Sickle Cell Disease Pain Crises Research Articles

Abortions Outcomes of People with Sickle Cell Disease

Introduction People with sickle cell disease (SCD) are at risk for SCD-associated complications with routine procedures. Whether people with SCD seeking abortions require special consideration is unknown. At our center, 28% of surveyed women with SCD reported having had an abortion, and 32% believed abortion to be unsafe for people with SCD. This cohort also reported low rates of long-acting contraception use. Information about abortion outcomes among people with SCD is important to inform care and minimize unnecessary delays, particularly as people in the U.S. face barriers to abortion access. The purpose of this study is to describe a single-center experience with abortions for people with SCD. Methods This single-center JHU IRB-approved study included people with SCD ages 18-55 years who had a medication or procedural abortion between April 1, 2013, and December 31, 2022. Systematic data collected from electronic health records included patient demographics, pregnancy information (e.g., gravidity), SCD characteristics (e.g., genotype), healthcare utilization, and abortion information, including the type of abortion, anesthesia and steroid use, pre- and post-abortion transfusion use, and the number and type of post-abortion complications. These complications included SCD complications (e.g., pain crises and acute chest syndrome) and non-SCD complications (e.g., infections and hemorrhage). SAS was used to generate descriptive statistics. Results There were 19 subjects with 27 abortions between 2013 and 2022. The median age at the time of abortion care was 24 years (IQR: 20-29). About half of the subjects with known genotypes (10/18, 56%) had HbSS/HbSβ0 thalassemia and accounted for an equal proportion of abortions (15/27, 56%). The nearest median hemoglobin level to abortion was 8.9 g/dL (IQR: 8.1-10.6). In 15/27 (56%) abortions, the subject was on disease-modifying therapy (hydroxyurea or chronic transfusions) before pregnancy, and two subjects stopped taking hydroxyurea during pregnancy. Six subjects who had 11/27 (41%) abortions in the cohort had ≥ five hospitalizations for pain crises in the year before abortion. Most abortions (24/27, 96%) were managed with a <30-minute dilation and curettage or dilation and evacuation. The median gestational age at the time of abortion care was 10 weeks (IQR: 8-14). Among procedural abortions (N=24), seven were treated with steroids. The rates of 7-day and 30-day complications for procedural abortions were 6/24 (26%) and 10/24 (42%), respectively, of which a majority were SCD pain crises (Table 1). Baseline pain crisis frequency was six times higher in subjects with post-abortion pain crises compared to those without. There was no difference in pain crisis after abortion between those with steroid use (4/7, 56%) compared to those without steroid use (8/16, 50%). Conclusions In this cohort, most abortions were procedural and required brief anesthesia. This does not routinely require prophylactic transfusion. Steroids, a risk factor for pain crises, were commonly used in procedural abortions. The high rate of baseline pain crises in this cohort confounded the association between abortions and post-abortion pain crises. People with HbSS/HbSβ0 thalassemia were underrepresented in our cohort when compared to the general SCD population. This may reflect differences in pregnancy rates or abortion decision-making within this group. Limitations include that this study is single-center and did not capture abortions performed outside our healthcare system. Larger studies are needed to define management and inform abortion care for people with SCD.

The Impact of Multi-System Trauma in Patients with Sickle Cell Disease

The impact of multi-system traumatic injury in patients with Sickle Cell Disease (SCD) is grossly understudied; only three published case studies have described such a relationship between sickle cell and multi-system trauma. These reports do not address prospective health outcomes following injury, despite strong biological plausibility to support adverse effects in trauma patients with sickle cell trait. It is likely, therefore, that trauma may increase acute complications such as vaso-occlusive events (VOC) and thus pain crises in SCD. We examined whether exposure to a traumatic injury is associated with an increase in frequency and duration of VOC. A retrospective chart review of 356 adult patients from 2000-2022 with SCD was performed, using data from electronic health record abstraction. A total of 96 patients were identified with a prior traumatic event (TE), defined as a sudden onset of physical injuries of any severity requiring an Emergency Department (ED) visit. Patients with missing data one-year pre- and post-TE, isolated injuries, or periods of incarceration were excluded. The 62 qualifying patients were then sorted into three primary comparison groups: (A) those with severe injuries (receiving triage by Trauma Team Activation (TTA) and admission), (B) moderate injuries (receiving triage by TTA but no admission), and (C) minor injuries (receiving neither triage by TTA nor admission). To further stratify by triage status alone, groups A and B were combined to compare against those with minor injuries (triage vs no-triage). TE hospital length of stay (LOS) and 30-day mortality were noted for all groups. To determine sickle cell-related outcomes, we recorded the time from TE discharge to first VOC event, as well as the number of VOC requiring an ED visit one-year pre- and post-TE. LOS for the VOC event immediately pre-TE was compared to the first VOC post-TE. We tested statistically significant changes in the frequency of ED visits, hospitalizations, and LOS for TE admission, stratifying pre-post estimates by severity of trauma. Favorable prospective health outcomes were defined as no significant difference in mortality, number of ED visits, hospitalizations, and VOC LOS pre- and post-TE. Our analysis determined that the earliest time to first VOC event post-TE was noted in patients with mild injuries at 826.3 hours, followed by patients with moderate injuries at 2349.2 hours, and patients with severe injuries at 3252.6 hours. This trend may imply that unresolved injuries from a lack of triage by TTA and disease management may contribute to early onset VOC. Two-sample t-tests report that the patient cohort with mild injuries observed a 28% increase in pain crises frequency post-injury (p=0.04), followed by patients with severe injury at 20% (p=0.24), and moderate injuries at 8% (p=0.16). These results may suggest that the cohorts of SCD patients with the most favorable prospective health outcomes were those who were ultimately admitted post-injury. Similarly, duration of first VOC post-injury increased for patients with severe injuries by 472% (p=0.78), followed by patients with moderate injuries by 202% (p=0.16), suggesting that high injury severity may contribute to longer VOC LOS. No statistical difference in 30-day mortality was noted between all cohorts. Our analysis was limited by small cohort sample sizes, retrospective documentation of SCD and trauma outcomes, and lack of precedence. Our findings are the first to provide preliminary evidence for an association between exposure to multi-system traumatic injury and poor SCD outcomes. This was especially true for patients classified as having mild traumatic injuries and thus not requiring triage by TTA or admission. In this subset, lack of further interventions following an injury may result in unforeseen physiologic stressors contributing to occurrence of VOC and prolonged hospital admissions. Only one patient of 356 record reviews had an Emergency Severity Index Triage (ESI) documented, despite NIH SCD Expert Panel's recommendation that all SCD patients be designated an ESI of 2. In SCD patients, further management of traumatic injuries, regardless of severity, may help to minimize future VOC events and other adverse outcomes. Further research is required to identify post-TE triage protocols, predict acute triggers for pain events, and target appropriate medical interventions for SCD patients suffering traumatic injuries. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

93 Patients With Sickle Cell Disease Pain Crises Are Often Undertreated in the Out-of-Hospital Setting: A Multi-Agency Cohort Study

93 Patients With Sickle Cell Disease Pain Crises Are Often Undertreated in the Out-of-Hospital Setting: A Multi-Agency Cohort Study

Global geographic differences in healthcare utilization for sickle cell disease pain crises in the CASiRe cohort

BackgroundSickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. ProcedureThe Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). ResultsThis study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.; 1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy's hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen. ConclusionsGeographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit.

Identifying elevated risk for future pain crises in sickle-cell disease using photoplethysmogram patterns measured during sleep: A machine learning approach.

Transient increases in peripheral vasoconstriction frequently occur in obstructive sleep apnea and periodic leg movement disorder, both of which are common in sickle cell disease (SCD). These events reduce microvascular blood flow and increase the likelihood of triggering painful vaso-occlusive crises (VOC) that are the hallmark of SCD. We recently reported a significant association between the magnitude of vasoconstriction, inferred from the finger photoplethysmogram (PPG) during sleep, and the frequency of future VOC in 212 children with SCD. In this study, we present an improved predictive model of VOC frequency by employing a two-level stacking machine learning (ML) model that incorporates detailed features extracted from the PPG signals in the same database. The first level contains seven different base ML algorithms predicting each subject's pain category based on the input PPG characteristics and other clinical information, while the second level is a meta model which uses the inputs to the first-level model along with the outputs of the base models to produce the final prediction. Model performance in predicting future VOC was significantly higher than in predicting VOC prior to each sleep study (F1-score of 0.43 vs. 0.35, p-value <0.0001), consistent with our hypothesis of a causal relationship between vasoconstriction and future pain incidence, rather than past pain leading to greater propensity for vasoconstriction. The model also performed much better than our previous conventional statistical model (F1 = 0.33), as well as all other algorithms that used only the base-models for predicting VOC without the second tier meta model. The modest F1 score of the present predictive model was due in part to the relatively small database with substantial imbalance (176:36) between low-pain and high-pain subjects, as well as other factors not captured by the sleep data alone. This report represents the first attempt ever to use non-invasive finger PPG measurements during sleep and a ML-based approach to predict increased propensity for VOC crises in SCD. The promising results suggest the future possibility of embedding an improved version of this model in a low-cost wearable system to assist clinicians in managing long-term therapy for SCD patients.

Global Geographic Differences in Healthcare Utilization for Sickle Cell Disease Pain Crises in the CASiRe Cohort

Background: Sickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. Procedure: The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). Results: This study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.;1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy’s hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen. Conclusions: Geographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit. Funding: This study was supported in part by research funding from Grant # NIMHD T37MD001425 to AC. Declaration of Interest: A Campbell: research funding and consultancy from Global Blood Therapeutics (GBT), Novartis; and consultancy for bluebird bio; D Manwani: research funding from Grifols; consultancy for Novartis, Pfizer, Global Blood Therapeutics; B Andemariam: consultancy for Bluebird bio, CRISPR/Vertex, Forma Therapeutics, Global Blood Therapeutics, Hemanext, Novartis, NovoNordisk, Cyclerion, Terumo, Roche, Sanofi-Genzyme; research funding from Global Blood Therapeutics, Imara, Novartis; B Inusa: education funding from Novartis AstraZeneca, Global Blood Therapeutics, Celgene, Vertex; C Strunk: consultancy for Global Blood Therapeutics, Forma Therapeutics, Novartis and Medunik USA; R Colombatti: research funding from Global Blood Therapeutics, BlueBird Bio; consultancy for Novartis, Addmedica, NovoNordisk; C Piccone: consultancy for Global Blood Therapeutics and Novartis; W Zempsky: consultancy for Glycomimetics and GlaxoSmithKleine. No disclosures to declare from the other co-authors. Ethical Approval: This study received IRB approval at each institution.

A Pilot Study of a Functional Pain Assessment for Adult Patients Admitted with Sickle Cell Pain Crisis

Introduction Acute vaso-occlusive pain crises are the most common complications of sickle cell disease (SCD). Pain is a subjective sensation and is often difficult to describe and for practitioners to understand. The complexity and multidimensional nature of pain requires additional evaluation beyond pain intensity. Pain assessment is also influenced by implicit and explicit biases related to race and ethnicity which can negatively influence treatment (Wandner et al J Pain 2012). In this pilot quality improvement study, we studied resident perceptions to a functional assessment tool in adult patients hospitalized with sickle cell vaso-occlusive crises. We used the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ), a validated questionnaire of physical function in youth experiencing acute pain (Zempsky et al J Pain 2014) (Figure 1). Resident responses to using the YAPFAQ were measured as an initial step to implementation of functional pain assessment in hospitalized adults with SCD pain crises. Methods We piloted this study on internal medicine residents. First, residents completed the Resident Acute SCD Pain Assessment Survey regarding their current management of acute pain in SCD (Figure 2). This was done to determine their baseline demographic information, methods of pain assessment, satisfaction with the numerical pain score system, and to understand barriers in assessing acute pain. This survey included a combination of multiple choice, free response, and binary response options. The residents then trialed the YAPFAQ with a patient admitted with vaso-occlusive pain crisis then the residents completed The Post YAPFAQ Evaluation Survey in response to this assessment tool (Figure 3). This survey included a combination of multiple choice, free response, and binary response options. The goal of this survey was to assess resident satisfaction with YAPFAQ, perceived patient receptiveness to YAPFAQ, and feasibility of using this tool during daily assessments. Patients were not surveyed during this pilot study. We performed descriptive statistics to describe the survey results. Results Sixteen residents completed the Acute SCD Pain Management survey prior to using the YAPFAQ. Sixty-nine percent of residents reported dissatisfaction with using numerical pain scores. Reported barriers to assessing pain included: subjectivity of pain scores, concern for malingering, and the ceiling effect of the numeric scale. Seven residents completed the post YAPFAQ evaluation survey. A majority of residents (86%) were extremely satisfied or satisfied with using the YAPFAQ. Fifty seven percent of residents felt that patients were extremely receptive or receptive to using this tool. The majority of residents (85%) felt that the YAPFAQ improved their understanding of patients' pain. All YAPFAQs were completed with patients in 10 minutes or less. Most residents (57%) reported that the tool would be feasible for implementation on rounds. Conclusions Similar to previous studies, our residents felt that numerical pain score systems inadequately describe pain. Residents had generally positive responses to the YAPFAQ. One resident stated that the questionnaire was "structured and easy to compare day to day." Functional pain assessment allows providers to better understand how pain limits daily activities and can provide useful functional targets for safe hospital discharge. Future directions of this project include performing a larger study of patients hospitalized with vaso-occlusive pain crises to validate the YAPFAQ in adult patients, survey patients regarding experiences with the YAPFAQ, and to create tailored pain management plans based on functional pain assessments. Disclosures No relevant conflicts of interest to declare.

Body Mass Index and the Association With Vaso-occlusive Crises in Pediatric Sickle Cell Disease.

Children with sickle cell disease (SCD) historically have been underweight and have poor overall growth. Recent studies have demonstrated a trend toward obesity in pediatric SCD populations. Through retrospective chart review of patients with SCD followed at our center, we collected patient's data, including body mass index (BMI), weight percentiles, sickle cell genotype, baseline hemoglobin, medical and psychiatric comorbidities, 25-hydroxy vitamin D level, treatment with hydroxyurea, and chronic transfusions. We identified hospitalizations to St. Christopher's Hospital for vaso-occlusive crisis (VOC) and duration of hospitalization and intravenous opioid use were recorded. Student t test, Mann-Whitney U test, and analysis of variance were used to examine associations between variables and frequency and duration of hospitalizations for VOC. Among 328 patients with SCD, overweight and obese children constituted 19% of hospitalized and nonhospitalized patients. BMI status did not influence frequency (P=0.90) or duration of hospitalization (P=0.65) for VOC. Obesity was more associated with HbSC than HbSS (P=0.025) genotype. Our study did not demonstrate an association between extremes of BMI of patients and hospitalization for VOC. Considering current trend toward obesity, further prospective and interventional research are required to define the effects of extremes of BMI on pain crises in SCD.

Initial outcomes of a comprehensive care model for sickle cell disease among a tribal population in rural western India

Background: Sickle cell disease (SCD) is the most prevalent inherited blood disorder worldwide, and is increasingly recognized as a neglected chronic disease. Several cost-effective interventions have dramatically reduced morbidity and mortality from SCD in developed countries. However, access to care for SCD in India is limited in most rural tribal regions with the highest SCD prevalence . Methods: In 2014, we implemented a comprehensive care model in rural Gujarat, India, with the aim of providing high-quality screening and treatment to increase coverage of proven interventions for sickle cell disease. Components of the intervention include: new-born, antenatal and family screening; outpatient sickle cell clinic; inpatient protocols; chronic disease registry; and health education. We followed a cohort of patients enrolled between February 2014 and October 2014 and compared the severity of disease and coverage of proven interventions at baseline and after one year of follow-up. Results: Of 164 patients diagnosed with sickle cell disease who enrolled in the comprehensive care program, 72 patients (43.9%) had SCD pain crises, 59 (35.9%) were hospitalized, 43 (26.2%) received blood transfusions, and 3 (1.8%) died during follow-up. Compared to baseline, coverage of pneumococcal vaccine (0.6% to 78.5%, p<0.001) and hydroxyurea (4.5% to 50.0%, p=0.002) significantly improved. There was a reduction in the proportion of patients with ≥3 pain crises per year (35.4% to 9.8%, p<0.001) and the proportion of patients with ≥1 hospitalization per year (56.7 go 36.0%, p<0.001) with no significant change in patients with ≥1 blood transfusion in last year (32.9% to 26.2%, p=0.127) . Conclusions: This study demonstrates that implementing a continuity care model for sickle cell disease in rural India is feasible and can improve coverage of evidence-based interventions.

Clinical and Geographic Characterization of 30-Day Readmissions in Pediatric Sickle Cell Crisis Patients.

Sickle cell disease (SCD) is a blood disorder affecting many US children that is often associated with hospital readmission. Although previous studies have reported on the clinical factors that influence readmission risk, potential geographic factors have not been fully investigated. The goal of this study was to investigate the importance of geographic risk factors and to confirm previously derived clinical risk factors that influence readmissions for SCD pain crises. Retrospective analyses were performed on pediatric inpatients with sickle cell crises at a single center. Readmission rates and risk factors were assessed. Geospatial analysis was conducted on point variables that represented health service access, and multivariable logistic regression models were constructed. The study identified 373 patients experiencing sickle cell crises, with 125 (33.5%) having at least one 30-day readmission. Age (mean difference: 2.2 years; P<0.001), length of stay (median difference: 1 day; P<.001), admission pain score>7 of 10 (odds ratio [OR]: 2.21; P<0.01), discharge pain score>4 of 10 (OR: 2.098; P<.01), living within 5 miles of the center's main hospital (OR: 0.573; P=.04), and >3 hospital utilizations in the previous 12 months (OR: 5.103; P<.001) were identified as potential indicators of 30-day readmission risk. Logistic regression models for 30-day readmissions yielded similar results. Increased age, high admission and discharge pain scores, decreased length of stay, and increased hospital utilizations were found to be associated with an increased risk of readmission for sickle cell crisis. Patient's residence was also found to be a significant risk indicator, supporting the utility of geospatial analysis in assessing readmission risk.

Prise en charge de la douleur drépanocytaire selon les critères de l'Organisation mondiale de la santé

Twenty-four percent of the Gabonese population has sickle cell trait, and 1–3% has sickle cell disease. Patients’ management must follow well-defined protocols that take into account the debilitating effect of severe pain episodes. Objectives. – To evaluate the three-step analgesic ladder for control of pain for sickle cell disease pain crises. Methodology. – This is a prospective and descriptive study based on surveys filled between February 2000 and March 2001. Surveys were restricted to sickle cell disease patients having developed pain crises before and during their stay at the hospital. The assessment of the pain was based on the DEGR and EVA scales. The treatment followed the World Health Organisation’s analgesic ladder. The criteria used for estimate pain severity and sedation duration were measured before, 2 and 24 h after treatment administration began (H0, H2 and H24) to evaluate its effectiveness. Results. – Sixty children were included. All the social layers of the population were represented. The school level was variable. Fifty-six percent of the patients suffered their first pain crisis before they were 1 year old. Thirty-one percent had annual crises and 20% monthly crises. Pain was located in joints in 35% of the cases, and in joints and bones in 15% of the cases. Eighty-one percent of the pain crises were successfully treated in stage I. The passage to stage II occurred in the remaining cases (18.3% of the cases). Conclusion. – The WHO’s three-step analgesic ladder for control of pain is effective for the sickle cell disease pain episodes. Stage I drugs relieved the pain for 81.6% of the patients in a relatively short time (2–16 h). It was not possible to go to stage III.