Vaso-occlusive Episodes Research Articles

Identifying Gaps in Sickle Cell Disease Healthcare Resources across Hematology Clinics in California

Abstract Sickle cell disease (SCD) represents a major health challenge, affecting more than 100,000 people in the United States. Patients develop severe systemic manifestations from vaso-occlusive episodes, leading to severe pain crises and reduction of life expectancy. Despite its prevalence, individuals with SCD face not only dire health complications but also encounter systemic barriers in healthcare access and treatment. This exploratory study aims to provide preliminary insights into these challenges by examining the healthcare landscape for SCD patients in California, focusing on the accessibility and distribution of hematology clinics’ resources. Through a collaborative multi-site survey conducted, the study gathered insights from 44 hematology clinics. We explored adherence to treatment guidelines, the availability of specialty referrals, support services, clinic operational hours, and the impact of patient population size on service provision. The findings reveal potential gaps in guideline adherence, specialty referrals, and clinic operation times in clinics that serve ≤40 SCD patients. There is a scarcity of support roles such as community health workers and healthcare navigators across all clinics regardless of SCD population size. These preliminary insights underscore the need for further research and strategic interventions to improve access to comprehensive care and support for SCD patients. By highlighting potential disparities faced by SCD patients in California, this study provides a foundation for public health institutes to assess healthcare resources and develop effective solutions to enhance patient outcomes and quality of life.

Safety and Tolerability of Intravenous Lidocaine Infusions as Opioid Adjunct for Children Hospitalized With Sickle Cell Vaso-Occlusive Pain.

Sickle cell disease (SCD) vaso-occlusive episode (VOE) pain is treated with opioids, and non-opioid adjuvants may reduce pain severity without opioid side effects. We retrospectively investigated the safety and tolerability of intravenous lidocaine infusions as an adjunct to opioids in children and adolescents during VOE hospitalizations. In 2 years, lidocaine was administered in 64.6% of 260 admissions. There were no serious toxicities; overall, 82.2% of recipients chose to receive lidocaine during subsequent admissions. Lidocaine infusions were associated with longer hospitalizations, potentially reflecting selection bias. The efficacy of adjuvant lidocaine infusions during VOE should be studied prospectively.

Impact of Individualized Versus Weight-Based Pain Protocols on Patient Satisfaction for Patients With Sickle Cell Disease Experiencing a Vaso-Occlusive Episode.

Impact of Individualized Versus Weight-Based Pain Protocols on Patient Satisfaction for Patients With Sickle Cell Disease Experiencing a Vaso-Occlusive Episode.

Maternal and Infant Outcomes in a Subset of Patients with Sickle Cell Disease in South Carolina.

Sickle cell disease (SCD), which disproportionately affects minorities, increases complications during pregnancy. Severe maternal mortality is increased in women with SCD, including morbidity related to the disease and other nondisease-related complications. It also can have devastating complications for fetuses, with increases in premature birth and low birth weight. This study aimed to describe the characteristics of women with SCD in South Carolina, with a specific focus on fetal and maternal outcomes and complications. The secondary aim of this study was to identify the effect of maternal characteristics on birth outcomes, including social determinants of health. A secondary analysis of women from a single institution, the Medical University of South Carolina, which was part of the registry from the multi-institutional Sickle Cell Disease Implementation Consortium, was conducted. Patient demographics, self-reported pregnancy history, hydroxyurea use, and maternal and fetal outcomes were collected from patient-reported survey data. In addition, the number of vaso-occlusive episodes surrounding their pregnancies was collected for analysis. Fifty-nine percent (116/195) of the female participants reported ever being pregnant. Seventy-two percent had live births, 15.8% had miscarriages, 1.8% had stillbirths, and 6.1% had an abortion. The mean age was 22.3 ± 4 years, with no difference in markers of severity between the groups. Most women were HbSS genotype with high rates of pain in the last year. No difference was found in age, education, employment, or income between these groups of women. Women in the nonlive birth cohort had higher body weights (78.7 versus 72.1 kg, P = 0.045). The Distressed Community Index was used as a marker for social determinants of health and was similar between the two groups, with a majority of both cohorts (61.7% and 52%) living in "at risk" and "distressed" communities. Complications related to SCD were high, including 43% of women experiencing pain during pregnancy, 5.2% developing acute chest syndrome, and 22.4% requiring transfusion. An additional 11% experienced preeclampsia. Unfavorable infant outcomes included 49% of the infants being premature and 40% having babies weighing less than 5.5 lb at birth. High rates of complications to both mother and infant were found in the women with SCD. Although few statistically significant predictors were found, by identifying and addressing specific needs of pregnant women with SCD, we can work toward reducing fetal and maternal mortality in an already vulnerable population.

WHOQOL-BREF in Measuring Quality of Life Among Sickle Cell Disease Patients with Leg Ulcers.

Sickle cell disease (SCD) presents complex clinical manifestations influenced by genetic, social, environmental, and healthcare access factors as well as socioeconomic status. In this context, sickle cell leg ulcers (SLUs) are a debilitating complication of SCD. We aimed to describe sociodemographic data and evaluate the quality of life (QoL) of SCD patients with and without SLUs. We conducted a cross-sectional study including 13 SCD patients with SLUs and 42 without LUs. Clinical data were obtained by reviewing the medical records, and QoL was assessed with the WHOQOL-BREF questionnaire. Our cohort of patients had a mean age of 34.9 years, with 52.8% male, 52.8% identifying as black, and 41.7% identifying as brown. Most had low income, incomplete education, and high unemployment rates. The social habits and relationships of SCD patients showed varying levels of friendship and family closeness, and the majority of SLU+ patients did not practice sports. We failed to find statistical differences in the WHOQOL-BREF domains between SLU+ and SLU- patients. However, higher income and employment status were associated with improved WHOQOL-BREF domain scores in SCD patients, while vaso-occlusive episodes and female gender were linked to lower scores. Our data reinforce the sociodemographic characteristics of SCD. The physical domain was associated with income, occupation, and vaso-occlusion. The psychological domain was associated with income and occupation. The social relationship domain was associated with occupation and female gender. The environmental domain was associated with vaso-occlusion. The WHOQOL-BREF is a reliable tool to measure QoL in SCD.

CRISPR/Cas9 System as a Promising Therapy in Thalassemia and Sickle Cell Disease: A Systematic Review of Clinical Trials.

Clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system is a new gene editing tool that represents a revolution in gene therapy. This study aimed to review the clinical trials conducted to evaluate the efficacy and safety of the CRISPR/Cas9 system in treating thalassemia and sickle cell disease (SCD). We searched relevant literature using "CRISPR Cas", "thalassemia", "sickle cell" and "clinical trial" as subject terms in PubMed, Cochrane, Web of Science, and Google Scholar up to December 3rd, 2023. Following the PIO format (Patients, Intervention, Outcome), PRISMA guidelines were followed in the study selection, data extraction, and quality assessment processes. Out of 110 publications, 6 studies met our eligibility criteria with a total of 115 patients involved. CRISPR/Cas9 system was used to disrupt BCL11A gene enhancer in 4 studies and to disrupt γ-globin gene promoters in 2 studies. Patients demonstrated significant activation of fetal hemoglobin, elevated total hemoglobin, transfusion independence in thalassemia, and repression of vaso-occlusive episodes in SCD. Using CRISPR/Cas9 system to directly disrupt genes provides a safe and potential one-time functional cure for thalassemia and SCD, suggesting CRISPR/Cas9 as a potential therapeutic tool for the treatment of inherited hematological disorders.

Influence of Weather on Sickle Cell Disease Vaso-Occlusive Episodes and Acute Chest Syndrome: A Nationwide Sample Analysis.

The clinical manifestations of sickle cell disease (SCD) result in significant morbidity and healthcare costs. The effect of weather as a risk factor for the development of vaso-occlusive episodes (VOEs) has been previously studied, although with variable results. The aim of our retrospective, nationwide study was to determine the association between weather patterns and pediatric VOE and acute chest syndrome (ACS). Demographic and clinical data were obtained between 2015 and 2022 from the Pediatric Health Information System and merged with weather data from the National Climatic Data Center. We observed a higher incidence of VOE and ACS admissions during the colder months. Results also revealed a negative association between VOE admissions and average temperature, whereas a positive association was found for ACS admissions. Medical providers should continue to counsel patients with SCD to take appropriate precautions during cold weather.

Systematic review of emergency department management of vaso-occlusive episodes in adults with sickle cell disease

Abstract The objective of this systematic review was to characterize the management of vaso-occlusive episodes (VOEs) in adult patients with SCD in the emergency department (ED) via implementation of a protocol or pathway intended to improve patient care for VOE-related pain. A literature search was conducted spanning origin through May 31, 2023, using Embase, MEDLINE ALL, and International Pharmaceutical Abstracts databases. Primary literature reporting on adult patients with SCD in a SCD-specific pathway or protocol in an ED setting was included. Data extracted included report design characteristics, patient demographics, descriptors of the pathway/protocol, pain outcomes, and hospital length of stay. The Cochrane Risk of Bias 2.0 tool was used to assess risk-of-bias in randomized controlled trials (RCTs). The Risk of Bias for Non-Randomized Studies of Interventions was used to assess risk-of-bias in nonrandomized trials (NRTs). Certainty of evidence was assessed via the Grading of Recommendations, Assessment, Development, and Evaluations tool. Nine reports met eligibility criteria: 2 reports of 1 RCT and 7 observational NRTs. The RCT had low risk-of-bias; 5 NRTs had moderate risk-of-bias, 2 had serious risk-of-bias. Improvements in time to first opioid, pain scores, length of ED treatment time, overall treatment time (length of stay), and inpatient readmission improved with policies/protocols for the management of VOEs in the ED setting. These 5 outcomes had a moderate certainty of evidence. Institutions should consider implementing protocols or pathways to improve management of VOEs in the ED.

Plasma inflammatory and angiogenic protein profiling of patients with sickle cell disease.

In this study, we aimed to explore the inflammatory and angiogenic pathways in sickle cell disease (SCD). We used proximity extension assay technology (Olink) to measure 92 plasma proteins involved in inflammation and angiogenesis. Plasma samples were collected from 57 SCD patients (sickle cell anaemia/HbS-β0 thalassaemia-thalassaemia) in steady-state and 13 healthy ethnicity-matched healthy controls (HCs). From 15 patients, paired samples were collected during both steady-state and vaso-occlusive episodes (VOEs) and from 23 SCD patients longitudinal samples were collected before and after treatment with either voxelotor (n = 10), hydroxyurea (n = 8) or allogeneic haematopoietic stem-cell transplantation (n = 5). Fifty plasma proteins were differentially expressed in steady-state SCD patients as compared to HC. These included proteins involved in angiogenesis (i.e. ANGPT1, ANGPT2 and VEGFA), the IL-18 signalling pathway (i.e. IL-6, IL-10, IL-18), T-cell activation (i.e. LAG3, PDCD1) and natural killer (NK)-cell activation (CD244, NCR1, GZMB). While proteins involved in angiogenesis and the IL-18 signalling pathway were further upregulated during VOE, levels of several proteins involved in the IL-18 pathway, T-cell and NK-cell activation and angiogenesis, restored towards levels detected in HCs after curative or disease-modifying treatment. These findings might contribute to a better understanding of SCD pathophysiology and identifying potential new targets for therapeutic interventions.

PD54 Impact Of Experiencing Vaso-Occlusive Crisis In Patients With Sickle Cell Disease: Systematic Review And Meta-Analysis Of Prognostic Studies

IntroductionSickle cell disease (SCD) is characterized by recurrent painful ischemic vaso-occlusive episodes (VOEs). Acute episodes of pain, often termed sickle cell pain crises or vaso-occlusive crises (VOCs), are one of the most common and debilitating manifestations of SCD. Here we present a systematic review of 31 trials of 202,758 patients with SCD.Methods This study followed the guidelines of Riley et al. for conducting a systematic review and meta-analysis of prognostic factor studies and was reported according to PRISMA guidelines. Literature searches were conducted in the PubMed, Embase, and LILACS databases. The websites of the Annual Academy for Sickle Cell and Thalassemia Conferences, the European Hematology Association, and the American Society of Hematology were also searched. Additionally, manual searches were conducted in Google Scholar, Epistemonikos, and the reference lists of included studies. The searches were performed on 22 March 2023.Results In total, 31 studies were included in this systematic review. There was considerable heterogeneity in the definition of prognostic factors of interest across the included studies. Findings revealed a link between VOCs and reduced health-related quality of life (HRQoL), severe pain, and a high rate of hospitalization. Although VOCs were related to an increased mortality risk, the mortality rate remained relatively low, with acute chest syndrome being a common cause of death. Despite the study heterogeneity, consistent evidence highlighted the impact of VOCs on SCD-related hospitalizations (pooled hospitalization rate due to VOEs of 47%, 95% confidence Interval: 33, 61; 16 studies, 139,752 participants).ConclusionsThis study suggests that VOCs reduce HRQoL, cause severe pain, and lead to high rates of hospitalization in patients with SCD. Furthermore, VOEs were related to an increased mortality risk. Future research should prioritize more well-designed comparative prospective studies and standardization of the definition of VOCs. A better understanding of VOCs as a prognostic factor could enhance HRQoL, alleviate healthcare system burden, and inform more effective interventions for patients with SCD.

Lactated Ringer Instead of Normal Saline Solution for Sickle Cell Vaso-Occlusive Episodes.

According to this study.

Time Is Quality of Life (QoL): An Institutional Review of Emergency Department Management of Acute Vaso-Occlusive Episodes in Patients with Sickle Cell Disease

Time Is Quality of Life (QoL): An Institutional Review of Emergency Department Management of Acute Vaso-Occlusive Episodes in Patients with Sickle Cell Disease

Hemoglobin F% and Complete Blood Count Patterns in Two Independent Sickle Cell Anemia Cohorts from India & the US

Hemoglobin F% and Complete Blood Count Patterns in Two Independent Sickle Cell Anemia Cohorts from India & the US

Development of a Calculator to Determine Individualized Opioid Doses for Treatment of Vaso-Occlusive Episodes for Sickle Cell Disease in the Emergency Department

Development of a Calculator to Determine Individualized Opioid Doses for Treatment of Vaso-Occlusive Episodes for Sickle Cell Disease in the Emergency Department

Trends and hospital practice variation for analgesia for children with sickle cell disease with vaso-occlusive pain episodes: An 11-year analysis

Trends and hospital practice variation for analgesia for children with sickle cell disease with vaso-occlusive pain episodes: An 11-year analysis

Development, implementation, and acceptability of a bedside mindfulness intervention for adults with sickle cell disease

ABSTRACT Acute and chronic pain are the most frequent complications of sickle cell disease (SCD), often severely reducing quality of life and requiring management with long-term pharmacological interventions. A biopsychosocial approach conceptualizing pain in SCD as the result of complex biological, psychological, and social factors could facilitate targeted behavioral interventions. Mindfulness is one procedure for management of pain in individuals with chronic pain/illness. The goal of the current project was to design and implement a bedside mindfulness intervention to help patients with SCD enhance self-efficacy of pain management and reduce distress. As part of a quality improvement project in SCD clinics in a large health system, we developed a bedside mindfulness intervention to be provided during infusion sessions for patients presenting for acute vaso-occlusive episodes (VOE). The approach to development and implementation involved engagement of professionals working directly with patients. Concept planning meetings with these professionals along with qualitative patient and provider feedback informed feasibility, design, and intervention application. During a quantitative phase, patients completed validated surveys items on acceptability. Interview data (N = 11) supported patient interest in mindfulness skills and highlighted a need for tailored, person-centered interventions and non-pharmacological treatment strategies. On quantitative items, participants (N = 14) liked the intervention and agreed mindfulness skills would help manage disease-related distress. Following the interventions, participants reported increased mindfulness (p = .005). While preliminary, these results provide support for the continued development of evidence-based, mindfulness-oriented services to help individuals with SCD manage pain and other psychological difficulties.

Inpatient Management of Pain Episodes in Children with Sickle Cell Disease: A Review.

Sickle cell disease (SCD) is the most common hemoglobinopathy in the world. Sickle cell vaso-occlusive episodes (VOEs) are very painful acute events and the most common complication as well as reason for hospitalization. SCD pain is best evaluated holistically with a pain functional assessment to aid in focusing pain management on reducing pain in addition to improving function. Patients with SCD have long endured structural racism and negative implicit bias surrounding the management of pain. Thus, it is important to approach the management of inpatient pain systematically with the use of multi-modal medications and nonpharmacologic treatments. Furthermore, equitable pain management care can be better achieved with standardized pain plans for an entire system and individualized pain plans for patients who fall outside the scope of the standardized pain plans. In this article, we discuss the best practices to manage SCD VOEs during an inpatient hospitalization.

Lactated Ringer vs Normal Saline Solution During Sickle Cell Vaso-Occlusive Episodes

Sickle cell disease (SCD), a clinically heterogenous genetic hemoglobinopathy, is characterized by painful vaso-occlusive episodes (VOEs) that can require hospitalization. Patients admitted with VOEs are often initially resuscitated with normal saline (NS) to improve concurrent hypovolemia, despite preclinical evidence that NS may promote erythrocyte sickling. The comparative effectiveness of alternative volume-expanding fluids (eg, lactated Ringer [LR]) for resuscitation during VOEs is unclear. To compare the effectiveness of LR to NS fluid resuscitation in patients with SCD and VOEs. This multicenter cohort study and target trial emulation included inpatient adults with SCD VOEs who received either LR or NS on hospital day 1. The Premier PINC AI database (2016-2022), a multicenter clinical database including approximately 25% of US hospitalizations was used. The analysis took place between October 6, 2023, and June 20, 2024. Receipt of LR (intervention) or NS (control) on hospital day 1. The primary outcome was hospital-free days (HFDs) by day 30. Targeted maximum likelihood estimation was used to calculate marginal effect estimates. Heterogeneity of treatment effect was explored in subgroups. A total of 55 574 patient encounters where LR (n = 3495) or NS (n = 52 079) was administered on hospital day 1 were included; the median (IQR) age was 30 (25-37) years. Patients who received LR had more HFDs compared with those who received NS (marginal mean difference, 0.4; 95% CI, 0.1-0.6 days). Patients who received LR also had shorter hospital lengths of stay (marginal mean difference, -0.4; 95% CI, -0.7 to -0.1 days) and lower risk of 30-day readmission (marginal risk difference, -5.8%; 95% CI, -9.8% to -1.8%). Differences in HFDs between LR and NS were heterogenous based on fluid volume received: among patients who received less than 2 L, there was no difference in LR vs NS; among those who received 2 or more L, LR was superior to NS. This cohort study found that, compared with NS, LR had a small but significant improvement in HFDs and secondary outcomes including 30-day readmission. These results suggest that, among patients with VOEs in whom clinicians plan to give volume resuscitation fluids on hospital admission, LR should be preferred over NS.

Identification of genetic variants associated with clinical features of sickle cell disease

Sickle cell disease (SCD) is an inherited blood disorder marked by homozygosity of hemoglobin S, which is a defective hemoglobin caused by a missense mutation in the β-globin gene. However, clinical phenotypes of SCD vary among patients. To investigate genetic variants associated with various clinical phenotypes of SCD, we genotyped DNA samples from 520 SCD subjects and used a genome-wide association study (GWAS) approach to identify genetic variants associated with phenotypic features of SCD. For HbF levels, the previously reported 2p16.1 locus (BCL11A) reached genome significance (rs1427407, P = 8.58 × 10–10) in our GWAS as expected. In addition, we found a new genome-wide significance locus at 15q14 (rs8182015, P = 2.07 × 10–8) near gene EMC7. GWAS of acute chest syndrome (ACS) detected a locus (rs79915189, P = 3.70 × 10–8) near gene IDH2 at 15q26.1. The SNP, rs79915189, is also an expression quantitative trait locus (eQTL) of IDH2 in multiple tissues. For vasoocclusive episode (VOE), GWAS detected multiple significant signals at 2p25.1 (rs62118798, P = 4.27 × 10–8), 15q26.1 (rs62020555, P = 2.04 × 10–9) and 15q26.3 (rs117797325, P = 4.63 × 10–8). Our findings provide novel insights into the genetic mechanisms of SCD suggesting that common genetic variants play an important role in the presentation of the clinical phenotypes of patients with SCD.

Comparison of Measures of Pain Intensity During Sickle Cell Disease Vaso-Occlusive Episodes

Comparison of Measures of Pain Intensity During Sickle Cell Disease Vaso-Occlusive Episodes