached somewhat systematically, and the approach must be tailored to each individual, based, in part, on what has already been done. Some individuals may not have had their disease-modifying SCD therapy maximized yet; others may not have had a solid pain plan in place yet. There is a need to meet patients where they are and to try to understand their particular circumstances. There, we are better positioned to determine what needs to be done, whether it is to start hydroxyurea, to increase the dose, or, perhaps, to take a look at other therapies. Some patients have already had their hydroxyurea maximized or they want a different option. There are many different options, and the path that we take very much depends on where the patient is, where they want to be, and what options they want to pursue.

We do have a few patients in our care who, despite every part of maximal therapy that we have tried, continue to have significant VOCs. Many of these patients have comorbid depression or anxiety, and we will often work with our partners in psychology to try to get to the root cause of what is happening, and then we will develop a combined pain plan with adjunct options, including a psychology management plan.

Stella T. Chou, MD

Associate Professor of Pediatrics
Chief, Division of Transfusion Medicine
Children’s Hospital of Philadelphia
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

“Patients with SCD are at risk for psychological comorbidities, some of which may present themselves in the context of pain, and this may be a driver for the observation that ED visits and admissions can occur in clusters.” 

Stella T. Chou, MD

A metric that we follow is the frequency with which they present to the ED and subsequently are admitted to the hospital. If this occurs more than once per month, it would be considered frequent. But, as Dr Kanter alluded to, patients with SCD are at risk for psychological comorbidities, some of which may present themselves in the context of pain, and this may be a driver for the observation that ED visits and admissions can occur in clusters. This also underscores the importance of having an individualized care plan that helps to guide and establish with the patient the criteria for visiting the ED, the criteria for them to be admitted, and the criteria for receiving outpatient medications.

Sometimes, seeing patients more frequently on an outpatient basis can be very helpful. When we feel that we have maximized therapy, we will see them once per week or every other week in the clinic, where they may also meet with our psychologist, who is a part of our SCD care team. We do screen for depression and anxiety, and some patients may benefit from antidepressants or antianxiolytics and/or referral for psychiatric care.

Regarding the role of chronic transfusion therapy, the risk-to-benefit ratio should always be considered, and current American Society of Hematology guidelines recommend against such therapy in the routine approach to frequent acute VOC. There may be exceptions in particular scenarios, however.

References

Chou ST, Alsawas M, Fasano RM, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327-355. doi:10.1182/bloodadvances.2019001143

Idris IM, Abba A, Galadanci JA, et al. Men with sickle cell disease experience greater sexual dysfunction when compared with men without sickle cell disease. Blood Adv. 2020;4(14):3277-3283. doi:10.1182/bloodadvances.2020002062

Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750-760. doi:10.1172/JCI89741

Osunkwo I, Manwani D, Kanter J. Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease. Ther Adv Hematol. 2020;11:2040620720955000. doi:10.1177/2040620720955000

Smith WR, Penberthy LT, Bovbjerg VE, et al. Daily assessment of pain in adults with sickle cell disease. Ann Intern Med. 2008;148(2):94-101. doi:10.7326/0003-4819-148-2-200801150-00004

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