Sickle Cell Pain Crisis Research Articles

Crizanlizumab 5.0 Mg/Kg Increased the Time to First on-Treatment Sickle Cell Pain Crisis: A Subgroup Analysis of the Phase II Sustain Study

Abstract Background: In the 52-week SUSTAIN study, which compared the P-selectin inhibitor crizanlizumab with placebo, crizanlizumab 5.0 mg/kg significantly reduced the frequency of sickle cell pain crises (SCPCs) versus placebo (1.6 vs 3.0, P=0.01) and increased the time to first on-treatment SCPC (4.1 vs 1.4 months, P=0.001) in patients with sickle cell disease (SCD) (Ataga KI et al. N Engl J Med 2017;376:429-39). Due to heterogeneity in disease severity and differences in medications used for the treatment of SCD and various other factors, treatment responses may vary between individuals with SCD. Differences in the response to crizanlizumab observed in defined subgroups of patients are of interest to increase understanding of this treatment, and the role of P-selectin in SCD. Aims: This post hoc analysis evaluated the time to first SCPC in subgroups of the SUSTAIN study population to further assess the efficacy of crizanlizumab 5.0 mg/kg and differences in treatment response between those subgroups. Methods: SUSTAIN was a randomized, double-blind, placebo-controlled, Phase II study (NCT01895361). Patients aged 16-65 years with SCD (HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia or other genotype) were included if they had experienced 2-10 SCPC events in the previous 12 months. Concomitant use of hydroxyurea (HU) was permitted if the patient had been using it for ≥6 months and at a stable dose for ≥3 months. Patients were randomized 1:1:1 to receive intravenous crizanlizumab 5.0 mg/kg, 2.5 mg/kg or placebo; however, this abstract focuses on the 5.0 mg/kg dose of crizanlizumab versus placebo. Study treatments were administered on days 1 and 15, then every 4 weeks to week 50; the final study visit of the treatment phase was at week 52, with an additional follow-up visit at week 56. The median time to first SCPC after the first dose of study treatment was summarized for patients treated with crizanlizumab 5.0 mg/kg or placebo in the following subgroups: 2-4 or 5-10 SCPC events in the previous 12 months; HbSS or non-HbSS genotype; and HU use (yes or no) at baseline. Hazard ratios (HRs) for crizanlizumab 5.0 mg/kg versus placebo were calculated based on Cox regression analysis, with treatment as a covariate. Results: 67 patients in the intent-to-treat population received crizanlizumab 5.0 mg/kg and 65 received placebo. Overall, more patients who had experienced 2-4 SCPCs (63% in both groups) than 5-10 SCPCs (37% in both groups) in the previous year were enrolled. HbSS was the most common genotype (crizanlizumab 5.0 mg/kg: 70%; placebo: 72%), and more than half of patients were taking HU at baseline (crizanlizumab 5.0 mg/kg: 63%; placebo: 62%). In almost all the subpopulations evaluated, crizanlizumab 5.0 mg/kg significantly (P Conclusions: Treatment with crizanlizumab 5.0 mg/kg significantly delayed the time to first on-treatment SCPC in adults living with SCD compared with placebo in most of the subpopulations investigated, including patients with the HbSS genotype, suggesting a potential for disease modification. Crizanlizumab 5.0 mg/kg was also effective in those individuals taking HU who had still experienced 2-10 SCPCs in the previous year, indicating that P-selectin inhibition provided additional beneficial treatment effect compared with HU alone. Download : Download high-res image (213KB) Download : Download full-size image Disclosures Kanter: Sancillo: Research Funding; Apopharma: Research Funding; MUSC: Other: The site PI for sponsored research conducted at MUSC who receives funds from: Novartis, bluebird bio, GBT, Sancillo, Apopharma, Pfizer; GBT: Research Funding; Pfizer: Research Funding; American Society of Hematology (Sickle Cell Disease Guideline Panel): Membership on an entity's Board of Directors or advisory committees; NHLBI (sickle cell disease research advisory committee): Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: 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. Kutlar: Novartis: Research Funding; BlueBird Bio: Other: Member of Data Monitoring Committee; Sancilio & Co (OMEG-411-02): Other: Chair of Data and Safety Monitoring Board; Reprixys Pharmaceuticals Corporation (formerly known as Selexys Pharmaceuticals Corporation, which is not affiliated with Selexis S.A.): Research Funding. Liles: Pfizer: Research Funding. Bruederle: Novartis: Employment. Shi: Novartis: Employment. Zhu: Novartis: Employment. Ataga: Reprixys Pharmaceuticals Corporation (formerly known as Selexys Pharmaceuticals Corporation, which is not affiliated with Selexis S.A.): Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Research Funding; Novartis: Honoraria; Global Blood Therapeutics: Honoraria; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Exploring Attitudes, Beliefs and Behavior Towards Hormonal Birth Control Among Female Patients with Sickle Cell Disease through Semi-Structured Interviews

▪Background: Sickle cell disease (SCD) is an inherited, autosomal recessive disorder and one way to decrease the risk of transmission of the disease is through informed reproductive choices. The U.S. Medial Eligibility Criteria for Contraceptive Use advises that the benefits of using hormonal contraceptives usually outweigh the risks for women with SCD. Recommendations for contraceptive use for individuals with sickle cell disease do not discourage the use of any specific contraceptives and identify sickle cell disease as a condition that exposes the woman to increased risk as a result of unintended pregnancy. Research indicates that women with SCD use hormonal contraceptives at lower rates than women without SCD.Objective: We sought to understand women with SCD knowledge, attitudes, and practices around hormonal contraceptives.Methods: African American females 18 and older with SCD were recruited from a sickle cell clinic in Atlanta, Georgia. We administered semi-structured interviews to examine the intersection of sickle cell and reproductive health. These semi-structured interviews explored participants' knowledge and attitudes towards hormonal contraceptives, as well as their personal experiences using hormonal contraceptives.Results: Seventeen women were interviewed on this topic. All but two of the participants indicated they had previously used hormonal contraceptives, but most of the women were not currently using hormonal birth control. Some of the participants had positive thoughts towards hormonal birth control because it prevents pregnancy.Birth control period. I am all for it. I feel like that is a good prevention of having unplanned pregnancies and whatever.Women cited positive experiences with hormonal birth control because it helped with heavy menstrual bleeding and decreased the number of sickle cell pain crises they experienced.I had depo before. It just made me gain weight and my cycles were off balance but it kind of helped with the Sickle Cell crisis a little bit.I would have pain crisis every time I had a menstrual cycle so my doctor told me to go to a gynecologist to get onto a birth control so that kind of decreased the amount of crisis that I was getting.Some of the participants had negative perceptions of hormonal birth control. Some were wary of it altogether. Most of them cited the side effects associated with hormonal birth control as the main reason they did not use them.I don't think any women should be on them just because of all the stuff in it. Some stuff they do not tell you what is in it and the weight gain and all the side effects I don't like them.That's why I don't like them because of the symptoms that I had. I wason Depo and I bleed for two months straight. And then I tried another one.Some green pill I don't know. I tried the implant. Like I said all the side effectsI didn't like them. I didn't like when I had side effects with it.Participants had specific concerns about the side effects related to menstrual bleeding and the intersection between contraceptive and sickle cell.I know they can just regulate your menstrual cycle. I kind of feel like that's unnatural. I think God put that in place for a reason and it needs to clean your body out. I just kind of think that part of it is unnatural and it shouldn't happen.I actually had to get one of them took out. The Nexplanon it actually caused a blood clot which is dangerous for a Sickle Cell patient.Right now I have an IUD and at first it was giving me back problems but I think it was just associated with Sickle Cell. So I think maybe it can trigger a Sickle Cell crisis sometimes.Conclusion: Our study findings indicate that women with SCD have low utilization of hormonal birth control with concerns for side effects caused by, and a general distrust of, hormonal contraception. However, some women also acknowledge that hormonal contraception can help prevent unplanned pregnancy, which not only may lead to unintended transmission of SCD, but also increased health risks to the woman. Providers caring for women with SCD may be able to better support them by adopting a patient-centered approach to contraceptive counseling. Seeking to clarify women's reproductive goals, contraceptive priorities and concerns, as well as correcting misinformation and reassuring women about hormonal contraceptive safety for women with SCD may be beneficial. DisclosuresNo relevant conflicts of interest to declare.

Compliance with Expert Recommendations of Sickle Cell Pain Management—a Single Institution Review

Introduction:Sickle cell disease in a lifelong disorder associates with the occurrence of recurrent painful vasoocclusive crisis that often result in frequent emergency room trips and inpatient hospital stays. There are several goals in the management of sickle cell disease including early resolution of painful crisis and reduction of end stage events such as pulmonary hypertension and stroke. Unfortunately, the painful crisis leads to frequent ER visits and sometimes results in lengthy hospital stays. In 2014, The US Department of Health and Human Services came out with an expert report panel dictating recommendations on care for patient with sickle cell disease recommending pain medicine in the emergency room within one hour of triage and use of personal controlled analgesia (PCA) pumps. We opted to look at patient records within Orlando Health, a center with a large sickle cell patient population, to determine if we are following these recommendations.Methods: We reviewed emergency room and inpatient records of 158 patients. We documented if pain medications were started within two hours of arrival to the emergency room (we allowed additional time to account for registration and triage) and we reviewed inpatient records for PCA use. We also looked for trends in PCA use in terms of complexity of hospital stays and length of stay.Results:For sickle cell patients coming into the emergency room, 107/158 (68%) were given pain medication within 2 hours of registration.Of patients admitted to the hospital, only 10/158 (6%) were given a PCA pump. The patients given a PCA pump had an average length of stay of 16 days compared to the general population of 6.1 days. PCA use increased during lengthy hospitalizations rather than being started immediately.The patients who were given a PCA pump were assigned an ER acuity score of 3 compared to the general population of 2.1.Discussion:In caring for patients with sickle cell disease, we often aim to provide quick and effective management of pain crisis. In terms of emergency room management, triage to pain medication time is ideally within one hour. By looking at an extended window to account for registration time, we were able to provide pain medication on time 68% of the time. Per pharmacy staff, the pain medications are kept in the emergency room pharmacy system and should be immediately available upon request. Emergency room physicians identify overcrowding of the ER and the prospect of patient addiction as potential barriers to more immediate access. This thought process can lead to unnecessary suffering from patients.Inpatient PCA use was very infrequently started. Currently the hospitalist service is starting most of the inpatient pain medication. When asked about PCA use, the hospitalist physicians mostly stated that their experience hasn't shown a trend toward shorter length of stay. Additionally, patients frequently state that they prefer push medication to PCA use. Data does exist that the opposite is true, PCA use is associated with shorter length of stay. Education on this data and encouragement of PCA use with patients should be encouraged per expert recommendations. It does appear that PCA use is reserved for patients who are deemed “sicker” or have longer length of stay.We believe these trends are reflective of other institutions and broad education on best management of sickle cell pain crisis may be required. DisclosuresLandau:celgene: Speakers Bureau; sanofi: Speakers Bureau; alexion: Speakers Bureau; novartis: Speakers Bureau; BMS: Speakers Bureau.

Impact of Early Analgesia on Hospitalization for Sickle Cell Pain Crisis

National Institutes of Health guidelines for management of sickle cell acute pain suggests the use of an individualized prescribing protocol to improve outcomes for patients suffering from acute pain. The evidence that individualized pain plans improve clinical outcomes is limited and the recommendation is based on consensus opinion. Prior to implementing individualized inpatient SCD pain plans, we sought to evaluate the time required to achieve maximum opioid dose without individualized prescribing protocols and its negative impact on length of stay.Methods: We conducted an 18-month retrospective cohort study of all SCD pediatric patients admitted from the Emergency Department (ED) for SCD pain. We recorded the ED admission time, order entry time for the maximum opioid dose (mg) during the hospitalization, time that maximum opioid dose was delivered, and time of discharge orders. Maximum opioid dose was defined as total hourly cumulative dose received in oral morphine equivalents. The primary endpoint was time (hours) required to achieve maximum opioid dosage. Secondary endpoints included: total inpatient hours, hours until discharge after a maximum opioid dose had been reached, and the impact of current SCD modifying therapy (hydroxyurea, transfusion, both, or none). Since we plan to first pilot individualized pain plans in patients with recurrent pain events, we a priori defined patients with repeated pain events as those with ≥3 pain admissions during an 18-month period. A priori we dichotomized achievement of maximum opioid dose as “early” (maximum opioid dose ordered within 24 hours from admission) or “late” (ordered >24 hours from admission). Each pain admission was considered an independent event. We performed descriptive statistics, t-test or Wilcoxon for continuous variables, and Fisher's exact test or Chi-squared test for categorical variables, using JMP Pro 12 (Cary, NC).Results: We identified 179 pain admission events among 92 participants over 18 months (range: 1 to 9 events/patient). Data revealed 50% (n=90) admission events occurred in females. The mean age for these admission events was 13.5 years (range: 0.5-19). Genotypes included: HbSS or HbSB0 thalassemia (n=68 (74%)), HbSC (n=21 (23%)), HbSB+ thalassemia (n=3 (3%)). SCD modifying therapy categories included: 97 (54%) participants prescribed hydroxyurea (HU), 23 (13%) receiving transfusion therapy, 11 (6%) receiving transfusion and prescribed HU, and 48 (27%) no SCD therapy. The mean time elapsed until the order for the maximum total daily opioid dose was entered was 24 (SD 42) hours and the mean time until the maximum opioid dose was delivered was 37.3 (SD 48.9) hours. The mean time to maximum opioid order was similar among SCD modifying therapy categories (p=0.3). The mean total hospitalization time was 101 hours (range: 15-455 hours). There was no statistical difference in mean total hospitalization time based on current SCD modifying therapy (p=0.4).We identified 91 admission events among 19 participants that required repeat pain admissions. Participants with repeat pain admission events required more time to achieve a maximum opioid dose than those with two or less pain admissions (31.1 vs 17.5 hours, p=0.03) despite having non-significant differences in time to discharge after the maximum opioid dose was ordered (82.5 vs 70.0 hours, p=0.2). Among repeat admission participants, 60 events (66%) were categorized as “early” achievement of a maximum opioid dose and 31 (34%) were categorized as “late.” Participants with “early” maximum opioid orders had significantly shorter length of total hospital stay (early: 78±54 vs late: 183±96 hours, p<0.0001) as well as shorter time to discharge after that maximum order was placed (early: 71±52 vs late: 105±69 hours, p=0.01). Current SCD therapies did not have an impact on time to maximum opioid order (p=0.4) or total hospital stay (p=0.2).Conclusion: It is important to quickly achieve appropriate analgesia for pediatric SCD patients suffering with pain. Participants with frequent pain admissions that achieved earlier analgesia, as determined by maximum opioid dose within 24 hours, required shorter hospitalizations than patients that required longer titration to maximum opioid dose. Individualized pain plans should be prospectively evaluated to determine their impact on early achievement of analgesia and decreasing hospitalization length of stay. DisclosuresLebensburger:ASH: Research Funding; NHLBI: Research Funding.

A Comparison of Two Regimens for Managing Sickle Cell Pain and Reducing Readmissions

This was a multicenter retrospective analysis comparing intravenous push (IVP) analgesia versus patient-controlled analgesia (PCA) in patients admitted for sickle cell pain crisis. The primary objective was to compare the analgesic management, measured in total daily morphine milligram equivalents (MME). Secondary objectives included length of hospitalization, 30-day hospital readmissions and pain scores. Of the 98 patients identified between August 2017 and August 2018, 68 patients were included in this study. There were 51% (n = 35) in the IVP group and 49% (n = 33) in the PCA group. The majority of patients were on 90 or more daily MME prior to admission. The average total daily MME was significantly higher in patients on PCA compared to IVP on the first three days of hospitalization (289 vs 146, p < 0.01). Length of hospitalization was not different between patients on IVP and PCA (7.14 vs. 6.39 days, p = 0.53). There was no difference in 30-day readmissions, average pain scores on days 1–3 of hospitalization and adverse side effects between the groups. This study showed patients on IVP had significantly lower total daily MME requirements compared to PCA within the first three calendar days of admission.

Hyperhemolysis Syndrome in a Patient with Sickle Cell Disease: A Case Report.

IntroductionHyperhemolysis syndrome (HHS) is a rare complication of repeat blood transfusions in sickle cell disease (SCD). This can occur acutely or have a delayed presentation and often goes unrecognized in the emergency department (ED) due to its rapid progression and similarity to acute chest syndrome and other common complications of SCD.Case ReportWe present a case of a 20-year-old male with SCD who presented to the ED with pain and tenderness in his lower extremities one day after discharge for a crisis. Unbeknownst to the ED team, during his admission he had received a blood transfusion. On presentation he was noted to have hyperkalemia, hyperbilirubinemia, anemia, and uncontrolled pain, and was admitted for sickle cell pain crisis. Over the next 36 hours, his hemoglobin dropped precipitously from 8.9 grams per deciliter (g/dL) to 4.2 g/dL (reference range: 11.5–14.5 g/dL), reticulocyte count from 11.7 % to 3.8% (0.4–2.2%), and platelets from 318,000 per cubic centimeter (K/cm3) to 65 K/cm3 (140–350 K/cm3). He also developed a fever, hypoxia, transaminitis, a deteriorating mental status, and severe lactic acidosis. Hematology was consulted and he was treated with methylprednisolone, intravenous immunoglobulin, two units of antigen-matched red blood cells, fresh frozen plasma, and cryoprecipitate. He was transferred to an outside hospital for exchange transfusion and remained hospitalized for 26 days with acute liver failure, bone marrow necrosis, and a fever of unknown origin.ConclusionBecause of the untoward outcomes associated with delay in HHS diagnosis and the need for early initiation of steroids, it is important for emergency providers to screen patients with hemoglobinopathies for recent transfusion at ED presentation. Asking the simple question about when a patient’s last transfusion occurred can lead an emergency physician to include HHS in the differential and work-up of patients with sickle cell disease complications.

Troponin Elevation in Sickle Cell Disease

Objective: Sickle cell disease is associated with cardiovascular abnormalities. Troponin is not typically measured in this population, and thus the significance of abnormal levels of troponin is unknown. We wanted to evaluate the use of troponin and factors that predispose troponin elevation in patients admitted with sickle cell pain crisis (SCPC). Methods: We reviewed data of consecutive patients admitted to a tertiary care hospital between 2006 and 2011 with a diagnosis of SCPC. Subjects with elevated troponin (ET) (troponin I >0.04 ng/mL) were compared with those with normal troponin (NT) for demographics, risk factors, presence of echocardiography-derived tricuspid regurgitant jet velocity (TRV) ≥3 m/s suggesting pulmonary hypertension, and laboratory tests. The Mann-Whitney U test was used to compare groups. Results: Two hundred eighty-three of 724 patients admitted with SCPC had chest pain. Troponin I was measured in 63 patients: 51 had NT and 12 had ET ranging from 0.06 to 3.42 ng/ml. ET was associated lower hemoglobin (p = 0.02), lower hematocrit (p = 0.02), lower platelet number (p < 0.001), higher LDH (p = 0.012), higher AST levels (p = 0.004), higher bilirubin levels (p = 0.006), and TRV ≥3 m/s (p = 0.028). Conclusions: Troponin was measured in <10% of patients with SCPC, and 1 out of 5 of them had ET. Troponin elevation was not associated with traditional cardiovascular risk factors but was associated with lower hematocrit, elevated LDH, bilirubin levels, and TRV ≥3 m/s.

Thrombolysis After Emergency Cesarean Section in Sickle Cell Disease

Pulmonary embolism (PE) is a rare complication during pregnancy. However, it is still the leading cause of morbidity and mortality. The risk to develop a PE is even higher in patients suffering from an inherited blood disorder like sickle cell disease (SCD). We report on the management of a 28-year-old woman with SCD who was admitted to the hospital with painful sickle cell crisis and developed a massive PE followed by cardiac arrest. The patient could be revived and underwent thrombolysis successfully with recombinant tissue plasminogen activator (r-tPA) 22 h after emergency cesarean section without complications related to thrombolysis. However, she developed an acute kidney injury and transient liver dysfunction which both improved gradually during her course. Finally, she was extubated on the 16th postoperative day and transferred to the obstetric ward on the 21st postoperative day. The patient recovered completely and was discharged home without neurological deficit. J Clin Gynecol Obstet. 2020;9(4):124-128 doi: https://doi.org/10.14740/jcgo668

Outcomes of Red Cell Exchange in Pregnant Patients with Sickle Cell Disease: A Case Series

Background: Pregnant patients with sickle cell disease (SCD) have higher morbidity compared to patients without SCD. SCD during pregnancy can increase the risk of fetal and obstetrical complications including preterm birth, preeclampsia, and others. Moreover, during pregnancy SCD can become more severe resulting in more sickle cell vasoocclusive crisis. Prophylactic transfusion during pregnancy has been used in practice to reduce sickle cell pain crisis since hydroxyurea is contraindicated during pregnancy. However, using prophylactic red blood cell exchange (RBCX) has been a controversial topic. In this study, we aim to evaluate the outcomes of red blood cell exchange in pregnant patients with SCD Methods: This is a retrospective study. We evaluated the charts of three pregnant patients who were enrolled in the chronic RBCX program at the University of Nebraska Medical Center at the time of their pregnancy. Data was collected to assess the sickle cell disease related complications during pregnancy, outcomes of pregnancy, and safety of the red blood cell exchange. Results: A total of 19 exchange procedures were performed for three pregnant patients while being enrolled in the chronic red blood cell exchange program. Patients demographic is summarized in table 1. The indication for enrollment in the red cell exchange program were recurrent vasooclussive crisis in patient 1 and 3, avascular necrosis in patient 2. The pregnancies were uncomplicated except for preeclampsia in the third patient resulting on early delivery. Overall, the three patients had less frequent visits to the emergency room for sickle cell related complications after starting apheresis and during pregnancy (Figure 1). We believe that the modest improvement that was noticed for the third patient was due to late enrollment in the exchange transfusion program and her older age compared to the two other patients Conclusion: Our study shows that red blood cell exchange for SCD patients during pregnancy can be safe, feasible, and can reduce the visits to the emergency room due to SCD related complication. Further larger studies are warranted to confirm this. Disclosures Gundabolu: BioMarin:Consultancy;Bristol Myers Squibb pharmaceuticals:Consultancy.

A Multiyear Cross-sectional Study of Guideline Adherence for the Timeliness of Opioid Administration in Children With Sickle Cell Pain Crisis

The National Heart, Lung, and Blood Institute evidence-based guidelines for timeliness of opioid administration for sickle cell disease (SCD) pain crises recommend an initial opioid within 1 hour of arrival, with subsequent dosing every 30 minutes until pain is controlled. No multisite studies have evaluated guideline adherence, to our knowledge. Our objective was to determine guideline adherence across a multicenter network. We conducted a multiyear cross-sectional analysis of children with SCD who presented between January 1, 2016, and December 31, 2018, to 7 emergency departments (EDs) within the Pediatric Emergency Care Applied Research Network. Visits for uncomplicated pain crisis were included, defined with an International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 code for SCD crisis and receipt of an opioid, excluding visits with other SCD complications or temperature exceeding 38.5°C (101.3°F). Times were extracted from the electronic record. Guideline adherence was assessed across sites and calendar years. A total of 4,578 visits were included. The median time to first opioid receipt was 62 minutes (interquartile range 42 to 93 minutes); between the first and second opioid receipt, 60 minutes (interquartile range 39 to 93 minutes). Overall, 48% of visits (95% confidence interval 47% to 50%) were guideline adherent for first opioid. Of 3,538 visits with a second opioid, 15% (95% confidence interval 14% to 16%) were guideline adherent. Site variation in adherence existed for time to first opioid (range 22% to 70%) and time between first and second opioid (range 2% to 36%; both P<.001). There was no change in timeliness to first dose or time between doses across years (P>.05 for both). Guideline adherence for timeliness of SCD treatment is poor, with half of visits adherent for time to first opioid and one seventh adherent for second dose. Dissemination and implementation research/quality improvement efforts are critical to improve care across EDs.

Trigger Unhappy? New Evidence Supports Mental Stress Can Trigger Microvascular Occlusion and Potentially Lead to Sickle Cell Pain Crisis

Trigger Unhappy? New Evidence Supports Mental Stress Can Trigger Microvascular Occlusion and Potentially Lead to Sickle Cell Pain Crisis

Perceived stigma among adolescents with sickle cell anemia in a tertiary health facility

Background Adolescents with sickle cell anemia (SCA) are challenged by a myriad of complex psychosocial issues, which may be triggered or exacerbated by stigmatization. The magnitude of childhood stigma is scarcely being assessed, as more focus is often given to the physical symptoms and signs of SCA. This study sought to assess the prevalence of perceived stigma and its associated factors among adolescents with SCA in steady state. Patients and methods Using a cross-sectional design, 200 adolescents with SCA (patients) were recruited consecutively from the Paediatric Haematology Clinic. Controls matched for age, sex, and socioeconomic class, with hemoglobin genotype AA or AS, were recruited from the Children Outpatient Clinic. A self-administered questionnaire was used to obtain the clinicodemographic data. A validated perceived stigma scale was used in this study. Bivariate and multivariate analyses were performed at 0.05 significant level. Results There were 97 (48.5%) males and 103 (51.5%) females in each group. Perceived stigma was present in 159 (79.5%) patients and 16 (8.0%) controls (P=0.001). Perceived stigma was significantly higher among patients who were in their early and mid-adolescence, those who had sickle cell pain crises frequency of greater than thrice a year, and those with poor self-perception. Patients in early and mid-adolescence were about three times more likely to experience perceived stigma than those in late adolescence (odds ratio=2.9; 95% confidence interval=1.1–7.7; P=0.031). Conclusion Stigma is a major problem among adolescents with SCA. Regular screening for stigma is recommended for patients with SCA, especially those in early and mid-adolescence.

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.

Characteristics of Marijuana Usage in Sickle Cell Patients: A Nationwide Analysis

Introduction Sickle cell disease (SCD) associated pain is a significant health care issue in the United States which prompts physicians to prescribe opioids to help treat and prevent the recurrent acute painful episodes. Despite nationwide efforts to reduce narcotic pain medication usage, opioids still remain as the mainstay of pain management in SCD. Many SCD patients are using marijuana to help with their pain, anxiety, appetite, mood and sleep as per recent studies. Cannabinoids in marijuana interact with the body's endocannabinoid system which has receptors in almost every major bodily system. The effect of cannabinoids on these receptors reduces the signaling of inflammatory responses and also reduce cytokine production. Very few states have approved SCD as a qualifying condition for medical marijuana. But we are still unsure about the medical benefits of marijuana in SCD patients as there are very limited studies done so far. In our study, we sought to examine the characteristics and complications of marijuana usage in sickle cell patients. Methods The National Inpatient Sample database for the year 2016 was used to identify admissions with a primary diagnosis of SCD and we grouped patients into those who have a diagnosis of cannabis related disorders (CRD) and those who do not have the diagnosis. ICD- 10 codes are used for identifying the SCD patients and also for CRD. Statistical analysis was performed using STATA and univariate and multivariate analysis were performed. The outcomes that are studied included mortality, length and cost of stay, hospital regions and the association of marijuana use with anxiety, mood disorders. We also studied the association of marijuana with the complications of SCD such as sickle cell pain crisis, vaso occlusive crisis, acute chest syndrome, splenic sequestration, avascular necrosis. Results A total of 37,307 admissions with a principal diagnosis of SCD were identified, out of which 4.09% (N= 1526) had cannabis use disorders. The median age of patients with CRD was found to be 31.21 ± 0.3 when compared to 30.67 ± 0.09 in patients without CRD. Even though SCD admissions were more commonly seen in females when compared to males (61.78% vs 38.22%), cannabis use was seen more associated with males (57.97% vs 42.03%). The in-hospital mortality of SCD was less (0.56%) as compared to the mortality rates of other hematological malignancies. The association of cannabis use with in-hospital mortality was found to be not statistically significant. Also, the median length of stay was less in patients with CRD when compared to patients without CRD (4.88 ± 0.2 vs 5.11 ± 0.03) and also likewise cost of stay. Based on the hospital regions in the US, Cannabis use in SCD was seen more prevalent in South region (44%), then Midwest or north-central (26%), northeast (19%), west (10%) and the result was statistically significant (p= 0.003). The association of cannabis use was not found to be statistically significant with acute chest syndrome and splenic sequestration. Cannabis use was, however, found to be associated with the vaso occlusive crisis and avascular necrosis (OR=1.02, p=0.003 and OR= 1.14, 0.022 respectively) even though we cannot say that cannabis use could be a risk factor as there are other confounding factors like coagulopathy, chronic debilitating conditions. Interestingly, SCD patients with CRD have more risk of developing anxiety (OR= 2.32, p=0.000) and also mood disorders (OR= 2.5, p= 0.001) when compared to SCD patients without CRD. The difference persisted after adjusting for age, gender, race, co-morbidities. Conclusion Marijuana use is more seen in the southern and north-central regions in patients with SCD. Marijuana use was not found to be associated with in-hospital mortality in sickle cell patients. SCD patients are using marijuana mainly for alleviating their pain and sometimes for its euphoria effect. Our study showed that it can cause anxiety and mood disorders. The main limitation of our study was the moderate sample size for SCD patients with CRD. The impact and interaction between CRD and SCD complications need to be evaluated separately in a larger study to get accurate values. Large randomized control trials have to be done to assess if SCD qualifies for prescription of medical marijuana as it possesses benefits as well as risks. Disclosures No relevant conflicts of interest to declare.

Potentially Modifiable Risk Factors for 30‐Day Readmission in Adults with Sickle Cell Disease: A National Database Study

Introduction The overall impact of morbidity related to sickle cell disease (SCD) is enormous due to decreased quality of life, high health care utilization and immense financial strain on the patients and health care system. Patients with SCD have also been found have high hospital readmission rates compared to other medical conditions, further leading to increased health care burden. The objective of this study was to explore the common reasons, healthcare utilization and identify modifiable factors associated with 30-day readmission in patients with SCD using the most recently available national data in the United States. Methods Cohort selection. 2016 Nationwide Readmission Database (NRD) from the Healthcare Cost and Utilization Project (HCUP) by the Agency for Healthcare Research and Quality (AHRQ) was queried for analysis. NRD captures discharge data from 22 states, representing about 50% of all hospitalizations in the United States. National estimates can be produced by using sampling weights provided by the NRD. Patients with SCD were identified by using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code D57. Patients younger than 18 years were excluded. Readmission was defined as any admission within 30 days of index hospitalization discharge. Statistical Analysis. Sampling weights were used throughout all calculations, facilitating appropriate national projections. Percentages in all figures reflect national estimates. Chi-square test and Student's t-test were used for univariate analysis. Multivariable logistic regression analysis was done to determine independent predictors of 30-day readmission in patients with SCD. Data analyses was performed using SAS v9.4 (SAS Institute, Cary, NC). Results In a total of 83,692 hospitalizations for SCD in 2016, 15,880 (18.9%) had at least one 30-day readmission and 40% of the readmissions occurred within the first two weeks of discharge. The most common reason for 30-day readmission was due to complications of SCD (29.8%) with sickle-cell pain crisis (18.4%) being the most frequent one. The other common causes for readmission were sepsis (10.3%), cardiac related (9.7%), respiratory failure (6.2%), renal failure (4.3%) and mood related (4.04%). Female sex (P&lt;0.001), younger age (p&lt;0.01) and patients with public insurance (P &lt;.001) were more likely to be readmitted. Multivariable logistic regression analysis showed age 31-45 years (OR 1.28, 95% CI 1.16 - 1.40, P&lt;0.01), alcohol abuse (OR 1.39, 95% CI 1.17 - 1.66, P&lt;0.001), opioid abuse (OR 2.66, 95% CI 2.34 - 3.02, P&lt;0.0001), depression (OR: 1.59, 95% CI 1.45 - 1.73, P&lt;0.01), substance abuse (OR: 1.35, 95% CI 1.21 -1.50, P&lt;0.001), tobacco use (OR: 1.35, 95% CI 1.24 - 1.46, P&lt;0.01), heart failure (OR: 1.81, 95% CI 1.66 - 1.97, P&lt;0.002), COPD (OR: 1.74, 95% CI 1.55 - 1.96, P&lt;0.03) were significantly associated with 30-day readmission while adjusting other co-morbidities. The mean cost of readmission was an additional $39,259 (±182). Conclusion This study showed that the 30-day readmission rate in patients with SCD in 2016 has decreased to less than 20% compared to previously published rates (31.9%, Elixhauser A, 2013). While this decrease in readmission rate is encouraging, further studies are needed to investigate the reasons for this trend. Several modifiable risk factors were identified in this study such as alcohol, tobacco, opioid, substance abuse and depression which can be addressed to potentially bring down the readmission rate further and improve patient care. Disclosures No relevant conflicts of interest to declare.

3177 Splenomegaly in an Adult Female With Sickle Cell Disease

INTRODUCTION: A mutation in the beta globin chain of hemoglobin results in Sickle type of Red blood cells. To remove the sickle shaped red blood cells, the spleen becomes hyperactive and enlarged. These red cells have more affinity to the vascular endothelial membrane resulting in Vaso-occlusive phenomenon. Repeated episodes of this cause thrombosis, infarction leading to fibrosis and Autosplenectomy. This is generally complete by the age of 5 and for more than 80% in their first decade. Existence of spleen in adolescents and adults with sickle cell disease in uncommon. Here we present such a case. CASE DESCRIPTION/METHODS: A 22-year-old female with known history of homozygous sickle cell disease presents with abdominal pain. She started to have generalized body pains, later localized to all quadrants of the abdomen. She described it as achy type constant pain associated with nausea. She denies any emesis, changes with bowel or bladder habits and association with food intake. CT imaging done revealed an enlarged spleen with scattered densities and a 2 cm splenule in the inferior aspect. The enlarged spleen 14 × 5 × 15 cms was present in prior ultrasound imaging study done 4 years ago. Further laboratory work including complete blood counts with differential, reticulocyte count &amp; index were consistent with sickle cell pain crisis. DISCUSSION: Although the presence of echogenic lesions increases the risk of sequestration crisis, increased Hemoglobin F levels and alpha thalassemia may cause splenomegaly, but the patient did not have either. Hemoglobin Electrophoresis showed Hb F 1% and Hb S of 70%. Some studies conclude splenic enlargement in adulthood may imply less severe form of the disease. With no other possible cause identified, this adult female with Sickle cell HbSS disease has Splenomegaly.

226 Ketamine Use for Acute Painful Crisis of Sickle Cell Disease: A Randomized Controlled Trial

Because treatment options are limited, management of acute painful crises in sickle cell disease (SCD) patients is challenging. Pain control with opioids is the mainstay of treatment but is associated with adverse effects and carries a risk of dependency. The objective of this study is to determine if ketamine therapy is superior to opioid therapy alone in the management of acute sickle cell pain crisis. This is a prospective parallel groups randomized controlled trial in which patients were randomized in a 1:1 ratio to receive either a single dose low-dose ketamine (0.3 mg/kg in 0.9% sodium chloride, 100 ml bag) or a single dose morphine (0.1 mg/kg in 0.9% sodium chloride, 100 ml bag) infused over 30 minutes including subsequent pain management with opioids at the treating physician’s discretion. The primary outcome was the changes in the numerical pain rating score (NPRS) over time. Secondary outcomes included the cumulative dose of opioids, emergency department (ED) length of stay, hospital admission rate, and drug-related side effects. We conducted the analysis using the intention-to-treat principle and generalized estimation equations to model the average difference between groups across all time points (30, 60, 90, 120 minutes). Of the 278 patients randomized, 140 patients were allocated to ketamine arm and 138 patients to morphine. Ketamine use compared to morphine was associated with similar reduction in NPRS 5.6 versus 5.7 (mean difference 0.13; 95% confidence interval (CI) -0.34 to 0.60). The use of rescue opioid analgesia (MD 0.74 mg morphine equivalent; 95% CI -0.36 to 1.84), ED stay (MD -3.99 min; 95% CI -35.85 to 27.85), hospital admission (OR 0.71; 95% CI 0.44 to 1.39), and drug-related side effects were similar between groups. Sensitivity per-protocol analyses yielded similar results to the main analyses. The use of ketamine in patients with acute sickle cell pain crisis was not superior to morphine in reducing NPRS over the first 2 hours of treatment, nor in reducing rescue opioids, ED length of stay, or hospitalization with similar drug-related side effects.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Ischemic colitis in a known sickle cell disease patient

Patients affected with sickle cell disease (SCD) suffer from recurrent vascular occlusions that lead to ischemia and distal tissue infarction in multiple organs. These vascular occlusions manifest as sickle cell pain crises. Abdominal pain is common in sickle cell pain crises. It is attributed to vasoocclusion or infarction in the mesenteric vasculature. Progression to significant ischemic damage of the intestine is rare in sickle cell disease. The objective was to show the rare case of ischemic colitis in SCD patient. The patient’s images (plain abdominal x rays and barium enema images) and case file were reviewed and summarized. The subject matter of ischemic colitis in a known SCD was reviewed in the literature. The index case was discussed and compared with literature. We report an 18-year-old known SCD patient diagnosed since childhood but not regular on medication and follow up. The patient presented to SCD clinic of Aminu Kano Teaching Hospital (AKTH), Kano with 2-year history of recurrent blood stained and watery stool associated with abdominal pain and low-grade fever. There was history of easy fatigability and multiple blood transfusions in the past. Other systemic reviews were unremarkable. This man is the only sickle cell anemic child among 9 other siblings of the family, and on presentation, a second-year student of a junior secondary school. Examination revealed a stunted young man, mild pale with a tinge of jaundice. Abdominal examination revealed hepatomegaly 4 cm below the costal margin. The spleen was not enlarged. Other systemic reviews were unremarkable. Latest hemoglobin was 5.7 g/dL. Renal and the liver function tests were normal. Stool microscopy did not isolate ova, cyst or protozoa. Barium enema was then requested and showed loss of haustration and cobblestone appearance involving the entire colon. Fine mucosal granulations were also noted in the rectum. Diagnosis of colitis most probably ischemic was made. The patient was commenced on analgesics and antibiotics including azithromycin and metronidazole and made significant improvement. Ischemic colitis in SCD may still be encountered in practice despite its rarity.

Applying Neural Network-Based Approach to Sickle Cell Disease-Related Pain Classification

Sickle Cell Disease (SCD), an inherited Red Blood Cell (RBC) disorder, is characterized by anaemia, end-organ damage, unpredictable episodes of pain and early mortality. SCD affects 25% of people living in Central and West Africa causing life threatening “silent” strokes and lifelong damage. Nigeria accounts for 50% of SCD births worldwide (estimated 150,000 of 300,000 babies born with Symptomatic Sickle Cell Anaemia (SSCA) yearly, an annual infant death of 100,000 (8% of her infant mortality)) and about 2.3% of her population suffers from SCD with 40 million (25%) being healthy carriers. The number of such babies born with SSCA yearly has been estimated as 400,000 by year 2050. Healthcare resources for SCD are inadequate and the numbers of SCD are increasing daily, thereby demanding more sufficient resources. Intermittent and recurrent acute pain episodes are associated with SCD as a result of vaso�occlusion. Pain management at the Emergency Department for vaso�occulsive crisis for patients with SCD has been obnoxious. Biopsychosocial assessment and multidisciplinary pain management may be required when treating patients with frequent, painful sickle cell crises. Early and aggressive SCD-related pain management becomes a priority to improve quality of life and prevent worsening morbidities. Computational Intelligence-based framework in promoting higher-quality care and consequent increased life-expectancy in SCD patients is expedient. Monte Carlo Simulation Technique of Random Number Generation was used to generate 515 datasets for enhanced fifteen attributes of SCD. The datasets’ features of SCD were used to train the neural network according to the pain encountered in identifying and treating the patient as fast as possible. This paper provides back-propagation algorithm of Artificial Neural Network in optimizing SCD-related pain classification and treatment processes, to complementa multidisciplinary care team intervention thereby increasing the quality of life

S853 SUCCESSOR: A MULTICENTER RETROSPECTIVE NONINTERVENTIONAL FOLLOW‐UP STUDY IN PATIENTS WITH SICKLE CELL PAIN CRISES WHO PREVIOUSLY PARTICIPATED IN THE SUSTAIN TRIAL IN THE UNITED STATES

Background:SUCCESSOR (SUSTAIN Chart‐review of Crizanlizumab to Evaluate Sickle‐cell Study One‐year Retrospective) reviewed medical records of patients who completed the SUSTAIN study at US sites to assess subsequent cases of significant pain crisis events and generate real‐world data on treatment patterns and health care resource utilization upon completion of crizanlizumab treatment. SUSTAIN was a phase 2, randomized, double‐blind, placebo‐controlled, 52‐week study that compared the effect of crizanlizumab, a P‐selectin inhibitor, versus placebo on the frequency of sickle cell pain crises (SCPCs, or vaso‐occlusive crises [VOCs] leading to a health care visit) in patients with any genotype of sickle cell disease (SCD).Aims:To determine the 52‐week post‐SUSTAIN occurrence of VOCs, time to first VOC, frequency of blood transfusions, and use of opioids and hydroxyurea in patients after withdrawal of treatment with crizanlizumab or placebo.Methods:SUCCESSOR is a multicenter, retrospective cohort study of patients (≥18 years old) who participated in SUSTAIN to evaluate SCD‐related outcomes up to 52 weeks following trial completion. SUCCESSOR included the SUSTAIN per‐protocol population who received at least 12 of the 14 study drug doses, completed a visit at least 14 days after the final dose, and had no major protocol deviations that impacted efficacy assessments. The study period was from September 2015 to March 2017 and patients’ data were obtained from medical records. Crizanlizumab was not administered in the 52 weeks post‐SUSTAIN. An exploratory analysis was conducted to evaluate outcomes in the retrospective SUCCESSOR study using a subset of SUSTAIN patients. Patient consent was obtained prior to data collection if required by local and/or central research ethics review.Results:In SUCCESSOR, data for 48 patients were analyzed (15, 18, and 15 patients who were previously randomized in SUSTAIN to receive crizanlizumab 5 mg/kg, crizanlizumab 2.5 mg/kg, and placebo, respectively). The median age was 31.5 years (range 19–65 years) and 69% were female. One patient had HbSβ+, 4 had HbSβ0, 10 had HbSC, 1 had HbS‐Lepore disease; all remaining patients had HbSS. In the 52 weeks post‐SUSTAIN, VOCs were reported by 73% of patients who previously received crizanlizumab 5 mg/kg, 83% of patients who previously received crizanlizumab 2.5 mg/kg, and 80% of patients previously treated with placebo. The mean annual rate of VOCs was 2.7, 3.9, and 5.4 in patients previously on crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively. Median time to first VOC post‐SUSTAIN was 6.1, 2.7, and 2.6 months in patients previously on crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively, similar to differences observed for the same patients during SUSTAIN (6.9, 2.2, and 1.4 months for crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively). In SUCCESSOR, all but 1 patient utilized opioids, and 79% did not require blood transfusions. Hydroxyurea was used by 60%, 50%, and 80% of patients previously on crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively. There were no deaths.Summary/Conclusion:In SUCCESSOR across all patient groups, 80% of patients experienced a VOC in the 52 weeks post‐SUSTAIN. This retrospective cohort study indicates that after withdrawal of crizanlizumab, patients previously treated with 5 mg/kg maintained a similar time to first VOC compared with time to first VOC while on treatment in SUSTAIN. Further research is needed to establish whether these findings are due to a prolonged effect of crizanlizumab or to other factors.image