scholarly journals Assessing the Safety and Efficacy of Converting Adults with Sickle Cell Disease from Full Agonist Opioids to Buprenorphine

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 856-856 ◽  
Author(s):  
Mandy David ◽  
Christopher Carroll ◽  
Ashley Lauriello ◽  
Benjamin Salzberg ◽  
Sophie Lanzkron
Keyword(s):  
Sickle Cell Disease ◽  
Acute Care ◽  
Sickle Cell ◽  
Research Funding ◽  
Opioid Therapy ◽  
Cell Disease ◽  
Chronic Opioid Therapy ◽  
Full Agonist ◽  
Post Induction ◽  
Disease Modifying Therapy

Abstract Background: The management of pain in adults with sickle cell disease (SCD) is complex, with the intermingling of both acute vaso-occlusive events and chronic daily pain. Sixty percent of adults with SCD suffer with every day chronic pain. In patients with frequent acute visits we use aggressive disease modifying therapy to decrease the risk of VOC yet there remains a subset of patients who continue to have frequent acute visits for pain. In addition, there are patients maintained on high doses of oral opioids as outpatients who continue to have high levels of daily pain. There is little data that escalating doses of opioids is associated with benefit, yet significant data to support that higher doses are associated with harms. We consider these to be cases of opioid failure. Identifying therapies for these patients that improve quality of life is essential. Buprenorphine is a partial mu opioid receptor agonist and kappa antagonist, and has a very high affinity for the mu receptors, with an elimination half-life of 28-37 hours for the sublingual administration. The reduced risk of overdose, lower risk for misuse, diminished withdrawal symptoms, and blunting of opioid craving make it an appealing alternative to full opioid agonists in a subset of patients with SCD who continue to have significant pain or are unable to wean off of ineffective opioid therapy. The purpose of this report is to describe our experience converting patients with SCD and chronic pain from chronic opioid therapy to buprenorphine. Methods: Routine clinical care in our clinic includes offering buprenorphine transition to patients on chronic opioid therapy with numerous acute care visits despite the use of disease modifying therapy; or patients on chronic opioid therapy reporting significant ongoing pain. Patients are typically weaned to lower opioid doses (goal 90 oral morphine equivalents) prior to the planned induction with buprenorphine. Once patients are at the goal dose, they are asked to hold opioids for 12-24 hours prior to presentation so that they are in at least mild opioid withdrawal prior to their first dose of buprenorphine to avoid precipitated withdrawal. The patient is assessed with the Clinical Opiate Withdrawal Scale (COWs) and if their score is 5 or higher they are administered their first dose of sublingual buprenorphine. If COWs scores are less than 5, buprenorphine is not initiated and the subject is asked to return the following day or earlier if withdrawal symptoms begin. Patients are reassessed with the COWs and dosed with buprenorphine hourly until withdrawal has ceased. The dose needed to minimize withdrawal is considered the working total daily dose. Patients are sent home and return the next day to start their once daily dose of buprenorphine. Urine toxicology testing is done the day of planned induction. Data on acute visits 6 months prior and 6 months post induction and on complications associated with induction were pulled from the electronic health record. Results: 21 patients have been converted from full agonist opioids to buprenorphine from 3/2015-6/1/2018. The average age of the patients at the time of induction was 36.1 years (SD 9.1), 62% were female. Sixteen (76 %) of the patients had sickle cell anemia, the remainder had variant genotypes. The mean dose (in morphine equivalents) of full agonist opioid that patients were on prior to weaning of opioids was 196.8 mg (SD 222.7) and just prior to induction was 85 mg (SD 70 mg) with a range of 11.4 to 315 mg. Seventeen patients tolerated the induction without any complications, 2 patients had abdominal cramps but were successfully converted, 2 patients has adverse reactions (1 had numbness of tongue and 1 with worsening of asthma) and buprenorphine was stopped. Of the 19 patients successfully converted, two chose to stop buprenorphine and resume taking full opioid agonists. For the 13 patients with 6 months of follow-up post induction, the median number of acute care visits prior to induction was 12.5 and post was 4.0 (Figure). Conclusions: Adults with sickle cell disease on chronic full agonist opioid therapy can be safely converted to buprenorphine. Acute care utilization has dropped significantly for patients post induction. Assessment of patient reported outcomes such as quality of life and pain interference are being collected. Buprenorphine appears to be a safe and effective medication in the management of pain in adults with SCD. Figure. Figure. Disclosures Lanzkron: PCORI: Research Funding; GBT: Research Funding; Prolong: Research Funding; Pfizer: Research Funding; selexys: Research Funding; NHLBI: Research Funding; HRSA: Research Funding; Ironwood: Research Funding.

(234) Chronic opioid therapy is more strongly associated with central sensitization in sickle cell disease than clinical pain

2015 ◽  
Vol 16 (4) ◽  
pp. S34
Author(s):  
P. Carroll ◽  
C. Campbell ◽  
G. Moscou-Jackson ◽  
P. Finan ◽  
S. Lanzkron ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Central Sensitization ◽  
Opioid Therapy ◽  
Cell Disease ◽  
Chronic Opioid Therapy ◽  
Clinical Pain

scholarly journals Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

2016 ◽  
Vol 51 (1) ◽  
pp. S69-S77 ◽  
Author(s):  
C. Patrick Carroll ◽  
Sophie Lanzkron ◽  
Carlton Haywood ◽  
Kasey Kiley ◽  
Megan Pejsa ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Central Sensitization ◽  
Opioid Therapy ◽  
Cell Disease ◽  
Chronic Opioid Therapy

scholarly journals Implementation of a Standard Order Set at a Sickle Cell Acute Care Observation Unit

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3396-3396
Author(s):  
Renee Cheng ◽  
Rishi Patel ◽  
Sandra Kang ◽  
Frances Tian ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Pain Management ◽  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Acute Care ◽  
Sickle Cell ◽  
Research Funding ◽  
Mixed Effects ◽  
Data Sets ◽  
Cell Disease ◽  
Data Set

I NTRODUCTION: Acute painful vaso-occlusive crises (VOC) in sickle cell disease (SCD) are the leading cause of emergency department (ED) encounters and frequent hospital admissions. For patients presenting with an uncomplicated VOC, acute care observation units (ACOU) have previously been shown to reduce admission rates and length of stay. We wished to evaluate if implementing a standardized acute care order set (ACOS) at the University of Illinois Hospital Sickle Cell ACOU would decrease the time to first dose of analgesic medication, inpatient hospital stays, and subsequent admissions to the ACOU. METHODS: The ACOS includes standard orders for laboratory tests to monitor severity of sickle cell hemolysis, intravenous fluids, and analgesic medications including opioids. We conducted a retrospective analysis to evaluate if the ACOS enhanced workflow and improved the timeliness of treatment in patients experiencing a VOC. The ACOS was created in April 2017 and we compiled data from the three months before (January-March 2017) and after (May-July 2017) ACOS creation. We collected data on the time it took to administer the first opioid dose, admission rate, length of stay, number of acute care visits, ED visits, and inpatient hospitalizations in a three-month span, and demographics including variations in age, gender, and sickle cell disease genotype. Patient data was collected from a pharmacy-generated list of patients who received narcotics in the ACOU during the aforementioned time period. We analyzed the effect of the ACOS on the aforementioned variables. A mixed effects linear model was used to compare time to first dose of opioids and length of stay between data sets. A mixed effects logistic model was used for binary outcomes. Covariates of age (years), gender, and severity of sickle cell hemoglobin genotype (severe: HbSS, HbS beta0 thalassemia; mild: HbSC, HbS beta+ thalassemia) were included in the models. Statistical analyses were carried out in R version 3.4.3. DISCUSSION: The pre-ACOS data set contains 291 patient encounters for 76 patients with a median age of 37 years (interquartile range [IQR], 30-47 years), 66% female, and 71% with severe genotypes. The post-ACOS data set contained 289 patient encounters for 80 patients with a median age of 32 years (IQR, 27-45 years), 80% female, and 73% with severe genotypes. Implementation of an ACOS was associated with decreased time to pain management by 3.7 minutes (p=0.077) in patients presenting with uncomplicated VOC and with fewer repeat visits to the ACOU in the studied 3-month period [OR 0.35 (95% CI 0.13-1.00), p=0.049]. The median number of opiate doses received by patients in both data sets was 3. Using 3 as a cutoff, the implementation of the ACOS was also associated with more patients receiving >3 doses of opiates [OR=1.84 (95% CI 1.05-3.19), p = 0.033]. We demonstrate that in SCD patients experiencing VOC, a standardized ACOS was associated with a trend to reducing time to receiving pain management, with increased total opioid doses during the ACOU admission (suggesting better pain control), and subsequently with a statistically significant reduction in the number of repeat ACOU visits in the studied 3-month period. We have shown that a standardized ACOS that streamlines workflow in an ACOU may play an important role in delivering timely and quality care to patients with SCD. Disclosures Gordeuk: Pfizer: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Honoraria, Research Funding; Modus Therapeutics: Consultancy, Honoraria; Ironwood: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Imara: Research Funding; Inctye: Research Funding; Inctye: Research Funding; Pfizer: Research Funding; Emmaus: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria, Research Funding; Ironwood: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Imara: Research Funding; Modus Therapeutics: Consultancy, Honoraria.

Acute Care Utilization Is More Common in Patients with Sickle Cell Disease Who Have Chronic Complications and Chronic Pain: A Preliminary Report from the Escaped Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2490-2490 ◽  
Author(s):  
Sophie Lanzkron ◽  
Carlton Haywood ◽  
Jane A Little ◽  
Joshua Field ◽  
Joseph Ryan Shows ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sickle Cell Disease ◽  
Acute Care ◽  
Sickle Cell ◽  
Research Funding ◽  
Symptom Burden ◽  
Care Utilization ◽  
Cell Disease ◽  
Chronic Complications

Abstract Background: We undertook a large multisite observational study collecting prospective data on health care utilization of patients with sickle cell disease (SCD). No prospective examination of symptom burden has been undertaken in SCD since the Cooperative Study of Sickle Cell Disease, and none in the modern era, since the widespread adoption of hydroxyurea therapy. The ESCAPED trial aims to compare patient centered outcomes following management of acute painful vaso-occlusive (VOC) events in the emergency department or in the infusion center. Here, we examine acute care utilization patterns in the first 223 subjects who have completed at least 6 months of follow-up and test determinants of utilization. Methods: This is an ongoing, prospective cohort study that is recruiting across four sites (Baltimore, Cleveland, Milwaukee, and Baton Rouge). 500 adults with SCD who live in proximity to one of the study sites are being recruited and followed for 18 months. Data from visits for all acute, uncomplicated VOC are collected by chart review and patient interview. To ensure that acute visits are not missed, subjects are contacted on a monthly basis and where available statewide health information exchanges are queried. We tested for associations between subject characteristics upon enrollment and the number of acute visits during follow up using Poisson regression. Results: The average length of follow-up to date is 9.1 months with a range of 6.1-14.2 months for the 223 subjects who have been enrolled for at least 6 months. The mean number of acute visits per month for uncomplicated VOC by the cohort was 0.65 (SD 0.87) with a median of 0.35, minimum of 0 and maximum of 5. 43 subjects have had no acute visits. 59% of the cohort are female, the mean age is 35.6 (SD 12.1). 74.3% have sickle cell anemia, 42% are employed and 52% reported having chronic pain. In a multivariate model, factors associated with an independent decrease in likelihood of an acute visit were increasing age, a history of leg ulcers, graduating high school and being employed, while an increase in likelihood of an acute visit was associated with chronic complications (kidney disease, retinopathy, stroke, and avascular necrosis) and chronic pain. Conclusions: In this cohort, chronic complications like renal disease and AVN are associated with increased acute care visits. The association of chronic pain as an independent risk factor for acute visits, while intuitive, suggests that understanding and managing chronic pain may be central to mitigating pain and decreasing the need for acute care visits in the long term. The prevalence of chronic pain is high in this cohort, which likely well represents the contemporary US sickle cell community. The development of therapeutic strategies that address this significant complication of SCD are imperative if we are to both decrease symptom burden and the need for health care utilization in this population. Disclosures Lanzkron: NKT therapeutics: Research Funding; Prolong: Research Funding; Pfizer: Research Funding; Selexys: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; GBT: Consultancy. Haywood:PCORI: Research Funding; NHLBI: Research Funding. Little:PCORI: Research Funding. Field:PCORI: Research Funding; NKT Therapeutics: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding. Shows:PCORI: Employment, Research Funding. Segal:PCORI funded: Research Funding. Saheed:PCORI: Research Funding. Robertson:PCORI: Research Funding. Proudford:PCORI: Research Funding. Kincaid:PCORI funded: Research Funding. Burgess:PCORI: Research Funding. Green:PCORI: Research Funding. Wang:PCORI: Research Funding. Seufert:PCORI: Research Funding. Brooks:PCORI: Research Funding. Griffin:PCORI: Research Funding. Piehet:PCORI: Research Funding. Frymark:PCORI: Research Funding. Varadhan:PCORI: Research Funding.

scholarly journals Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease: A National Alliance of Sickle Cell Centers Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3113-3113
Author(s):  
Julie Kanter ◽  
Gerhard Hellemann ◽  
Alice J. Cohen ◽  
Deepa Manwani ◽  
Modupe Idowu ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Acute Care ◽  
Sickle Cell ◽  
Real World ◽  
Research Funding ◽  
Cell Disease ◽  
Advisory Committees ◽  
Level Data ◽  
National Alliance

Abstract Background: Vaso-occlusive crises (VOC) are the most common acute complication of sickle cell disease (SCD). Crizanlizumab, an anti-P-selectin monoclonal antibody, is an FDA-approved disease-modifying therapy (DMT) for SCD patients (pts) aged ≥16 yrs to reduce the frequency of VOC. To better understand its use and impact, the National Alliance for Sickle Cell Centers (NASCC) conducted a retrospective study of pts prescribed crizanlizumab from 11/2019-6/30/2021. NASCC is a non-profit organization formed to support SCD centers in delivering quality comprehensive care by setting and adopting specific standards and advocating for improved health outcomes in SCD. This study describes the largest real-world cohort of pts treated with crizanlizumab. Methods: This is a two-part study. Part 1 was to evaluate NASCC center crizanlizumab practice and to summarize data on insurance approval and the frequency of drug discontinuation. Part 2 includes pt level data to evaluate reasons for discontinuation and acute care utilization pre and post therapy. Acute care use includes day hospital/infusion, emergency department visits, and hospitalizations for VOC (excluding COVID-19). The index date for each pt is defined as the 1st crizanlizumab infusion date. Chart review (electronic health records) was used to identify all acute care visits 12 months pre-index and ≤12 months post index. Acute care data will be analyzed in aggregate. Evaluation of center-specific use of crizanlizumab, time to initial site level formulary approval and drug discontinuation were analyzed. Pt level data collection is ongoing to include sufficient time post index date. VOC characteristics will be summarized using medians, median differences (pre/post treatment), and 95% confidence intervals. Additional evaluation of effectiveness of crizanlizumab will include analysis based on number of doses received, pre-treatment VOC burden, concomitant hydroxyurea (HU) use and genotype. Results: Data includes pts prescribed crizanlizumab at 11 NASCC centers. Site- formulary approvals to use crizanlizumab varied from 12/2019-12/2020. As a result, the 1st pt to receive treatment at each site varied from 1/15/2020-1/20/2021. Mean time from site-level approval to first infusion was 77 days (range: 0-394). Over 50% of sites received insurance denials mainly due to "insufficient medical necessity" or "medication not covered by the prescription plan." Sites were able to successfully appeal denials for 71% of pts (Table 1). Treatment Delivery: Each site gives infusions over 30 minutes and the majority (64%) do not use pre-medication unless pts had reactions. Some sites use diphenhydramine/acetaminophen (3) or normal saline and ketorolac (1). All sites prescribe crizanlizumab to pts of all SCD genotypes. Pts Treated: 297 pts were prescribed crizanlizumab of whom 238 received ≥ 1 infusion. There was variation in number of pts/site (range 6-73, mean 21) due to time to site-level approval, insurance and pt population. Of these 238, 75 pts (32%) discontinued treatment (0-17 pts/site). Sites reported pts perceived lack of improvement or feeling their overall pain was increased, transportation issues and infusion related reactions (IRRs) characterized by pain as some of the reasons for discontinuation. Evaluation of real-world efficacy measured by changes in acute care utilization, including sub-analysis by genotype, pre-treatment VOC burden and concomitant HU use, are pending sample size dependent feasibility. Discussion: This is the first multi-center real-world analysis of crizanlizumab. Findings demonstrate some insurance barriers to therapy. The majority of pts who initiated crizanlizumab have remained on therapy; however, 1/3 of pts had lack of effect or barriers to care. Pt level data will include characteristics related to treatment failure or IRR. Improving the understanding of phenotype-specific response to novel therapies is essential in SCD. Conclusion: Post-approval therapies for rare diseases must undergo real-world evaluation to ensure study results translate to the community. NASCC uses defined criteria for multidisciplinary care for Alliance inclusion and findings reflect the use of DMT in such centers. This is the first NASCC study of DMT in SCD. Part 2 of the study will give early insights into the effectiveness of crizanlizumab; long term follow-up is needed for a full understanding of its utility in SCD. Figure 1 Figure 1. Disclosures Kanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy. Manwani: Novartis: Consultancy. Idowu: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Forma Therapeutics, Inc.: Research Funding; Ironwood: Research Funding. Treadwell: National Alliance of Sickle Cell Centers: Other: Early Evaluation of the Use of Crizanlizumab in Sickle Cell Disease. Clay: GBT: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Little: Hemex Health, Inc.: Patents & Royalties; Biochip Labs: Patents & Royalties. Desai: Global Blood Therapeutics: Honoraria, Research Funding; Novartis: Research Funding, Speakers Bureau; Pfizer: Other: Publication Fee, Research Funding; Forma: Consultancy; Foundation for Sickle Cell Research: Honoraria. Lanzkron: Shire: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Bluebird Bio: Consultancy; Teva: Current holder of individual stocks in a privately-held company; Novo Nordisk: Consultancy; GBT: Research Funding; Imara: Research Funding; CSL Behring: Research Funding; Novartis: Research Funding.

scholarly journals Effect of Chronic Opioid Therapy on Pain and Survival in a Mouse Model of Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 726-726
Author(s):  
Varun Sagi ◽  
Huy Tran ◽  
Waogwende Leonce Song-Naba ◽  
Ying WANG ◽  
Aditya M Mittal ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Opioid Therapy ◽  
Cell Disease ◽  
Opioid Use ◽  
Chronic Opioid Therapy ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Pain Characteristics

Abstract Pain is one of the major comorbidities of sickle cell disease (SCD) requiring chronic opioid therapy (COT). However, COT has been associated with reduced survival and opioid-induced hyperalgesia (OIH), which can exacerbate the chronic pain and increased mortality already inherent to SCD. It is challenging to examine pain, opioid use and survival in populations with SCD due to significant heterogeneity in multiple clinicopathologic factors. To determine the effect of COT we used transgenic HbSS BERK sickle mice, which show pain characteristics similar to those observed in patients with SCD, including sensitivity to thermal and mechanical stimuli, increased opioid requirement, and higher levels of circulating substance P and tryptase (Tran et al., Blood 2017). Additionally, similar to female patients with SCD, female BERK sickle mice show more pain than males. Therefore, we performed a randomized double-blind placebo-controlled trial to examine the effect of COT on pain and survival in female homozygous HbSS BERK (sickle) and HbAA BERK (control) mice, expressing >99% human sickle hemoglobin and normal human hemoglobin A, respectively. Mice were injected subcutaneously each day with either morphine sulfate at a starting dose of 20 mg/kg, which was increased to 25 mg/kg, 30 mg/kg, 35 mg/kg, and 40 mg/kg after weeks 12, 18, 28, 30, and 38 respectively or placebo (equal volume of saline) until the end of survival. Dose of morphine was selected based on the effective analgesic dose for these mice (Kohli et al., Blood 2010). Mechanical-, thermal- (heat and cold), and musculoskeletal/deep hyperalgesia were analyzed in all mice biweekly before and after drug treatments. We used Kaplan-Meier and log-rank test with Sidak correction for survival; 2-way repeated measures analysis of variance with Bonferroni's correction to compare hyperalgesia between time points among control and sickle mice and Cox proportional-hazards regression analysis for the association of hyperalgesia with survival. We observed significantly decreased survival of saline-treated sickle mice compared to saline-treated control mice (P = 0.0009). Compared to saline, morphine treatment led to a significant decrease in survival in control mice (P = 0.035) but not in sickle mice (P > 0.05). Furthermore, we did not observe an association between hyperalgesia and survival in either control or sickle mice. However, we discerned a significant increase in mechanical, cold, and heat hyperalgesia in control mice after 4 weeks of morphine treatment (P < 0.02, compared to day '0') which continued to increase up to 12 weeks (P <0.05 compared to week 4). Similarly, in sickle mice we observed an increase in mechanical hyperalgesia after 4 weeks (P <0.02, compared to day '0') of morphine treatment which continued to increase up to 12 weeks (P < 0.0001). These data suggest COT leads to OIH in both control and sickle mice. It is noteworthy that morphine treatment continued to show an analgesic effect over the course of 12 weeks in spite of an increase in hyperalgesia in both groups of mice. Thus, mice did not develop tolerance to morphine analgesia. Since mice were treated under uniform conditions, the effect of chronic morphine treatment could be observed without any confounding factors. Our findings in control mice recapitulate the clinical observations that COT is associated with reduced lifespan in non-sickle patients. COT lead to OIH in sickle mice but provided analgesia without causing tolerance or reducing survival. OIH may contribute may exacerbate a vicious cycle of chronic pain and opioid use in SCD. Differences exist between humans and mice including morphine metabolism between the two but due to several similarities of HbSS BERK sickle mice with clinical pain characteristics and biology, these observations have a significant translational potential following clinical trials for optimizing the treatment of pain in SCD. These data highlight the critical need to develop analgesic strategies devoid of OIH. Disclosures Gupta: Tau tona: Consultancy; Novartis: Honoraria.

scholarly journals COVID Symptoms and COVID Anxiety in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Wally R Smith ◽  
Benjamin Jaworowski ◽  
Shirley Johnson ◽  
Thokozeni Lipato ◽  
Daniel M Sop
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Telephone Survey ◽  
Cell Disease ◽  
Weighted Mean ◽  
The Us ◽  
Associated Symptoms ◽  
At Home

Background Even before the US upswing of the current COVID pandemic, the number of sickle cell disease (SCD) patients coming to hospitals and EDs appeared to fall drastically. This happened despite SCD patients having often been heavy utilizers of the ED and hospital for their iconic vaso-occlusive crises (VOC). Though ambulatory SCD clinics quick converted largely to telehealth in order to comply with stay-at-home orders designed to suppress person-to-person transmission, some SCD patients appeared to avoid care, delay care, or refuse doctors' invitations for care. Presumably patients did so out of COVID fears, but this has not been confirmed in the literature. Further, whether these patients had COVID symptoms but stayed at home has not been studied. As part of quality improvement (QI) to conduct COVID surveillance in an adult sickle cell program, we sought to explain and predict SCD health care utilization patterns we were observing, as well as to determine urgent physical and mental health needs of patients who appeared to be avoiding care. Methods Fifteen staff in the Adult Sickle Cell Medical Home at Virginia Commonwealth University, a large urban academic medical center, conducted a telephone survey ("wellness check"was used when we talked to patients) of all known adults with SCD over 19 days in 2020. A staff member confirmed the patient had SCD, asked permission to proceed, then asked about symptoms consistent with COVID-19. At the end of the telephone survey, respondents wer invited to complete an email survey of sickle cell and COVID-19 utilization attitudes (19-33 items, depending on the response pattern, either drawn from the National Health Interview Survey, from the Adult Sickle Cell Quality of Life Measurement quality of care survey, or drafted by the authors), the Sickle Cell Stress Survey-Adult (SCSS-A, a 10-item previously validated survey), and anxiety and depression (PHQ9 of the PRIME-MD). Results Of 622 adults approached by phone call, 353 responded to the following yes/no screening questions regarding the prior 14 days: fever over 100 F 0/353 (0.00%); cough 3/353(0.01%); difficulty breathing 0/353(0.00%); unexplained shortness of breath 2/353(0.01%); sore throat 2/353 (0.01%); unexplained muscle soreness 2/353(0.01%);contact with anyone who tested positive for COVID-19 2/353(0.01%); testing for COVID 19 6/353(0.02%). For QI purposes, we set a threshold of three or more COVID-associated symptoms or the presence of fever as criteria requiring intense telephone or in-person staff monitoring for the following week. Only three patients met criteria. A total of 219/353 had email surveys sent. Of 63 patients (28.8%) who returned email surveys by June 10, 2020, 35.9% had already managed a "pain attack" at home 4 or more times in the prior 12 months, and 45.5% of these said their bad ER experiences were very or somewhat important in that decision. In the prior 14 days, although 30/64 reported a crisis for at least one day, only 4/64 had visited the Emergency Department for pain. On a 0-10 scale, 21/61 patients endorsed "0" for worry that they would be COVID-infected by going for medical care (weighted mean 3.9), but 18/59 endorsed "10" for worry they were more at risk of COVID because of SCD (weighted mean 6.31), and 22/60 endorsed "10" for worry they would fare worse than others if COVID infected (weighted mean 6.97). Many patients forwent "needed" care (16/62) or delayed "needed" care by at least a day (36/61). Eleven patients met criteria for moderately severe to severe depression on the PHQ-9, and 28/63 somewhat or strongly agreed with the statement "death is always on the back of my mind" on the SCSS-A. Conclusions In adolescents and adults with SCD, many were already reticent to come to the ED for pain, but a significant portion reported delays or avoidance of needed care during the early stages of the US COVID pandemic, and few reported using the ED despite over half reporting at least one crisis day in 14. Patients nonetheless reported very few COVID-associated symptoms. Fears of COVID infection/susceptibility may limit visits for needed sickle cell care among adults. Acknowledgements: Mica Ferlis RN, FNP, Caitlin McManus, RN, FNP, Emily Sushko, RN, FNP, Justin West, RN, Kate Osborne, RN, Stefani Vaughan-Sams, Marla Brannon, BS, Nakeiya Williams, BS Disclosures Smith: GlycoMimetics, Inc.: Consultancy; Emmaeus Pharmaceuticals, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Health Resources and Services Administration: Other: Investigator, Research Funding; Incyte: Other: Investigator; Pfizer: Consultancy; Ironwood: Consultancy; Novo Nordisk: Consultancy; Imara: Research Funding; Shire: Research Funding.

scholarly journals Clinical and Biomarker Predictors for Avascular Necrosis in Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3091-3091
Author(s):  
Michael Rabaza ◽  
Maria Armila Ruiz ◽  
Liana Posch ◽  
Faiz Ahmed Hussain ◽  
Franklin Njoku ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Research Funding ◽  
Medical Attention ◽  
Cell Disease ◽  
Advisory Committees ◽  
Early Management

Abstract Introduction Sickle cell disease (SCD) affects 1 in 365 African Americans and approximately 25 million people world-wide. A common skeletal system complication is avascular necrosis (AVN), which can cause substantial pain and a reduced quality of life. While early management of AVN is focused on increasing range of motion with physical therapy and pain relief, there are no clear predictors for who is more likely to develop AVN and earlier institution of these preventive measure could help decrease disease progression. Vascular endothelial growth factor (VEGF) is a biomarker of endothelial injury and may indicate reduced vascular supply to the femoral or humeral head. Here we describe potential risk factors and biologic pathways for AVN in SCD, as understanding these may lead to improvements in future monitoring, early detection, and early intervention practices. Methods We investigated clinical and laboratory risk factors associated with AVN in a cohort of 435 SCD patients from our center. Blood samples, clinical, and laboratory data were collected at the time of enrollment during a clinic visit. Genotyping for alpha thalassemia was performed by PCR and the serum concentration of VEGF was measured by ELISA. AVN status was confirmed by review of the medical record and available imaging. We conducted a cross-sectional analysis comparing categorical and linear variables by AVN status using the chi-square and Kruskal-Wallis test, respectively. The independent association of the clinical and laboratory variables with AVN status was determined by logistic regression analysis. The initial model included variables with a P-value &lt; 0.1 on univariate analysis and the final model was ascertained by stepwise forward and backward selection. Median values and interquartile range (IQR) are provided. Results The median age of the cohort was 32 (IQR, 24 - 43) years, 57% (250/435) were female, and 46% (198/435) were on hydroxyurea. AVN was observed in 34% (149/435) of SCD patients. SCD patients with AVN were older, had more frequent vaso-occlusive crises requiring medical attention, and had a higher body mass index (Table I) (P ≤ 0.002). We measured VEGF in 241 of the SCD patients with serum samples available at the time of enrolment. Serum VEGF concentrations trended higher in SCD patients with versus without AVN (420 vs. 359 pg/mL, respectively; P = 0.078). In the multivariate analysis model, AVN was independently associated with increased number of vaso-occlusive crises (OR 1.1, 95% CI: 1.0 - 1.14; P = 0.02), AST concentration (natural log OR 0.5, 95% CI: 0.2 - 0.9; P = 0.03), VEGF concentration (natural log OR 1.4, 95% CI: 1.0 - 1.9; P = 0.047), and tobacco use (OR 1.9, 95% CI: 0.9 - 3.7; P = 0.078). Discussion In conclusion, we demonstrate a high prevalence of AVN in an adult cohort of SCD patients. The presence of AVN was independently associated with a greater frequency of vaso-occlusive pain episodes, which may demonstrate a shared pathophysiology between AVN and vaso-occlusion that merits further investigation. We demonstrate that serum VEGF concentrations are higher in SCD patients with AVN and may be a clinical tool to identify those at high-risk and for earlier intervention for this complication. Figure 1 Figure 1. Disclosures Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Alkaline Phosphatase Is Associated with Red Cell Alloimmunization in the Pulmonary Hypertension and Hypoxic Response (PUSH) Sickle Cell Disease Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Victoria Brooks ◽  
Oluwalonimi Adebowale ◽  
Victor R. Gordeuk ◽  
Sergei Nekhai ◽  
James G. Taylor
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Severe Disease ◽  
Case Control ◽  
Red Cell ◽  
Cell Disease ◽  
History Of

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with &gt;10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.

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