Sickle Cell Disease Presenting Research Articles

Impact of Ketamine in the Management of Painful Sickle Cell Disease Vaso-Occlusive Crisis.

The aim of the study is to determine if ketamine infusions in combination with opioid therapy for the management of sickle cell disease (SCD) presenting with vaso-occlusive crisis (VOC) resulted in a length-of-stay difference compared to when ketamine was not utilized. This single center, retrospective, observational study performed at an academic medical center evaluated 12 adult patients with SCD-VOC who received a ketamine infusion with standard opioid therapy between 2014 and 2017. Patients were excluded if the primary diagnosis was not VOC or they did not survive to discharge. Additionally, safety and oral morphine equivalents at various time points were compared. Patients were used as their own control using the previous SCD-VOC hospitalization to evaluate the relative impact of ketamine. Wilcoxon signed-rank and rank sum were used in statistical analysis. When comparing opioid doses during the ketamine infusion, a P-value <.005 was considered statistically significant to account for multiple comparisons. The median length-of stay when ketamine was employed was similar to the previous admission with only opioid therapy (12 vs 12 days, P = .317). The median opioid dose 24 hours prior to starting ketamine was greater than during the first 24 hours of ketamine use (1278 vs 1020 mg, P = .022) and 24 hours after stopping ketamine (1278 vs 1035 mg, P = .014); however, this was not statistically significant. During 5 ketamine infusions, patients experienced side effects; however, only 1 necessitated transfer to the intensive care unit. Compared to standard opioid therapy, ketamine infusions were generally well tolerated and may be effective at reducing opioid use during SCD-VOC but did not decrease hospital length-of-stay.

Plain film x-rays in the diagnosis of sickle cell limb pain in children

Background and aims: Children with sickle cell disease (SCD) frequently present with limb pain. Differentials include vaso-occlusive episode (VOE) and osteomyelitis (OM). X-rays expose to radiation but rarely aid in diagnosis. We audited the use of x-ray in investigating children with SCD presenting with limb pain to a South London hospital and analysed whether x-rays aid in diagnosis.&#x0D; Methods: Patients aged 0-18 with SCD were identified using the hospital’s SCD database. Admissions from January 2010 to September 2019 in which limb pain was a documented symptom were included.&#x0D; Results: Of 342 patients investigated, there were 188 admissions with limb pain. Diagnoses at discharge were: 174 VOE, 4 OM, and 7 others. 44 (25%) of those with VOE had limb x-rays, compared with 3 (75%) of those with OM. Of those x-rayed, 11 with VOE and all with OM had a subsequent MRI. None of the x-rays assisted in confirming the diagnosis or change management. Of the VOE patients, more of those that were x-rayed had swelling (48% vs 8%, p=&lt;0.0001), and fevers (57% vs 37%, p=0.021), and peak CRP was higher (109 vs 75, p=0.044).&#x0D; Conclusions: X-rays were frequently used to investigate children with SCD. Limb swelling, fevers and higher CRP, features potentially suggestive of OM, were more common in those that were x-rayed. X-rays did not aid in distinguishing VOE and OM or change management.

Investigation of Chest X-Ray Use in the Emergency Department in Pediatric Patients with Sickle Cell Disease Presenting with Fever Compared to Age Matched Controls

Background In sickle cell disease (SCD), acute chest syndrome (ACS) is associated with prolonged hospitalization, increased risk of respiratory failure, future lung disease and 25% mortality in hospitalized patients(Bakshi, &amp; Krishnamurti, 2017; Vinchinsky et al. 1997). Pediatric patients with SCD frequently present to the Pediatric Emergency Department (PED) with complaints of fever, chest pain, and cough, all of which may or may not be related to ACS. It is challenging for PED providers to determine which patients are at highest risk of ACS, so chest X-Rays (CXR) are frequently ordered which increases radiation exposure and healthcare costs. The objective of this study was to identify incidence of CXR performance, as well as ACS diagnosis, in SCD patients presenting to our PED with or without fever. Our goal was to identify significant clinical predictors of ACS in this population in order to implement a diagnostic algorithm for PED providers. Methods This was an IRB-approved retrospective medical record review of subjects diagnosed with SCD with inclusion criteria: ages 2-12 years, who presented to the University of Maryland PED between 2016-2018. We performed bivariate analyses comparing these variables between subjects who were febrile vs. afebrile on presentation to the PED, as well as those who were ultimately diagnosed with ACS compared to those who were not. Analysis of categorical variables was performed using Chi-square or Fischer exact test as appropriate. We performed a multivariable logistic regression model to identify significant predictors of ACS diagnosis. Analyses performed using SAS 9.4. Results We identified 424 SCD subjects who presented to our PED meeting inclusion criteria, with 25% (n=108) presenting with fever. Of these, 69% received a CXR on presentation vs. 42% of afebrile subjects (p=&amp;lt;0.0001). In our febrile group 21% (n=23) patients had more than 2 febrile episodes and 100% received CXRs. There were no significant differences between the febrile and afebrile subjects when it came to sex, asthma diagnosis/comorbidity, hydroxyurea use, folic acid supplementation, or pneumococcal prophylaxis. Overall, 10% of patients presenting to the PED were diagnosed with ACS (n=42), made up of 13% of those presenting with fever vs. 9% of those presenting without fever. Those subjects ultimately diagnosed with ACS were significantly more likely to present with chest pain (p=0.003), tachypnea (p=0.001), and hypoxia (p&amp;lt;0.0001), and were more likely to have a past history of asthma (p=0.0085). Sickle cell variant, home medications, and history of splenectomy were not significantly associated with ACS diagnosis. Upon multivariable modeling, when adjusting for fever and pre-existing asthma diagnosis, the only significant predictors of ACS diagnosis were chest pain and hypoxia. Patients without chest pain had an odds ratio (OR) =0.3 of ACS diagnosis [95% Confidence Interval, CI 0.14-0.67], indicating they had 70% lower odds of ACS compared to patients with chest paint. Patients without hypoxia had OR=0.12 of ACS compared to those with hypoxia [CI 0.06-0.25], indicating an 88% reduced odds of ACS diagnosis. Conversely, those with chest pain had 3.3x the odds of ACS diagnosis [CI 1.5-7.4] and those with hypoxia had 8.4x the odds of ACS diagnosis [CI 4-17.9] compared to those without these symptoms. Conclusion In ACS, current guidelines recommend that patients presenting with fever, hypoxia, tachypnea, tachycardia and abnormal respiratory exam findings should be treated empirically as well as receive a CXR. However radiological signs can be delayed compared to physical signs so a normal CXR does not preclude the diagnosis of ACS if there is clinical suspicion(Howard et al. 2015). Our data demonstrate that clinical findings such as chest pain, tachypnea and hypoxia were most likely to correlate to a diagnosis of ACS. While 69% of our febrile patients received a CXR in the PED, only 13% were ultimately diagnosed with ACS, indicating that more CXRs and radiation exposure occurred in the febrile population than may have been necessary. When adjusting for fever and asthma, the most notable predictors of ACS were hypoxia and chest pain. When present, these findings are significant predictors of ACS; when absent, subjects had significantly decreased odds of ACS. Incorporating the presence or absence of chest pain and hypoxia may help focus the use of CXR on the appropriate patient population. Disclosures No relevant conflicts of interest to declare.

Utility of Procalcitonin in the Early Diagnosis of Patients with Sickle Cell Disease Presenting with Fever

Background: Patients with sickle cell disease (SCD) are at increased risk of developing bacterial infections as a result of functional asplenia. Fever, a common symptom in SCD often occurs with other sickle cell related conditions and viral infections. This poses a diagnostic challenge and early use of empiric antibiotics is recommended while awaiting cultures. The widespread administration of antibiotics to all patients with SCD with fever can result in problems such as antibiotic resistance and increased medical costs. An early and reliable biomarker is therefore needed to help distinguish between bacterial and non-bacterial causes for fever in SCD. Procalcitonin (PCT) has been shown to be elevated in bacterial but not viral infections. In SCD, few studies have looked at the role of PCT in predicting bacterial infections. Unal et al reported vaso-occlusive crisis (VOC) with or without fever did not increase PCT levels in relation to patients with no crisis and no fever. However, Rincón-López et al reported a PCT &amp;lt; 0.6ng/mL had a negative predictive value of 97.2% and potentially could be used to identify bacterial infection early. Methods: We retrospectively studied 122 patients with SCD who presented to the emergency department with fever from 2015-2019. Inclusion criteria were defined as patients with SCD, 17 years and older and PCT measurement on presentation to the emergency department. Exclusion criteria were defined as patients with SCD and fever who had received empiric antibiotics prior to labs being drawn in the emergency department. The cohort was divided into groups of patients with Confirmed Bacterial Infection (CBI, n=18), Suspected Bacterial Infection (SBI, n=6), Viral Infections (n=10) and Vaso-Occlusive Crises (VOC, n=88) only. CBI was defined as a positive bacterial culture (blood, body fluid, urine, respiratory or cerebrospinal fluid) or C.difficile toxin assay. Viral infections were defined as a negative bacterial culture in the presence of a virus found on PCR obtained with nasopharyngeal swab. Characteristics including genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin, hydroxyurea use and length of stay were examined. Data was analyzed between the groups using descriptive statistics and accounting for unequal variances, with p-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The mean age was 34.6 years with predominantly males (64.8%). Almost two-thirds were on hydroxyurea (62.3%). The most common genotype was HbSS (70.5%) followed by HbSC (26.2%) and HbSβ (3.3%). The mean PCT for patients with CBI was 8.99 ng/mL (range, 0.03-78.36) as compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group. The most common organisms detected were E.coli, C.difficile, Pseudomonas, Staphylococcus and Enterobacter. There was a significant difference between median PCT for patients with CBI and those with VOC (p=0.036) and between patients with CBI and viral infections (p= 0.045). Using a PCT of &amp;gt;0.5ng/mL resulted in 81% Sensitivity and 85% Specificity for CBI. Conclusion: In patients with SCD presenting with fever, PCT on presentation was significantly higher in those with CBI compared to VOC only or Viral Infection. Disclosures No relevant conflicts of interest to declare.

Sickle Cell Disease Related Outcomes in Patients Evaluated for COVID-19 Infections in South Carolina

Introduction:The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), first identified in Wuhan, China, was declared a pandemic by WHO in March 2020 due to its high transmission rate. Due to the diffuse vasculo-endothelial damage, individuals with Sickle Cell Disease (SCD) are at risk to develop severe clinical complications, if infected with coronavirus 19 (COVID-19).[1] Given this risk, a systematic evaluation of individuals with SCD presenting with COVID19 infection is paramount to identify the variable clinical manifestations and complications encountered in children and adults with SCD.Methods:A retrospective chart review was conducted from January to June 2020 at the Medical University of South Carolina. We included individuals with sickle cell disease of all genotypes, from 0 to 65 years of age found to be positive for COVID19 by polymerase chain reaction (PCR). Patients' past medical history, clinical presentations, admissions, treatment, complications, and mortality data were reviewed. The data was collected with REDCap@ and descriptive data analysis was conducted per SPSS@.Results:Of the identified 23 patients with SCD who tested positive for COVID during the time specified, 19 (82.6%) had Hgb SS genotype, two had Hgb SC (9%) and two Hgb Sβ+ thalassemia (9%) with similar incidence in both genders (47.8% male and 52.2 % female). All patients were African American. The mean age was 26.13+/-11.53 years. In the last three years they had admissions for pain at a mean of 4.29 +/- 5 and admissions for acute chest syndrome 1+/- 2.2. Six participants (26.1%) had history of mild asthma. Two (8.7%) had pulmonary hypertension. No participants had a history of silent stroke. One participant had history of ischemic stroke, three (13%) had history of pulmonary embolism, and six (26.1%) had deep vein thrombosis (DVT). A variable clinical presentation was noted in our population (Table 1).Of the 23, only nine (39%) required admission of which only one met criteria for intensive care (4.3%) requiring respiratory support with high flow nasal canula. All participants recovered well with the mean length of admission 4.36+/- 3.8 days. Treatment included supportive care including transfusion support, two (8.7%) needed simple transfusion, two (8.7%) needed exchange transfusion. Regarding the laboratory values, coagulations studies were noted to be elevated among all those obtained, but overall limited values were obtained. (Table 2) Thus far no complications of stroke, thrombosis, or pulmonary emboli are noted in the patients positive for COVID in sickle cell disease at our institution. No deaths were reported.Conclusion:Our population reflects what has been described thus far in other cohorts regarding patient demographics, clinical presentation and evolution of disease. Missing laboratory results is most likely due to the mild severity which did not require further clinical evaluation. The absence of VTE/PE may be explained by the low rate of ICU admissions. A similar ICU admission rate of 13% in the same age group as our population was described in a study conducted in France with 83 patients. [2] Compared to a study conducted in Detroit, Michigan, our population underwent comparable rates of transfusions with 3 patients compared to 4 in our population, again most likely due to the mild severity. [3]Our results reflect only MUSC's testing sites and we are dependent on patient's self-report which may not represent our entire population. To address this issue, as part of the Sickle Cell South Carolina network, we are partnering with two other institutions to assess SARS-Cov-2 infection in South Carolina.SARS-CoV-2 pandemic has brought to light many disparities encountered in the American health care system. It is premature to evaluate the immediate and long-term ramifications of COVID19 in individuals with sickle cell disease, due to which we plan to continue to monitor for the next 2 years.

Emergence of gram-negative organisms as the cause of infections in patients with sickle cell disease.

Patients with sickle cell disease are at higher risk of infections with encapsulated bacteria due to immature immune responses and functional asplenia. We aimed to study our patient population for the emergence of gram-negative organisms other than Salmonella as the cause of osteomyelitis and document a vast decrease in Streptococcus pneumoniae bacteremia rates. We conducted a retrospective chart review of 158 patients with sickle cell disease registered at our hospital. Over a period of 13 years, every patient presenting to the emergency department (ED) with fever had their medical record reviewed for blood cultures, wound cultures, and magnetic resonance imaging results for osteomyelitis. The number of patients presenting to the ED with fever was 105, with 581 febrile episodes and 893 blood cultures. Among those, no culture grew Streptococcus pneumoniae, 14 grew coagulase-negative staphylococci (1.5%), one grew Salmonella enterica Paratyphi B, and three grew Salmonella enterica group C (in the same patient). The total number of osteomyelitis episodes in patients with sickle cell disease presenting with fever and documented by imaging was nine (1.5%). In patients with osteomyelitis, organisms were isolated in four patients (44%), including Enterobacter cloacae, Bacteroides, Pseudomonas aeruginosa, and Salmonella enterica group C. Immunization against Streptococcus pneumoniae and the use of prophylactic penicillin has virtually eliminated pneumococcal bacteremia among our patients. We observed the emergence of gram-negative organisms other than Salmonella as the cause of osteomyelitis in patients with sickle cell disease.

Study of Common Infections among Children with Sickle Cell Anaemia In Saudi Arabia

Sickle cell disease (SCD) is a collective term for a number of genetic disorders in which hemoglobin is structurally abnormal, resulting in the episodic formation of sickle-shaped red blood cells (RBCs) and a wide range of clinical manifestations.Aims: To identify the common infections in children with sickle cell disease in Kingdom of Saudi Arabia regarding its prevalence, infection sites, as well as type of pathogens.Methods and Material: This was cross-sectional study conducted on 100 sickle cell disease patients who attended emergency department, King Abdulla Hospital, KSA. All children with SCD presenting with symptoms and signs suggestive of infections or acute complications of sickle cell anaemia were included e.g. fever, cough, pain, burning micturition, swelling, bonny tenderness. The identification of the infecting organism was done by culture studies.Results: Patients' age ranged from 2 to 18 years old with a mean of 13.12±4.85 (SD); 68 patients were females and 32 were males while, 95% of patients had positive family history of consanguinity. Nine (9%) and 12 (12%) cases had positive blood and urine cultures. Out of the 21 positive microbial infection cases, 12 cases were diagnosed as Urinary Tract Infection, 4 cases as Osteomyelitis, 2 cases as Fever for investigation and 3 cases as Sepsis. All cases of pneumonia were diagnosed clinically (no positive microbial blood culture cases). Two of the Osteomyelitis cases were Staphylococcus species and the other 2 were Salmonella. In all cases diagnosed as Fever for investigation and Sepsis, the organism was Staphylococcus species. In cases diagnosed as Urinary Tract Infection; 7 of them were E. coli and 5 were Klebsiella pneumonia. Conclusions: Urinary tract infection was the most common infection in our study. E. Coli was the most common organism isolated followed by Staphylococcus species, Klebsiella pneumonia and Salmonella spcs

Quality of life assessments in a cohort of Mozambican children with sickle cell disease.

Introductionsickle cell disease (SCD) has significant pediatric morbidity and mortality in sub-Saharan Africa, where access to therapies such as hydroxyurea and opioids is often limited. Poor disease control and Pain management adversely affects the well-being and mental health of affected children. Questionnaires have been utilized in other regions to report the quality of life (QOL) in children with SCD, but assessments from Africa are lacking.Methodschildren age 2-14 years with SCD presenting for routine outpatient consultations at Hospital Central de Maputo from June-August 2017 were offered participation. After informed consent, the Pediatric QOL Inventory (PedsQL) SCD Module was administered to all caregivers and children > 5 years. Responses were scored from 0-100, with higher scores representing better QOL.Resultsa total of 14 children were included, with six (43%), four (29%), two (14%), and two (14%) from the age groups of 2-4, 5-7, 8-12, and 13-14 years, respectively. Mean overall patient QOL was 65.3 and 56.0 in child and caregiver respondents. In patients > 5 years, the difference in mean overall QOL for those on/not on hydroxyurea was 0.6 (66.5-64.9) in child respondents and 15.8 (68.4-52.6) in caregiver respondents. Domains related to worry/emotions and communication scored lower in QOL than Pain-related domains for both patient and caregiver respondents.ConclusionSCD has a negative impact on QOL as reported by this cohort of Mozambican pediatric patients and caregivers, with Pain being less of a concern than emotional and interpersonal issues. A comprehensive, child-focused care approach with robust psychosocial support is needed.

Respiratory pathogens and acute chest syndrome in children with sickle cell disease

BackgroundAcute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not...

Administration of analgesics at home for the treatment of vaso-occlusive crises before admission to hospital

Introductionles crises vaso-occlusives (CVO) constituent le principal motif de consultation et d´hospitalisation chez les enfants drépanocytaires et nécessite le plus souvent une prise en charge à domicile avant l´arrivée en consultation. Le but de cette étude était de décrire l´attitude thérapeutique à domicile des enfants drépanocytaires reçus en consultation pour des CVO.Méthodesil s´agissait d´une étude transversale descriptive et analytique, qui s´est déroulée aux urgences pédiatriques du Centre Mère et Enfant de la Fondation Chantal Biya sur une période de 4 mois allant de février à mai 2018. Nous avons procédé à un échantillonnage consécutif. Tous les patients drépanocytaires venus consulter pour CVO ont étés inclus.Résultatscent cinquante-deux patients ont été enrôlés dans l'étude. La tranche d´âge la plus représentée était celle de 5-10 ans. Quatre-vingt-deux patients (54%) arrivaient plus de 24h après le début des crises et 70 (46%) dans les 24 premières heures; 80% (n=122) de notre échantillon avaient eu un traitement antalgique à domicile. Nous avons retrouvé une escalade thérapeutique dans 31,2% de cas. Le recours aux médicaments de la prescription médicale (75,4%, n=92) prédominait au 1er recours. La posologie des antalgiques n´était pas correcte dans 67% de cas (surdosage dans 70% des cas). Seul 33% des antalgiques utilisés à domicile étaient administrés à de bonnes posologies.Conclusionl´étude démontre que la prise en charge des CVOs par les patients à domicile est inadéquate. Des mesures doivent être prises pour garantir que tout patient drépanocytaire puisse gérer efficacement les CVOs mineures à modérées à domicile.

Primary pigmented meningeal melanocytoma originating in Meckel cave in a patient with carney complex

Rationale:Primary melanin-producing tumors are rare extra-axial neoplasms OPEN of the central nervous system. In the literature, few case reports have discussed neoplasms involving the cavernous sinus; of these, only 4 have reported on neoplasms originating in Meckel cave. The diagnostic approach, including clinical and radiological analysis, is challenging, and cytopathological assessment with a molecular basis is the best approach to discriminate between these lesions. Herein, we discuss the pathophysiology, diagnostic approach, intraoperative features, and postoperative management in a unique case of primary pigmented meningeal melanocytoma originating in Meckel cave in a patient who was diagnosed with Carney complex (CCx) and sickle cell disease (SCD).Patient concerns:A 23-year-old man diagnosed with SCD had also been diagnosed previously with CCx, without any familial history or neurocutaneous melanosis. He had experienced headaches accompanied by left facial pain and paresthesia for 2 months.Diagnosis:The initial computed tomography scan and magnetic resonance imaging (MRI) revealed a mass arising from the left Meckel cave. On MRI, it followed the signal intensity of melanin. He underwent subtotal resection of the mass. Considering the patient's history of CCx, melanocytic schwannoma was the most relevant diagnosis. A postoperative histopathological examination was suggestive of benign pigmented meningeal melanocytoma.Interventions:The patient underwent an uneventful subtotal resection of the mass through a left temporal linear incision.Outcomes:The patient showed progressive improvement of neurologic deficits, and after 2 years of follow-up, he did not present with any new complaints.Lessons:To the best of our knowledge, this is the first report of the unusual presentation of both SCD, as well as of primary pigmented meningeal melanocytoma in a patient with CCx. Complete surgical resection can be curative in most cases of melanocytoma. The presence of CCx with SCD suggests potential shared genetic contributions that will require further exploration.

Pharmacological interventions for painful sickle cell vaso-occlusive crises in adults.

Pharmacological interventions for painful sickle cell vaso-occlusive crises in adults.

The Effects of Utilization of Individualized Pain Plans in Treatment of Vaso-Occlusive Crises in the Emergency Department

Background Sickle cell disease (SCD) is an inherited blood disorder that affects millions of people worldwide, with approximately 100,000 Americans affected (Center for Disease Control, 2017). In the U.S., SCD results in over 200,000 emergency department (ED) visits annually, with pain as the most common complaint (Lanzkron S, et al 2010). At The Ohio State University (OSU) Wexner Medical Center, there is a comprehensive care center for patients with SCD. At their initial patient visit, the patient and their hematologist determine a customized pain plan to be enacted when they present to the ED in acute vaso-occlusive crisis (VOC). In January 2015, these plans were implemented to allow for more rapid treatment of pain crisis in the ED at OSU. Methods A multidisciplinary group was formed in order to accelerate the treatment of SCD patients who presented with VOC. The group's goal was to reduce the time to first opioid by utilizing individualized pain plans for each patient. This would reduce the amount of time deciding the best course of treatment. With reduction in time to first opioid, outcomes including overall length of ED stay, disposition, and length of inpatient admission were identified. Data regarding these endpoints were collected from 01/01/14 to 12/31/15. Generalized linear models were fit to compare the clinical outcomes pre and post implementation of the new protocol. Comorbidities were associated with outcomes using the same modeling technique, where univariable models were built and multi-test adjustment was performed through false-discovery rate (FDR). Results During the 2-year study period, 214 patients with SCD accumulated 2429 ED visits in total. The model estimated a 48% decrease in time to first opioid after implementation of the individualized pain plan protocol (p&lt;0.0001). There was also a decrease in the length of ED stay by 22% (p&lt;0.0001). No significant difference between the type of disposition (discharged to home, inpatient admission, eloping from ED, or leaving without being seen) was found. No difference was found between the average number of visits to the ED and the length of inpatient admission pre and post protocol. The data did reveal a 13% increase in length of ED stay in patients with comorbid kidney disease (FDR p=0.02) and a 12% increase in length of stay in the ED for patients with history of venous thromboembolism (VTE) (FDR p=0.04). Patients with history of VTE were also found to have a 39% longer hospital admission than those without (FDR p=0.05). The odds of getting discharged from the ED were 55% lower in patients with essential hypertension (FDR p=0.02) and they were 2 times more likely than patients without hypertension to be admitted to the hospital (FDR p=0.05). Conclusion Utilization of individualized pain plans for patients with sickle cell disease presenting with VOC results in a significant reduction in the amount of time to first opioid administration. Implementation of the protocol also led to a reduction in length of stay in the emergency department, however the probability of admission did not change. In examining the effect of comorbidities on clinical outcomes, patients with history of kidney disease or VTE had increased length of ED stay and those with history of VTE also had longer hospital admissions. Patients with comorbid essential hypertension were also twice as likely to be admitted to the hospital though length of inpatient admission did not change. It is possible that patients with kidney disease have worse disease as evidenced by end-organ damage due to repeated vascular insult, ischemia, and inflammation. Similarly, those with history of VTE may have higher viscosity, endothelial adhesion, and dysfunction leading to clots. Patients with comorbid essential hypertension can also be thought to have recurrent vascular damage leading to systemic hypertension. From this information, it can be concluded that utilizing individualized pain plans in SCD patients with VOC will lead to decreased time to analgesia and perhaps decrease use of healthcare resources. Disclosures Desai: Novartis: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; University of Pittsburgh: Research Funding; Ironwood: Other: Adjudication Board; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Potomac: Speakers Bureau.

Association of Time to Initial Emergency Department Analgesia with Rate of Admission in Patients with Uncomplicated Sickle Cell Disease Vaso-Occlusive Crises

Introduction Painful vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). When the pain cannot be managed with home analgesics, patients often present to the Emergency Department (ED) in order to obtain relief. In the ED, the patient may encounter barriers to care that include provider bias, prolonged time to initial analgesic, and inadequate opioid dosing. The goal of this retrospective, single-institution study was to evaluate whether there was an association between the time to initial analgesic and the rate of admission for patients with SCD presenting with VOC. Methods A retrospective, single-institution chart review of adult ED visits between January 29, 2019 and June 30, 2019 was conducted for patients with a history of SCD who presented to the Adult ED for pain related to a VOC. Patients were divided into two cohorts: patients with a calculated door-to-dose time of ≤ 2 hours and patients with a door-to-dose time of &gt; 2 hours. Registration time, time of first opioid administration, and disposition decision were recorded for each visit. The primary outcome of interest was to compare the rate of admission between the two cohorts. Results During the study period, 43 unique patients met the inclusion criteria. These patients were seen for a total of 264 visits for VOC-related acute pain. The overall rate of admission was 49% (130 of 264). The cohort of patients receiving analgesia within 2 hours included 75 (28% of total) subjects, whereas 189 (72%) patients received their first analgesic dose after 2 hours. The admission rate for patients with a door-to-dose time ≤ 2 hours was not significantly different from that for patients with a door-to-dose time &gt; 2 hours (40% vs 53%, P = 0.076) A subgroup analysis was performed on patients presenting to the ED with uncomplicated VOC. This analysis excluded any visits in which patients presented for pain with additional complications (e.g. fever, chest pain, nausea/vomiting, shortness of breath). The purpose of this exclusion was to control for possible confounding by severity or complexity of illness, given that patients who have higher acuity are more likely to be seen faster, but also more likely to be admitted. A total of 47 patient visits from 23 unique patients were excluded from the total visits to perform the subgroup analysis. The most prevalent reasons for exclusion included URI (n=7), nausea and vomiting (n=7), shortness of breath (n=7), and fever (n=7). A subgroup of 37 patients was seen for a total of 217 visits for uncomplicated, VOC-related acute pain. The overall rate of admission was 46% (100 of 217). In 61 (28%) of the encounters analgesia was administered within 2 hours of registration, whereas in 156 (72%) of the encounters the first analgesic was received after 2 hours. In this subgroup of patients presenting with uncomplicated VOC, the admission rate for patients with a door-to-dose time ≤2 hours was significantly lower than that for patients with a door-to-dose time &gt; 2 hours (33% vs 51%, P = 0.016). Conclusion For the entire cohort of patients with sickle cell disease, the administration of analgesia within 2 hours did not result in a statistically significant decrease in rate of admission. In the subgroup analysis, which excludes VOC-related pain visits with complications, the administration of analgesia within 2 hours did result in a statistically significant decrease in the rate of admission. This demonstrates the association between rapid administration of analgesia and a greater likelihood of discharge in the setting of uncomplicated VOC. Based on these preliminary findings, it would be reasonable to allocate additional resources to ensure the rapid administration of analgesia in patients with uncomplicated acute VOC pain crises. Disclosures Dupont: Pfizer: Other: Grant Support. Baer:Al Therapeutics: Research Funding; Incyte: Research Funding; Abbvie: Research Funding; Takeda: Research Funding; Kite: Research Funding; Forma: Research Funding; Astellas: Research Funding. Wilkerson:Pfizer: Other: Grant, Research Funding; Roche: Research Funding; Coaptech: Research Funding; Provay Pharmaceuticals: Research Funding; Cepheid: Other: Research Equipment; Janssen: Research Funding.

360o View of a Day Hospital Program Performing Exchange Transfusion and Outpatient Pain Management on Adults with Sickle Cell Disease

Purpose: Therapeutic erythrocytapheresis, known also as automated red blood cell exchange transfusion (RBC exchange), is standard of care for patients with sickle cell disease (SCD) presenting with severe complications and for primary prevention of CNS events in those with increased risks. There is limited data on the framework and experience of performing this procedure in a large adult population and even less on challenges and outcomes. Here, we present demographic and statistical data highlighting characteristics of the chronic exchange transfusion program at a comprehensive and multidisciplinary adult SCD center. Methods: Data were collected from adults (18 years and older) with a diagnosis of SCD that were receiving blood transfusions in the outpatient treatment facility from September 1st, 2017 to August 31st, 2018. Data gathered included age, gender, procedure indications and frequency, hemoglobin S percentage (Hb S%), target pre and post Hb S%, ferritin trend, and type of intravascular device used for procedure. Three hundred and forty-four (344) episodes of transfusions, were performed in 52 unique patients, corresponding to 21 % of the unique patients treated at our center during that period. Two hundred and sixty-two (262) of the transfusion procedures were RBC exchanges. These RBC exchanges were performed in 35 (14%) of the unique patients. Since a sizable proportion of our patients received pain treatment during RBC exchange, we explored how the pain visual analog score (VAS) changed while undergoing pain treatment during RBC exchange and in relation to multiple opiate doses. Descriptive and basic statistical analysis were performed on the data obtained for those receiving RBC exchange alone or in combination with pain management. Results: Thirty-five unique patients underwent RBC exchange during the study period. All but two (2) patients had the procedure via an implanted dual lumen Vortex port, one (1) by an arteriovenous fistula and one (1) via his native veins. Most of the RBC exchanges were performed as part of a chronic transfusion program for one of the following indications: primary prevention of stroke; secondary prevention of stroke; recurrent acute chest syndrome (ACS); intractable pain; presence of multiple comorbidities including pulmonary hypertension, chronic kidney disease and intractable leg ulcers. One patient received RBC exchange in preparation for bone marrow transplant. The three (3) other patients that only received one (1) RBC exchange during that period were previously on exchange transfusion but discontinued the procedure due lack of venous access or benefit from the procedure. The frequency of RBC exchange varied depending of the patient's specific indication for the procedure and the ability to reach a target Hb S% goal of &lt; 30%. The RBC exchange occurred in patients as frequently as every four (4) to seven (7) weeks. The number of transfusions per patient/year ranged from one (1) to thirteen (13) with a mean and median of eight (8). Number of RBC units used per procedure ranged from four (4) to thirteen (13) with a mean of eight (8.6), with each unique patient usually receiving the same amount. Twenty-three (66%) unique patients received, at least once, acute pain treatment - oral, intravenous, or a combination during RBC exchange. The mean change of VAS between presentation and end of the pain management period was 1.9 (p&lt;0.0001). Conclusion: Our data shows that therapeutic RBC exchange are performed on a regular basis on a small but significant subgroup of patients living with SCD and treated at a comprehensive SCD center. Intravenous opioid management of acute pain can be effectively performed while receiving RBC exchange which provides patients with multimodal interventions in the outpatient setting. The relationship between change in VAS and concurrent transfusion deserves further investigation. Although there are standard indications for RBC exchange, we and others use it for indications for which there is low level of evidence or no evidence of efficacy (i.e. leg ulcers). We found that there great variability on the frequency of the procedure, total number of RBC exchanges per year and number of RBC units used. Prospective studies are needed to better understand the short and long-term effects, complications and outcomes of chronic RBC exchange in adults living with SCD. Figure Disclosures Kato: Bayer: Research Funding; Novartis, Global Blood Therapeutics: Consultancy, Research Funding. De Castro:Pfizer: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Optimizing the Economic Impact of Sickle Cell Hospitalization By Effective Care Plans

Background: Adults with sickle cell disease (SCD) vaso-occlusive crisis (VOC) frequently seek care in the emergency department (ED) which often results in hospital admissions. The Hematology-Oncology at Ellis Fischel Cancer Center collaborated with organization's ED to develop and implement individualized care plans for adults with SCD presenting to the ED with the goal of adequate outpatient management, reduction in hospital admissions and optimizing the economic impact of sickle cell hospitalization. Methods: Baseline data was collected from November 2014 through June 2018. Medical Director, Oncology Unit Manager, and Performance Improvement Professional (PIP) collaborated with the ED Medical Director and representatives to develop a disease-specific individualized acute care plan for our adult SCD patient population. 100% case were reviewed by PIP and bi-monthly aggregate case review were done by the Medical Director/Unit Manager. The care plan include pathways for lab collection, pain medication regimens, prescription opioid refill policies, a timeline for outpatient follow-up, and criteria for hospital admission. These care pathways were then transitioned to order sets within the organization's electronic medical record. Results: Implementation of the SCD care plans resulted in significant improvement of length of stay(LOS) index indicating better management during the hospital stay, resulting in reduction of the inpatient pharmacy cost per encounter in half as mentioned in Table 1. Admissions per patient did not change significantly, but ED visits per patient went down and clinic visits per patient went up pointing to better management outside of acute care as shown in Table 2. Last 4 quarters of this study showed marked decrease in cost per patient as indicated in Table 3. Conclusions: This study clearly demonstrates that collaboration with the ED and development of care plans can improve the overall patient care for this population resulting in better outpatient management. Implementing this protocol has not only improved the patient experience but also has decreased the financial toxicity for the patient and the institution. We would encourage other institutions to implement such protocol in the ED and in the outpatient setting to meet the patient needs. Table 3 Disclosures No relevant conflicts of interest to declare.

INHOSPITAL OUTCOMES OF MYOCARDIAL INFARCTION IN SICKLE CELL DISEASE

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Sickle cell disease (SCD) has been associated with considerable morbidity and mortality, including a higher risk for ST VS elevation myocardial infarction (STEMI). These patients often have few or no traditional risk factors for coronary artery disease, and risk stratification tools, such as the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) models place these patients at low risk. The mechanism of MI in SCD is not exactly known, as coronary angiography is often normal. However, the effect of SCD on outcome in patients with myocardial infarction remains unclear. We hereby report the in-hospital mortality in patients with SCD presenting with STEMI compared to the general population. METHODS: The National Inpatient Sample (NIS) dataset was queried from 2003 to 2014 to identify the primary diagnosis of STEMI (ICD-9 code: 410.x0, 410.x1,410.x2) among hospitalized patients. Among this patient population, we identified patients with SCD (ICD code: 282.41, 282.42, 282.6x) as a coexisting medical condition that is not directly related to the principal diagnosis. Categorical and continuous variables were tested using Chi-square test and Student t-test respectively. Multivariate regression was used for the analysis of primary outcomes of interest. RESULTS: Among 2,174,960 patients with STEMI only 120 patients were found to have SCD (0.005%). compared to the general population, patients with SCD were significantly younger (50 years vs. 63.4 years, p<0.001), were more likely to be female (56.7% vs. 32.8%, p=0.001) and, non-white (91.4% vs. 20.9%). Patients with SCD were found to have a higher prevalence of fluids and electrolyte disorders (45.38% vs 14.8%, p<0.0001), renal failure (19.11% vs 7.37%, p<0.0001), anemia (19.7% vs. 9.8%, p<0.0001) and, substance abuse (7.56% vs 2.07%, p<0.001). In terms of in-hospital outcomes, we found that the mean LOS (4.46 days vs 4.71, p =0.82) and cost ($68,866.00 vs $69,600.00, p= 0.96) were not significantly different between patients with SCD versus those without. However, the in-hospital mortality rate was higher among patients with SCD with STEMI (10% vs 7.07%, p= <0.001). Furthermore, the trend of SCD patients presenting with STEMI is largely unchanged while the trend for general population is generally down trending. CONCLUSIONS: Patients with SCD have a higher in-hospital mortality compared to the general population when presenting with STEMI. CLINICAL IMPLICATIONS: Given that patients with SCD are more likely to present with atypical clinical features making the diagnosis of STEMI difficult, and therefore delaying timely intervention; it is imperative that physicians are adept at recognizing this presentation in SCD patients. DISCLOSURES: No relevant relationships by Kathir Balakumaran, source=Web Response No relevant relationships by Aakash Desai, source=Web Response No relevant relationships by Arish Noor, source=Web Response No relevant relationships by Varun Tandon, source=Web Response

Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date.

Sickle cell disease (SCD) is one of the most common inherited blood disorders globally. It is a grouping of autosomal recessive genetic disorders identified by a genetic mutation that replaces glutamic acid with valine at the sixth amino acid on the hemoglobin β-globin chain. Millions of people around the world live with a severe genotype of SCD that is often associated with occlusion of the microvasculature resulting in episodes of severe pain and multiple organ system dysfunction. These episodes, commonly categorized as vaso-occlusive crises (VOC), are a distinctive clinical presentation of SCD which represents the majority of SCD morbidity and associated hospitalizations. Though the complete process by which these crises occur is complex and not fully outlined, evidence reveals this process to be multifactorial and heterocellular. For nearly two decades, hydroxyurea was the only FDA-approved therapy for SCD. Evidence to date shows that hydroxyurea treatment significantly reduces the rate of VOC, hospitalizations, and mortality. Despite these benefits, adherence remains problematic due to a variety of adverse effects and interpatient variability connected with hydroxyurea therapy. Crizanlizumab, an adhesion inhibitor of sickled red blood cells, was recently granted breakthrough therapy designation. Results of a phase 2 study have reported a successful reduction in annual rates of vaso-occlusive crisis with a favorable safety profile. This paper reviews the available literature concerning crizanlizumab use in patients with SCD.

Randomized genetic polymorphism analysis of sickle cell disease patients in a tertiary care teaching hospital Bhubaneswar

Sickle cell disease or HbSS genotype is associated with the most severe, most frequent pain and shortest life expectancy. However, the genetic modifiers play a very important role which result in extremely diverse clinical severity. This study is intended to analyse the hereditary polymorphism in 25 patients diagnosed as Sickle cell disease (SCD) presenting in a tertiary care hospital of Eastern India. The subjects were diagnosed as SCD based on clinical examination, hematological investigation, hemoglobin electrophoresis, parental screening by Hemoglobin electrophoresis and molecular diagnosis. Blood samples from 25 patients of diagnosed SCD were analysed. The whole DNA isolation was pursued and gene specific PCR amplification were performed. The amplified products were purified and sequencing was done. From the sequence information, the phylogenetic examination and sequence connected study was performed. The outcomes demonstrated a specific single band in 25 DNA amplified PCR item after agarose gel electrophoresis. The phylogenetic examination uncovered that some of the sequence were highly diverse and some of them also found in a single monophyletic clades. The sequence information linked with the goblin chain can be utilized in various fundamental and applied research in sickle cell anemia and furthermore in other hemoglobinopathies.

PS1524 WHEN IS A CT NEEDED TO DIAGNOSE ACUTE PULMONARY EMBOLISM IN INDIVIDUALS WITH SICKLE CELL DISEASE

Background:Sickle cell disease (SCD) is a hypercoagulable state that results in an increased incidence of thromboembolic events including deep venous thrombosis and pulmonary embolism (PE). However, the diagnosis of acute pulmonary embolism (APE) in individuals with SCD is more difficult due to other potential pulmonary complications such as acute chest syndrome, vaso‐occlusive pain, or an exacerbation of pulmonary hypertension. A D‐dimer is also unreliable in SCD as it is often elevated at baseline. Validated diagnostic tools, such as the Wells criteria are used to determine the likelihood of a healthy person (without SCD) having an APE but these have not been tested in individuals with SCD. Instead, adults with SCD who present to the hospital with chest pain often undergo lung imaging as the first line test although many other pathologies could mimic the presenting symptoms of an APE. Thus, there is often unnecessary exposure to radiation and intravenous contrast for individuals with SCD presenting with chest symptoms in the acute setting.Aims:The primary aim of this study was to evaluate the positive predictive value of the Wells criteria in predicting APE in SCD using a retrospective cohort to potentially identify a new, more specific diagnostic algorithm.Methods:This is a retrospective case cohort study. Index cases were individuals with SCD (confirmed) who underwent a CT of the chest with IV contrast (to assess for a pulmonary embolism) in the emergency department, outpatient clinic or inpatient setting from January 1, 2013 to October 1, 2017. Each encounter was evaluated for demographic data, presenting symptoms, laboratory assessments, final diagnosis and scored using the Wells criteria. Charts were excluded if CT scans were obtained for any other reason than to evaluate for APE or if the patient had did not have SCD.Results:There were 349 charts that fit the inclusion criteria. Most individuals were &gt; 18 years (97%) and female (62%). HbSS was the most common phenotype (80%), followed by HbSC (15%) and HgbS‐Beta thalassemia (6.5%). The overall incidence of APE was 9.7%. The most common final diagnosis was vaso‐occlusive crisis (60%) and/or acute chest syndrome (18%). For patients in this cohort with an APE, the average Wells score was 5.14 (p &lt; .001). Evaluating specifics of the Wells criteria, “signs and symptoms of a DVT” and “PE most likely diagnosis” were additionally statistically significant in determining an APE (p &lt; .020 and p &lt; .001). HbSS genotype (p &lt; .030) was also statistically significant. There was no statistical difference between cases and controls for oxygen saturation, heart rate, hemoglobin, shortness of breath, age or sex. A Wells score &gt;4 provided the best sensitivity (73.5%) and specificity (72%) in our sample. A Wells score of &gt;/5 caused the sensitivity to decline significantly, making the three‐tier model less effective in our population.Summary/Conclusion:The Wells criteria can adequately predict who should undergo a CT with IV contrast to evaluate for APE. When using the Wells criteria, the two‐tier model allowed for the best sensitivity and specificity in our population. Logistic regression analysis did not reveal any variables that increased the sensitivity or specificity to a more specific algorithm than what was attained with the Wells Score. This study is being replicated at other institutions with large sickle cell populations to validate these findings.