Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy

Abstract

Background: Chronic red blood cell transfusions reduce acute care utilization for sickle cell disease (SCD) pain. However, little is known about whether chronic transfusions treat or prevent the development of non-crisis pain. We investigated patient-report of pain in adults with SCD receiving chronic exchange transfusions (CET) compared to adults not on CET with similar disease characteristics.

Study method and design: Eleven participants receiving chronic exchange transfusion (CET) for at least one year were compared to 33 participants not receiving CET. Participants completed validated patient-reported outcomes regarding pain impact and quality of life at regularly scheduled visits or before CET. One year of health care utilization and opioid prescriptions were examined.

Results: After 1:1 propensity matching was performed for age, genotype, WBC and neutrophil counts, patients on CET had lower Pain Impact scores (-5.1, p = 0.03) and higher Neuropathic (7.4, p < 0.001) and Nociceptive Pain Quality (3.7, p < 0.001) scores, all indicating worse pain. However, CET was associated with a reduction in annual all cause admissions (-3.1, p < 0.001), length of stay (-2.1 days, p < 0.001) and ED visits (-2.7, p < 0.001). CET was not associated with differences in opioids dispensed.

Conclusions: After adjusting for disease characteristics, CET was associated with worse pain impact and neuropathic and nociceptive pain quality, lower health care utilization and with similar levels of opioids dispensed. This data suggest that CET may reduce hospitalizations for acute pain but may not adequately treat nociceptive or neuropathic pain in SCD.

Keywords: chronic pain; exchange transfusion; opioid use; pain crisis; sickle cell disease.

Figure 1.. Effect of chronic exchange transfusions (CET) on Pain and Health Care Utilization Outcomes Using Propensity Matching.

Estimated effects of CET on pain outcomes after 1:1 propensity matching for age, genotype, WBC, and total neutrophil count. The coefficient marked with the horizontal line shows the estimated effect of CET on patient-reported outcome pain domains in the figure on the left (an increase in scores represent worse symptoms and a decrease in scores represent better symptoms in all domains except in Pain Impact where lower scores represent worse symptoms and higher scores represent better symptoms) and on hospital utilization in the figure on the right (a decrease represents an estimated decrease in utilization). The vertical line shows 95% confidence intervals of the estimated effect. *p=<0.05, **p=<0.001

Figure 2.. Patient-reported Pain measures for those on chronic exchange transfusions (CET) compared to those not on CET.

Pain measures as assessed using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) and the Patient Reported Outcomes Measurement Information System (PROMIS), in patients with SCD on CET (black bars) compared to those not on CET (grey bars). The y-axis shows ASCQ-Me (Pain Impact, Pain Episode Frequency, Pain Episode Severity) and PROMIS (Neuropathic Pain, Nociceptive Pain) domain scores. A score of 50 is the median for the validation cohort and higher scores represent worse symptoms and lower scores represent better symptoms in all domains except in Pain Impact where lower scores represent worse symptoms and higher scores represent better symptoms. Ten is one standard deviation of the validation cohort for all domains. There were no significant differences in scores between the two groups for all measures assessed (p=>0.05).

Figure 3.. Quality of life domains for those on chronic exchange transfusions (CET) compared to those not on CET.

Quality of life domains as measured using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) and the Patient Reported Outcomes Measurement Information System (PROMIS), in patients with SCD on CET (black bars) compared to those not on CET (grey bars). The y-axis shows ASCQ-Me (Stiffness Impact, Social Functioning Impact, Emotional Impact, Sleep Impact) and PROMIS (Anxiety) domain scores. A score of 50 is the median for the validation cohort in all domains. Lower scores represent worse symptoms and higher scores represent better symptoms in all domains except for Anxiety where higher scores represent worse symptoms and lower scores represent better symptoms. Ten is one standard deviation from the mean of the validation cohort for all domains. *p=<0.05