Sickle Cell Crisis Research Articles

Sickle Cell Eye Disease

SCD commonly causes visual problems. It can affect all parts of the eye, as the abnormally shaped blood cells can occlude of any small vessel in the body. The crescent shaped red blood cells affect the oxygen carrying ability of blood. Therefore, SCD affects all major organs such as the spleen, lungs, heart, kidneys, liver and eyes. As a consequence, patients with SCD can suffer from a widespread of serious pathologies such as: chronic anaemia, stroke, chest pain, tissue necrosis, shortness of breath, kidney damage, recurrent infections and painful sickle cell crises.

Sudden Death in Diabetic Ketoacidosis Complicated by Sickle Cell Trait.

In a sudden death investigation of a service member with sickle cell trait (SCT), evidence of sickle cell crisis further complicated by coexisting, undiagnosed diabetic ketoacidosis called into question the synergistic effects of diabetic ketoacidosis on red blood cell sickling. Sickle cell trait affects more than 4 million people in the United States (US) with the highest prevalence in non-Hispanic Blacks (7%-9%; Mil Med 2017;182(3):e1819-e1824). The heterozygous state of sickled hemoglobin was previously considered a benign condition causing sickling during hypoxic, high-stress conditions such as exercise and high altitude ( Am Assoc Clin Chem 2017). However, research within the last decade shows evidence of sudden death among SCT patients ( J Forensic Sci 2011;56(5):1352-1360). It has been shown that the presence of sickled hemoglobin artificially lowers levels of hemoglobin A1c making it a less effective biomarker for red blood cell glycosylation over time in sickle cell patients ( JAMA 2017;317(5):507-515). The limited scope of medical understanding of the effects of SCT in combination with other comorbidities requires further investigation and better diagnostic criteria. The uniqueness of the US Military and its screening program for sickle cell disease (SCD) and SCT allows for more detection. Since May 2006, newborn screening for SCD/SCT has been a national requirement; however, anyone older than 14 years may not know their SCD/SCT status ( Semin Perinatol 2010;34(2):134-44). The previous absence of such national screening makes it more challenging to identify SCT and SCD patients even within high-risk populations. Furthermore, patients may not know or understand the results of their SCD/SCT status testing. International standards for the autopsy of decedents with SCD and SCT exist ( R Coll Pathol 2017). Within the US, testing of vitreous electrolytes is a common practice in suspected natural death cases, but a review of the US literature did not demonstrate any autopsy standards or recommendations for persons with SCT or high-risk persons for sickling pathologies. The identification of a new diagnosis of type 2 diabetes mellitus, as the cause of death, is not uncommon; however, this case indicates that type 2 diabetes mellitus was not the sole contributing factor. It further illustrates that the US may be underestimating the impact of SCD and SCT as a cause of death, a contributing factor to death, and its synergistic effects with other pathologic processes. We propose a stringent literature review in conjunction with a review of international autopsy standards to develop national autopsy standards and possible SCT/SCD screening recommendations for high-risk persons at the time of autopsy.

Sickle cell disease and COVID-19 in pregnant women

IntroductionThe effect of coronavirus disease (COVID-19) on pregnancy outcome in women with sickle cell disease (SCD) is unknown. ObjectivesTo analyze the severity of the SARS-CoV-2 infection in pregnant women with SCD and its impact on pregnancy. MethodsThis retrospective cohort study included SCD pregnant women tested positive for COVID-19 between March 2020 – February 2021. The primary endpoint was the severity of the COVID-19 infection. Secondary endpoints were pregnancy complications and fetal outcomes. ResultsDuring the study period among 82 pregnant women with SCD, 8 have presented symptoms suggestive of COVID-19 and were tested positive. A common mild clinical presentation was observed in 6 women (75%), one woman was asymptomatic and one required oxygen. The latter was admitted to the Intensive Care Unit and a cesarean section was performed in the context of an ongoing vaso-occlusive crisis and acute chest syndrome together with incidental preeclampsia. Labor was induced in another patient who developed a vaso-occlusive crisis after COVID-19 remission. Fetal outcomes were good with an average Apgar score of 10 and normal umbilical blood pH at birth. Two newborns were small-for-gestational-age as expected on the ultrasound follow-up before occurrence of COVID-19. ConclusionCOVID-19 infection in our population of pregnant women with SCD had typical presentation and rarely triggered a sickle cell crisis or other complications. Fetal outcomes were good and did not seem to be directly influenced by the SARS-CoV-2 virus. Further studies are required to confirm these observations as compared to the population of women with SCD without COVID-19 infection.

Evaluation of the Anti-Sickle Cell Activity of Uvaria Chamea P. Beauv. Roots Aqueous Extract

Sickle cell disease was a very common hemoglobinosis in tropical countries. Several plants were used in traditional Beninese medicine to relieve sickle cell crises. The present work was carried out to test the efficiency of Uvaria chamea roots aqueous extract in the treatment of sickle cell crises.
 
 Methods: Uvaria chamea roots aqueous extract was preincubated at different concentrations with blood cells from SS red blood cells before or after the Emmel Test. Intra-erythrocyte oxidative stress was measured by methaemoglobin assay after incubation of the extract with hemoglobin. In vivo, the action of the extract on Hemoglobin level, Mean Corpuscular Volume, and platelet count was measured in Wistar rats.
 
 Results: The extract significantly prevented the formation of sickle cells at doses of 40 and 20 mg / ml of blood (P <0.05) and significantly reduced sickle cells to the normal biconcave form at the dose of 40 mg / ml (P <0.05). It lowered the production of methemoglobin at a dose of 10 mg / ml, suggesting antioxidant activity. Hemoglobin level, Mean Corpuscular Volume, and platelet count did not significantly increase in treated rats, indicating that the extract did not stimulate erythropoiesis or thrombopoiesis.
 
 Conclusion: Uvaria chamea extract inhibited dose-dependent sickling of red blood cells. It reduced intraerythrocyte oxidative stress but did not show hematopoietic activity. It could therefore be considered in the preventive or curative management of sickle cell crises, but not against anemia.

(Lack of) knowledge of mothers about sickle cell trait and disease: a qualitative study.

to analyze the understanding of mothers about sickle cell disease and/or trait of the family from a diagnosed child. this is a qualitative study, using a semi-structured interview with 23 mothers, at a sickle cell disease outpatient clinic of a public institution, from October to December 2017. Analysis was thematic. all participants had sickle cell trait as well as the parents of their children. Twenty children were diagnosed with sickle cell disease by Heel Prick Test, and three, after hospitalization due to the disease. Most did not know how to report the presence of the trait or disease in relatives other than nuclear. diagnosis cannot be restricted to the result of neonatal screening, requiring that preventive information on sickle cell crises be reinforced. It is recommended to search for other affected relatives to learn about their genetic condition, reflecting on their reproductive decisions.

Haemoglobin (Hb) Genotype Profile in COVID-19 Disease Susceptibility and Severity in Lagos State Nigeria

COVID‐19 pandemic has posed unique challenges to the health providers involved with chronic diseases like Haemoglobin disorders (sickle cell disease). Therefore, this study highlights the susceptibility and severity of COVID‐19 associated with normal and haemoglobin variants. This study is a case series that includes patients evaluated between June and August 30, 2020, and diagnosed with COVID-19 by the Quantitative Polymerase Chain Reaction method. Alkaline haemoglobin electrophoresis was used to identify types of Haemoglobin genotype associated with mild-to-severe cases of COVID-19. A total of 697 COVID-19 patients were included in this study, with a mean age of 41.32 (12.917). There were more males (66.1%) than females. The most frequently detected genotype was AA (75.8%), followed by AS (22%). Severe conditions of COVID-19 were present in patients with HBAC 2(14.28%) and HBAS 13 (8.5%). Co-morbidities were present in (24.0%) of the patients, with a mortality rate of 1.3%. Patients with pneumonia in association with other co-morbidities are 26 times more likely to have severe SARS CoV-2 than those with only pneumonia, irrespective of their haemoglobin genotype profile. The clinical course is seen in normal haemoglobin, and the variant with COVID-19 was the same. It is suggested that people with haemoglobin variant are not at increased risk during COVID-19 infection or risk of a sickle cell crisis.

New Prescriptions After Hospitalization: A Bitter Pill or Just What the Doctor Ordered?

New Prescriptions After Hospitalization: A Bitter Pill or Just What the Doctor Ordered?

Performance of Neutrophil-to-Lymphocyte Ratio (NLR) in Differentiating Vaso-Occlusive Crisis from Infection in Patients Presenting with Sickle Cell Crisis

Background:Patients with sickle cell disease (SCD) are at increased risk of developing serious infections as a result of functional asplenia and altered humoral immunity. Nevertheless, presenting symptoms of sepsis such as fever and arthralgias are common in SCD and can occur with many sickle cell related conditions, including vaso-occlussive crises (VOC) and may not correlate with true infections. The neutrophil-to-lymphocyte ratio (NLR) is calculated as the absolute neutrophil count divided by the absolute lymphocyte count and represents an easily accessible value that has been found to correlate with inflammation and prognosis in several conditions. Few studies have evaluated NLR as a biomarker in sickle cell disease, and its utility in differentiating infection vs. VOC in patients presenting to the emergency room remains unknown.Method: We conducted a retrospective review of 143 patients with SCD who presented to the emergency department with fever and painful crises. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=92) and patients with proven/possible infection (n=51). Inclusion criteria for both groups were patients with SCD, 17 years and older and complete blood count with differential on presentation; patients who had received antibiotics prior to presentation were excluded. Data collected on presentation included genotype, age, gender, complete blood count, hydroxyurea use. Data was analyzed between the two groups using descriptive statistics and receiver-operating characteristic (ROC) curve analysis.Results: Demographics and clinical characteristics are summarized in the Table. The sample included primarily young adult males with 61% on hydroxyurea. Genotype HbSS (73%) was most prevalent followed by HbSC (23%) and HbSβ (4%). The mean Hb was around 8 g/dL. The VOC group had a lower mean white blood cell (WBC) count of 13.6, compare to 17.2 for patients with proven/possible infection. ROC analysis showed that NLR did correlate with infection, with a modest AUC 0.7 [95% CI (0.59-0.77)] that was significant (p=0.0002) when compared to the AUC=0.5 model. Maximum specificity and sensitivity in this sample was achieved with NLR = 4.5 (Specificity 75% and Sensitivity 59%).Conclusion: In this sample, NLR on presentation significantly but only modestly correlated with infection as opposed to VOC. Optimal performance at NLR=4.5 achieved Specificity 75% and Sensitivity 59%. Despite modest performance, given the widespread availability and cost-effectiveness of NLR testing, further study in a larger sample may derive other variables that can combine with NLR to formulate a predictive model to improve care for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Living Beyond Life Expectancy: Experience with Aging for Older Adults with Sickle Cell Disease

▪BackgroundOver the last five decades, advancements in management of sickle cell disease (SCD) have led to more individuals living beyond the median life expectancy, which has historically been 14 years based on autopsy data in 1973, to approximately 40 to 45 years in population-based studies and 61 years in recent cohorts from comprehensive programs. Despite the increasing life expectancy for people with SCD, there is a paucity of literature on the unique experiences of older adults with SCD (age > 50). This limits providers' understanding of how to address the unique needs of older adult patients with SCD as they age. Thus, the purpose of this study was to describe experiences with aging for older adults with SCD.MethodsWe recruited 19 older adults with SCD (age > 50) from a single academic comprehensive SCD center in the Southeastern United States. We conducted semi-structured qualitative interviews by phone and in person. Participants were asked open-ended questions about their experiences living with SCD, aging, and surviving beyond the SCD life expectancy. Audio-recorded interviews were transcribed verbatim. The transcripts were analyzed using conventional content analysis.ResultsThe mean age of participants was 58 years (range 50-71) and 47% (n=9) were female. The majority of participants were married or had a domestic partner (58%, n=11) and 47% (n=9) were working. Most participants had HbSS genotype (53%, n=10), 37% (n=7) had HbSC, and 11% (n=2) had HbSβ+-thalassemia. Most people reported current use of hydroxyurea (58%, n=11) and their most common chronic complications were avascular necrosis (79%, n=15), retinopathy (58%, n=11), and chronic kidney disease (47%, n=9).Participants described their experiences aging and living beyond the life expectancy for SCD, encompassed in three themes (Figure 1):Theme 1 was “challenges with SCD across the lifespan,” which focused on obstacles participates described from youth to adulthood, including experiencing pain and complications of SCD, but not being diagnosed with SCD until later in their childhood or until as late as mid-life. They described multiple obstacles as an older adult with SCD, including challenges maintaining employment, limitations in physical and social activities, and additional health problems such as kidney disease, increased fatigue, and pulmonary complications. They also reported perceiving healthcare providers were not knowledgeable enough about SCD to properly care for them.Theme 2 was “knowledge and self-management of SCD improves with age,” where participants described differences between being younger vs. older with SCD, including sharing lessons they learned over time about managing SCD, which made them feel more knowledgeable about how to care for themselves in their older age. They described strategies that helped prevent and manage pain crises, such as preparing for weather extremes, learning personal triggers for sickle cell crises, knowing when to rest and when to keep moving, hydration, and being proactive with their SCD care.Theme 3 was “surpassing life expectancy,” where participants discussed how their expectations for their life expectancy changed throughout their lives, and how their life expectancy was influenced by their family members, healthcare providers, and personal experiences and beliefs. Participants described being told by doctors at a young age that they would not live past age 18; however, when they made it to adulthood, some participants conveyed how they stopped allowing their prognosis to influence their thinking. Instead, they chose to trust in God that they would live long. Most participants said that their faith in God and healthy lifestyle choices were the main reasons why they surpassed the life expectancy for SCD.ConclusionThese findings described the experiences conveyed by older adults with SCD about living beyond their expected lifespan. These data provide direction for providers to address areas of care that are most important to this older population and inform development of interventions to increase the knowledge of providers about SCD and health self-efficacy. The information these participants shared will also provide guidance for younger adults with SCD as they navigate the aging process and implement strategies that can support successful aging with SCD. [Display omitted] DisclosuresStrouse: Takeda: Consultancy.

A Resident-Led Quality Improvement Initiative to Optimize Care for Children and Young Adults with Sickle Cell Disease Vaso-Occlusive Pain with Intranasal Fentanyl in the Emergency Department

Background:Sickle cell disease (SCD) is an inherited blood condition that predisposes affected patients to severe vaso-occlusive (VOC) pain events. The NHLBI (last revised in 2014) and ASH guidelines (last revised 2020) recommend a door-to-first dose should be within 60 minutes vs. 30 minutes from registration, and reassessment and re-administration of medications should be every 30 minutes. Non-IV routes of administration, i.e. intranasal (IN) can facilitate rapid analgesic treatment. Recent studies have shown IN Fentanyl as an effective pharmacological strategy to treat vaso-occlusive pain episodes.Methods:This resident-led Quality Improvement specific aim was to reduce the meantime from check-in to first analgesic delivery to SCD patients with VOC presenting to the Pediatric Emergency Department (PED) by at least 20% during 12 months and to improve the overall care of SCD VOC in accordance to best practices.PDSA cycle methodology was utilized to identify root causes, countermeasures, and key drivers (Figure 1A). We implemented a SCD VOC clinical pathway for PED providers to utilize our enhanced and updated version of an electronic order set named “PED Sickle Cell Crisis Power Plan” that includes IN Fentanyl as first-line therapy for SCD VOC. IRB approval was obtained.PED nursing staff was trained to administer IN Fentanyl with a nasal mucosa atomizer. Exclusion criteria of patients with SCD with other ICD-10 diagnosis codes, i.e pain not associated with VOC. The main indicators were assessment-to-dose time; registration-to-discharge time; first dose-to-discharge time, and rate of VOC admissions. Data was collected by discrete-time stamps and statistically analyzed using Excel 365. The analysis compared baseline with initial PDSA cycles from December 2019 to February 2020, and from September 2020 to March 2021.Results:From September 2020 to February 2021, a total of 54 encounters for SCD VOC qualified clinically to receive IN Fentanyl. A total of 49 of these encounters received this medication, while 5 refused its administration.Patient demographics: Male-to-female ratio was 53% and 47%, respectively. The majority of the patients seen were adolescents (63% with ages between 12-21 years). African-American participants represented 88% and non-Hispanics 84%.After our interventions, 94% of encounters have documented pain reassessment in their electronic medical records. IN Fentanyl was first introduced in the PED in September 2020, and became the first medication to be administered in 94% of the encounters. The average length of stay in the PED was 269 minutes (4 hrs. with 29 minutes).The SCD VOC Clinical Pathway was used in 90% of the encounters and the SCD VOC Power Plan was used in 80% of them. From the total of encounters, 59% required admission to the floor for further pain management strategies.As shown in the control chart (Figure 1.B), the meantime from check-in to first analgesic delivery to patients with VOC presenting to the PED was reduced to under 40 minutes by February 2021.After the implementation of IN Fentanyl, there is an overall improvement of the waiting time for administration of medications of more than 70 minutes (from 138 min down to 67 minutes). Most importantly, 37% (18/49) of SCD VOC events were discharged after successful VOC pain management in the PED.Discussion:PED staff surveys demonstrated a lack of familiarity with current VOC guidelines and a standardized pathway. Medication refusal of IN Fentanyl was found to be related mostly to patient preference, poor knowledge about side effects, and parental fear for oversedation before our interventions.Conclusion:A multi-disciplinary team was formed to assist health care providers in the ED to deliver optimal care to patients with SCD based on the current evidence-based SCD VOC clinical pathway and efficient pharmacological intervention with IN Fentanyl.Standardized procedures to treat and reassess pain for SCD VOC patients in the PED resulted in check-in to first-dose time reduction by 47%. There was a consistent improvement in Length of Stay in the PED, which decreased more than 60 minutes (from 5 hrs. 21 min. to 4 hrs. 29 min).There is a significant improvement of quality in the care of VOC including 1. Pain scoring system. 2. Documented pain reassessment. 3. Use of a multidisciplinary reviewed protocol that includes PED SCD VOC clinical pathway, and an updated order set power plan with IN Fentanyl as the first line. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Five-Year Outcomes of Chronic Red Blood Cell Exchange Transfusion Program for Patients with Sickle Cell Disease, the Experience of University of Nebraska Medical Center

▪Background:Red blood cell exchange (RBCX) is an effective therapy in treatment of acute and chronic complications of sickle cell disease (SCD). It involves exchanging patient's red blood cells (RBCs) with donor RBCs to significantly lower hemoglobin S concentration without subjecting the patient to the risk of iron overload. The University of Nebraska Medical Center (UNMC) established a chronic RBCX program in November 2015, which cared for patients with multiple hemoglobinopathies. In this study, we aim to evaluate some of the outcomes of patients with SCD who joined the program.Methods:This is a retrospective study based on review of medical records of patients with sickle cell disease. We reviewed the health records of patients with SCD who were enrolled in the chronic RBCX program between 11/2015-8/2020 at UNMC. We included patients with SCD, regardless of age, who underwent RBCX in the outpatient setting during the study period. Data were collected to assess if RBCX influenced the frequency of SCD crisis, emergency room visits, hospitalizations, and other sickle cell-related complications.Results:A total of 404 sessions of exchange transfusions were performed between November 2015 and August 2020 for 21 patients with SCD. The study included 9 adults (age ≥ 18 years) and 12 children with a median age of 12 years (2-31 years). During the study period, 3 adults left the program due to relocation out of state, patient's preference, or physician's decision. Table 1 summarizes the population demographic. The most common indication for enrollment in the RBCX program was recurrent sickle cell crisis (Figure 1). The mean number of emergency room visits before enrollment in the RBCX program was 22.5 visits (2-62 visits), which reduced after enrollment to 10.4 visits (0-65 visits), with a difference in mean of 12.1 visits (P=0.0021). The mean number of hospital admissions before enrollment in the RBCX program was 13.2 admissions(0-54 admissions), which also reduced to 6.7 admissions (0-50 admissions), with a significant difference in the means equal to 6. 6 admissions (P=0.0013) (Figure 2). Thirteen patients had a baseline ferritin > 500 ng/ml at enrollment; all of them had a decrease in their baseline ferritin during the study, with 4 of them achieving a new baseline < 500 ng/ml. Six patients had pre-existing antibodies at enrollment due to prior alloimmunization; however, no new alloantibodies were noticed after enrollment. The patients without preexisting antibodies were transfused with Rh and Kell matched blood. The patients with pre-existing antibodies were transfused with phenotypically matched blood. Three patients became pregnant during the study period, and their pregnancies were uncomplicated except for one patient with preeclampsia resulting in early delivery. There was no reportable death, acute chest syndrome, or stroke among the patients during the study period.ConclusionOutpatient chronic RBCX demonstrated safety and feasibility in both adults and children. It also showed promising outcomes in terms of reduction of sickle cell complications, number of emergency room visits and hospitalizations. These results can provide the basis for evaluating RBCX in a prospective study to better understand changes in quality of life and clinical outcomes of patients with SCD and limited therapeutic options. [Display omitted] DisclosuresGundabolu: Pfizer: Research Funding; Samus Therapeutics: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy.

Sickle cell crisis: how to spot the signs and reduce the risk

Sickle cell crisis: how to spot the signs and reduce the risk

Myocardial Performance Index Among Patients of Sickle Cell Disorder in Rural Teaching Hospital: A Case-Control Study.

Objective: To evaluate the myocardial performance index (MPI) in sickle cell disease (SCD) patients, and to compare MPI in healthy individuals.Methods: In this case-controlled study, patients of SCD and age- and sex-matched controls were included. MPI was determined using echocardiographic Doppler-derived parameters. MPI according to disease type, sickle cell crisis, and in the presence of co-morbidities was compared. Results: Between October 2018 and September 2020, we enrolled 100 SCD patients and 100 age and sex-matched controls. The MPI was significantly higher in SCD than in the control group (0.411±0.028 vs. 0.387±0.015, respectively; p<0.0001). There was no difference in MPI according to disease type as SS or AS (p=0.903). In patients with sickle cell crisis, mean MPI was significantly higher than those without sickle cell crisis (0.443±0.003 vs. 0.403±0.025, respectively; p<0.0001). In patients with comorbidities, mean MPI was significantly higher than those without any comorbidity (0.432±0.021 vs. 0.404±0.026, respectively; p<0.0001).Conclusion: MPI can be a non-invasive tool for assessing subclinical cardiac dysfunction and should be considered for evaluating patients with SCD.

SCREENING OF FUNGI FOR PRODUCTION AND PURIFICATION OF OMEGA-3 FATTYACID

Sickle cell hemoglobinopathy patients are vexed with sickle cell crises crises all through their life. Occurrence of jaundice in these patients is quite common and when present gets ascribed to the sickle cell crisis, sickle cell hepatopathy, intrahepatic cholestasis or cholelithisis. Further, incidence of viral hepatitis is extremely common in these patients. Clinically it is difficult to distinguish this aetiology. We have attempted to identify the criteria to help differentiate amongst sicklers which patients should be investigated for viral hepatitis. Also, sicklers with hepatitis have been studied against non sicklers with hepatitis and also complications of hepatitis in these two groups.

“False-positive” Myocardial Perfusion Scan in a patient presenting with sickle cell crisis

“False-positive” Myocardial Perfusion Scan in a patient presenting with sickle cell crisis

LONG-TERM SAFETY AND EFFICACY OF DEFERIPRONE FOR THE TREATMENT OF CHRONICALLY TRANSFUSED, IRON-OVERLOADED PATIENTS WITH SICKLE CELL DISEASE OR OTHER ANEMIAS

Assess the safety and efficacy of deferiprone (DFP) in chronically transfused, iron-overloaded patients with sickle cell disease (SCD) or other anemias. FIRST was a multicenter, 1-year, noninferiority trial of DFP vs deferoxamine (DFO). Patients ≥2 years of age were randomly assigned 2:1 to receive DFP or DFO. Those who completed FIRST could enter FIRST-EXT, a 2-year extension in which all patients received DFP. Thus, the baseline was the start of FIRST for patients randomized to DFP (up to 3 years for the DFP-DFP group), and the start of FIRST-EXT for patients randomized to DFO in FIRST (up to 2 years for the DFO- DFP group). In both studies, efficacy endpoints were yearly changes from baseline in liver iron concentration (LIC), cardiac MRI T2*, and serum ferritin (SF) level. All adverse drug reactions (ADRs) for both studies were recorded. In FIRST, patients (N = 228) were 46.9% female, mean age was 16.9 (standard deviation [SD] 9.6; range 3–59) years, 84.2% had SCD and 15.8% had other anemias. At 1 year, there were no significant (p > 0.05) differences in change in LIC, cardiac MRI T2*, or SF measures between the DFP and DFO intent-to-treat groups. Common ADRs (≥5% of patients) in the DFP group were abdominal pain, vomiting, pyrexia, increased alanine transaminase, increased aspartate aminotransferase, neutropenia, nausea, and chromaturia; in the DFO group, they were pyrexia and injection site pain. Serious ADRs in the DFP group were neutropenia (2.6%), increased transaminases (1.3%), and agranulocytosis, sickle cell crisis, epididymitis, Propionibacterium infection, bacterial sinusitis (infections not associated with neutropenia), vascular device infection, and migraine (0.7% each); in the DFO group, they were abdominal pain, arthritis, and headache (1.3% each). 134 Patients continued to FIRST-EXT (n = 89 DFP-DFP; n = 45 DFO-DFP): 60.4% were male, mean age was 16.2 (SD 8.6; range 4–47) years, 85.8% had SCD and 14.2% had other anemias. At baseline, all patients had elevated LIC with a mean (SD) of 14.93 (7.61) mg/g dry weight (dw), all had normal cardiac iron with a mean (SD) MRI T2* of 32.69 (17.66) ms, and all but 1 had elevated SF with a mean (SD) of 3894 (2591) μg/L. LIC decreased with mean (SD) reductions of -2.64 (4.64), -3.91 (6.38), and -6.64 (7.72) mg/g dw after 1, 2, and 3 years, respectively (p < 0.01 for all years). Cardiac iron remains in the normal range for all patients. SF levels declined with mean (SD) changes from baseline to years 1, 2, and 3 of -1 (1986), -771 (2171), and -1016 (3617) μg/L, respectively (p < 0.05 for years 2 and 3). No new ADRs (observed in 30.6% of patients) were reported. One patient withdrew due to ADRs of thrombocytopenia and neutropenia, which resolved. Another patient withdrew due to generalized edema and died for reasons unknown 17 days after withdrawal from the study. DFP effectively controlled iron burden in chronically transfused patients with SCD and other anemias, and it was noninferior to DFO. DFP use was associated with reductions in LIC and SF levels. Cardiac MRI T2* remained normal. DFP was well tolerated in patients who received up to 3 years of treatment, with no new safety concerns. We thank Dr. M Badr, Dr. B Inusa, Dr. AAM Adly, Dr. Y Kilinc, C Fradette, and NT Temin for their contribution to the studies. Sponsored by Chiesi Global Rare Diseases; medical writing support provided by Oxford PharmaGenesis Inc., and funded by Chiesi.

S2741 Sickling Manifestations: A Challenging Case of Sickle Cell Hepatopathy

Introduction: Sickle cell hepatopathy (SCH) is an entity describing a pattern of liver injury seen in an estimated ∼10% of patients with sickle cell disease (SCD). It is more prevalent in the Sub-Saharan African region and South-East Asia. This entity is classified according to its clinical presentation into acute and chronic which differs in clinical diagnosis and management. Case Description/Methods: A 51-year-old African American male with SCD presented to our ER with complaint of joint pain and shortness of breath. Patient-reported progressive bilateral lower extremity arthralgia, sharp, 8/10 in severity for 1 week. Reported Dyspnea on exertion. Recurrent sickle cell crises were noted. The patient recently discontinued hydroxyurea because of non-healing cutaneous ulcerations. Vitals marked hypoxia at 87%, otherwise stable. Physical examination revealed icteric sclerae with bilateral lung crackles prominent at the bases. Labs showed hemoglobin at 3.0 g/dl, HB S 28.7% with reticulocyte count at 17.41%. Chemistry panel showed alkaline phosphatase (ALP) at 209 U/L, Total bilirubin at 7.0 mg/dl with direct bilirubin at 4.7 mg/dl. Gamma-glutamyl transpeptidase (GGT) was normal. Chest Xray showed bilateral multifocal infiltrates. Abdominal ultrasound was unremarkable. Computed tomography of the chest showed interspersed ground-glass opacities. Hepatology was consulted for assessment of elevated ALP and Total bilirubin. Clinical suspicion was (SCH). Patient was given multiple blood transfusions. The need for liver transplant (LT) was investigated and deemed not necessary. Pathology was reviewed. Discussion: (SCH) is included in the differential of liver injury, therefore, identifying this entity from other causes of liver disease is important. It is more prevalent in the US now. Hence, an urgent need to find new treatment options in addition to emergent blood transfusion and LT is required. Iron quantification and determining need for chelation therapy is crucial and affects long-term outcomes. LT in SCD patients is controversial due to high risk of post-transplant complications. More studies and international registries are needed to expand our knowledge of the benefits and risks of LT in patients with SCD. We anticipate that (SCH) will become a burden on the health care system in the aging population of SCD patients as they will require more blood transfusions. With a current national shortage supply, we fear future complications will include an increase in mortality rates within this patient population.Figure 1.: a (H&E stain 400x) showing sickled RBC in the sinusoids. b (H&E stain 40x) The lobules show marked sinusoidal dilatation and congestion with elongated RBCs, more pronounced in zone 3 with extravasated RBCs. c (Trichrome stain 200x) Trichrome stain shows diffuse sinusoidal fibrosis, portal, periportal with bridging.

Ketamine administration for acute painful sickle cell crisis: Arandomized controlled trial.

ObjectiveThe objective was to evaluate the efficacy and safety of single‐dose ketamine infusion in adults with sickle cell disease (SCD) who presented with acute sickle vasoocclusive crisis (VOC).MethodsThis study was a parallel‐group, prospective, randomized, double‐blind, pragmatic trial. Participants were randomized to receive a single dose of either ketamine or morphine, infused over 30 min. Primary outcome was mean difference in the numerical pain rating scale (NPRS) score over 2 h. NPRS was recorded every 30 min for a maximum of 180 min and secondary outcomes were cumulative dose of opioids, emergency department (ED) length of stay, hospital admission, change in vital signs, and drug‐related side effects. Authors performed the analysis using intention‐to‐treat principle.ResultA total of 278 adults with SCD and who presented with acute sickle VOC participated in this trial. A total of 138 were allocated to the ketamine group. Mean (±standard deviation [SD]) NPRS scores over 2 h were 5.7 (±2.13) and 5.6 (±1.90) in the ketamine and morphine groups. The ketamine group received significantly lower cumulative doses of morphine during their ED stay (mean ± SD = 4.5 ± 4.6 mg) than of the morphine group (mean ± SD = 8.5 ± 7.55 mg). Both groups had similar rates of hospital admission: 6.3% in the ketamine group had drug‐related side effects compared to 2.2% in the morphine group.ConclusionEarly use of ketamine in adults with VOC resulted in a meaningful reduction in pain scores over a 2‐h period and reduced the cumulative morphine dose in the ED with no significant drug‐related side effects in the ketamine‐treated group.

Utilization of Patient-Controlled Analgesia Reduces Length of Stay of Sickle Cell Crisis Hospitalizations.

Sickle cell crisis hospitalizations are emotionally and financially burdensome to patients and healthcare systems, and processes to decrease the frequency or length of stay of these crises should be examined. This is a multicenter retrospective hospital record review of sickle cell crisis hospitalizations as defined by ICD-10 codes (D57.1-4), from January 2016 through December 2019, examining inpatient medication administration records and length of stay among admitted adults aged 18-65 years. Patient controlled analgesia orders using morphine, hydromorphone, fentanyl and/or merperidine at any point of an admission (n=188) were compared to admissions without any patient-controlled analgesia orders (n=2,159). The primary end point was hospital length of stay in days. A secondary analysis examining patients with or without greater than four admissions was also conducted. The 1,675 patients who met criteria comprised 2,347 sickle cell hospitalizations during the four years examined. Of those admissions, 188 had at least one patient-controlled analgesic documented in their chart and had an average length of stay of 4.54 days (SD 3.34). The 2,159 admissions without any patient-controlled analgesia had an average length of stay of 5.74 days (SD 4.64). The difference of 1.2 days between the groups was statistically significant (p≤0.0001) using a Wilcoxon signed-rank test. Among patients with sickle cell crises who required inpatient hospitalizations, the use of patient-controlled analgesia demonstrated a statistically significant reduction of 1.2 days in their total length of stay. These findings support potentially changing hospital protocols to increase patient-controlled analgesia utilization.

Awareness is key when treating sickle cell crisis in acute settings

Awareness is key when treating sickle cell crisis in acute settings