DEVELOPMENT OF A HYDROXYCARBAMIDE TELEPHONE CLINIC FOR CHILDREN WITH SICKLE CELL DISEASE

Aim Develop the hydroxycarbamide prescribing process for sickle cell disease to improve outcomes and patient experience through: implementing electronic prescribing;identifying and addressing non-adherence;optimising doses;improving accessibility of medication and developing a hydroxycarbamide telephone clinic. Method The clinic was planned to be piloted mid-2020 however due to the COVID pandemic requiring more services to be delivered remotely the timeline was accelerated and all patients switched to telephone reviews in March 2020. New patients are commenced on hydroxycarbamide at a face-to-face outpatient appointment which includes counselling and consent, review of baseline bloods, introduction to the telephone clinic and medication counselling. Patients are then eligible for the hydroxycarbamide telephone clinic. Patients attend outpatient phlebotomy for the necessary monitoring blood tests prior to their telephone appointment. At the telephone appointment a virtual review takes place including a review of symptoms, blood results, medication adherence and adverse effects. An 8-12 week supply of hydroxycarbamide is prescribed by a nurse or pharmacist prescriber and sent to the patient's local pharmacy or home address by the hospital outsourced pharmacy. Follow up appointments are made every 8-12 weeks. Patients continue to have face to face medical appointments;the interval is determined by individual patient factors but a minimum of annually. Results In September 2019 (prior to electronic prescribing) an audit of patients who had been on hydroxycarbamide for 9 months or more (n=26) had a mean dose of 21.7mg/kg. A repeat audit in July 2021 showed a mean dose of 26.9mg/kg (n=36). Electronic prescribing has facilitated more accurate prescription records and structured dose escalation. It also supports better monitoring of adherence since it is clear during a review when the next supply should be required. This along with questioning what medication supply patients have at home allows adherence issues to be identified and discussed with patients/carers. An audit of haematology outpatient clinic waiting times prior to implementation showed an average wait time of 82 minutes;one of the recommendations was to implement this telephone clinic. In a patient/carer survey on care during the pandemic, 88% of respondents were happy with the telephone reviews they had received and 82% wished to continue with telephone clinics. Conclusion The results show an escalation in hydroxycarbamide dose which correlates with a higher fetal haemoglobin, this in turn is associated with increased survival.1. This has been facilitated by the increased opportunity to focus on prescribing and medication review. From March 2020 to May 2021, due to the pandemic, dose escalation only took place if patients were admitted with crisis so further improvement may be seen in the future.

COVID-19 Infection and Outcomes at a Comprehensive Sickle Cell Center

Introduction: The Grady Comprehensive Sickle Cell (SC) center is the largest adult sickle cell center in the United States (US) and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). In 2019, the center provided 3077 sickle cell outpatient visits and 3695 acute care visits. When the COVID-19 pandemic reached the US, the center had a precipitous drop in the number of both outpatient clinic and acute care visits as state regulations for lockdown were passed. This report follows all the COVID-19 cases at a single adult center for sickle cell disease in one year. Methods: The clinical database has been tracking COVID-19 cases reported. Out of a total of 1343 patients, 55 patients contracted COVID-19 and were tracked in the clinical database with IRB approval. Results: Of the 55 patients with COVID-19, 28 were female and 27 were male. By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ+ thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain (defined as patients experiencing daily pain episodes for more than 4 days a week for the last 3 months) and calculation of daily morphine equivalents were reported in clinic follow-up and the narcotic database utilization. 47% of the patients had chronic pain and the median morphine equivalents was 90 mg daily (45-225mg). The rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19 was 80%. 49% of the SC patients' visits were related to VOE and 27% related to COVID-19 primarily. 20% of SC patients with COVID-19 were not seen in any emergency setting or required any hospitalization. The COVID-19 signs and symptoms experienced by the patients were as follows: 58% had pain as the main presenting symptom, followed by cough and fever (40%), dyspnea (31%), and pneumonia with chest x-ray evidence (25%). 2 patients developed acute respiratory distress syndrome (ARDS) and were intubated, and 2 patients died. 29% of the patients had lung findings on imaging and 16 of 55 patients required treatment with the use of Remdesivir in 9, dexamethasone in 8 and red cell products in 7 of the 16 patients. The 2 patients who died had both presented with COVID-19 infection in June and July 2020 respectively. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure for which a red cell erythrocytapheresis was attempted. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma with development of multi-organ failure and ARDS. Discussion: Several reports were published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 16 out of 55 patients who had contracted COVID-19 required treatment and 2 of those 16 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 when 20 total cases were diagnosed (from March to Septemeber 2020). The remaining 35 cases registered zero deaths (October 2020 to March 2021) with the rate of complicated COVID-19 hospitalizations decreasing with better treatment available. In addition, the timeline for the COVID-19 cases reported fits the population timeline of 2 peaks respectively happening in the summer of 2020 and the Winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the center adopted virtual visits to deliver healthcare needs. This measure has aided in protecting patients against COVID-19. Additionally, it is interesting that despite the seco d peak in the winter of 2021, there were no reported deaths among the patients who developed COVID-19. This finding can suggest that despite the concern for morbidity and mortality of sickle cell patients, their diligence and awareness to stay home during the pandemic has proven crucial in reducing morbidity and mortality and the option of virtual visits for healthcare delivery was key and should be utilized further in sickle cell care. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Acquired Aplastic Anemia in Immunocompetent Pediatric Patients with Asymptomatic COVID-19 Infection: A Case Series

Background: In pediatrics, acquired aplastic anemia (AA) is most commonly due to infection, particularly viruses, when a cause can be identified. Coronavirus disease 2019 (COVID-19) has affected more than 197 million people worldwide, and children typically experience a less severe disease course. COVID-19 is known to cause transient hematologic abnormalities, including leukopenia, lymphopenia, anemia and thrombocytosis or thrombocytopenia in severe cases. Objectives: Describe three cases of COVID-19 associated acquired aplastic anemia in immunocompetent pediatric patients. Design/Methods: Case series established by retrospective review of the electronic medical record. Results: Case 1: An 8-year-old Hispanic male presented with a three-week history of increased bruising and a one-week history of progressive exercise intolerance, shortness of breath, pallor and fatigue. Labs showed pancytopenia. Bone marrow aspirate and biopsy was markedly hypocellular at 5-10% consistent with aplastic anemia (Figure 1). Work-up for the etiology of his aplastic anemia was only significant for positive SARS-COV-2 antibodies and a SEC23B variant of unknown significance on a comprehensive bone marrow failure (BMF)/myelodysplastic syndrome (MDS)/leukemia panel from the Children's Hospital of Philadelphia (CHOP). He was treated with eltrombopag olamine and then proceeded to immunotherapy with cyclosporine (CsA) and horse antithymocyte globulin (ATG) when a sibling match was not identified for hematopoietic stem cell transplant (HSCT). Three months later, his peripheral blood counts have improved, and he is no longer transfusion-dependent. Repeat bone marrow aspirate and biopsy continues to show markedly hypocellularity at <5%. Case 2: A 5-year-old non-Hispanic white female presented with a two-week history of easy bruising, petechial rash, fatigue and bone pain. Labs showed pancytopenia, and bone marrow aspirate and biopsy showed marked hypocellularity at 5-10% consistent with aplastic anemia (Figure 2). Her aplastic anemia work-up was significant for positive SARS-COV-2 antibodies and subclinical RBC and WBC paroxysmal nocturnal hemoglobinuria (PNH) clones. She was started on eltrombopag olamine and then proceeded to immunotherapy with CsA and ATG when a matched sibling donor was not identified. Three months later, she continues to be severely neutropenic, anemic and thrombocytopenic requiring multiple transfusions. Repeat bone marrow aspirate and biopsy showed variable cellularity with some areas 10-20% and others 70% with an overall cellularity of 50%. Case 3: An 8-year-old non-Hispanic white female presented with a 10-day history of fatigue, bilateral leg pain and pallor. Labs showed pancytopenia, elevated inflammatory markers and elevated hemoglobin F. Bone marrow aspirate and biopsy demonstrated mild-moderate hypocellularity at 40-50%, left-shifted myelopoiesis and dyspoiesis in the erythroid and megakaryocytic cell lines (Figure 3). MDS and acute lymphoblastic leukemia (ALL) fluorescence in situ hybridization (FISH) panels were negative. Additional work-up revealed positive SARS-COV-2 antibodies. Her pancytopenia resolved within two weeks of her initial hospitalization. Four months later, she presented with increased bruising and fatigue. Labs showed leukocytosis, thrombocytopenia, anemia and circulating peripheral blasts. Bone marrow aspirate and biopsy was consistent with B-cell ALL. She is receiving chemotherapy on study COG AALL1732. Conclusion: Severe aplastic anemia (SAA) has high morbidity and mortality, and timely diagnosis is needed for appropriate treatment. Multiple different viral infections have been known to cause acquired aplastic anemia. Data on all the sequelae of COVID-19 infection is still emerging, but it is plausible that COVID-19 infection may cause SAA. All three patients were found to have positive COVID-19 antibodies but did not have any evidence of previous COVID-19 infection. Further research and follow-up is needed to determine if previous COVID-19 infection is indeed a risk factor for development of S A. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Sickle Cell Disease and COVID-19 Infection: A Single-Center Experience

Background and Objectives: The COVID-19 (CO19) pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics, and society. Several reports have shown that African Americans (AA) have been disproportionately affected by the CO19 pandemic. Limited data have suggested that sickle cell disease (SCD) could be one of the several reasons for higher morbidity and mortality related to CO19 among AA. Recent reports have suggested higher-than-average morbidity and mortality related to CO19 among patients with SCD. We conducted a retrospective, single-institution study in adult patients with SCD who were diagnosed with CO19 infection and their outcomes. Methods: After IRB approval, we conducted a chart review of adult patients (greater than 18 years) with SCD who were diagnosed with CO19 infection between March 1st, 2020, and March 31st, 2021. We recorded demographic data including age, gender, social factors (the type of insurance, availability of primary care provider (PCP), living alone/not), clinical parameters (type of SCD, co-morbidities), outpatient management of SCD, and how CO19 infection was managed like inpatient admission and complications. In patients who were admitted or seen in the emergency department (ED), we collected additional data including vitals, labs, the severity of illness, complications, length of stay, and outcomes. Computations were performed using statistical software SAS 9.4 for Windows. Results: We found a total of 51 patients with SCD diagnosed with CO19 infection in the above period. The median age of patients was 30 years. 61% were females and 39 % were males. All of them were AA. 11.76% were living alone, 49.02% were living with family, 1.96% (1 patient) was institutionalized, and the living situation was unknown in 37.25%. Most of the patients had Medicaid Insurance (52.94%), Medicare in 33.3%, private insurance in 13.73 % and 2% were uninsured. Only 64.71% of patients had a PCP. 60% had HbSS disease, 32% had HbSC disease, 4% had HbS-beta thalassemia, one patient each had HbSS with hereditary persistence of HbF and HbS/HbD. Comorbidities and previous history included acute chest syndrome in 65.96%, avascular necrosis in 36.96%, leg ulcers in 8.7%, hypertension in 8.7%, sickle cell retinopathy in 14.57%, cerebrovascular disease in 26.19%, chronic kidney disease in 7.69%, venous thromboembolism (VTE) in 20.41%, 10.41% were on anticoagulation, history of HIV and hepatitis C infection in 6.38%. 28.21% of patients were maintained on partial exchange transfusions as an outpatient for various indications. 72.73% were on hydroxyurea, 7.5% were on crizanlizumab, 5.26% were on voxelotor and 26.83% were on iron chelation. Vitals and pertinent lab values on initial assessment were recorded and many patients had missing data. On presentation, 25.53% were febrile, 29.17% of patients were tachycardic, 31.25% were hypoxic (SpO2 < 95%), 38.46% were tachypneic, 59.18% had a body mass index (BMI) of > 24.9. Median hemoglobin and hematocrit were 8.9/27.4 g/dL. The median white blood cell count was 9490/uL and platelets were 315,000/uL. Median ferritin was 1573 ug/L. Median bilirubin and creatinine were 2.05 mg/dL and 0.86 mg/dL. The patients were further stratified based on the clinical location where CO19 infection was managed (Table 1). 39.3% were diagnosed in the outpatient setting/ED and 60.3% in the inpatient setting. Among 51 patients, 5.71% (n=2) required ICU admission and was mechanically ventilated. 17.5% received dexamethasone, 7.69% received remdesivir, 2.76% received convalescent plasma, 17.07% had infections and 47% received antibiotics. Only one patient received an exchange transfusion during admission. One patient developed a new VTE after CO19 infection. On statistical analysis, the only factor which impacted the clinical location of management was tachycardia (P=0.007). Of the 51 patients, only 3.9% (2 patients) died of complications of CO19 infection, one with hypoxic respiratory failure, disseminated intravascular coagulation, shock, and the other one with pulmonary mbolism. 13% were readmitted within a month, one of them was admitted with a new pulmonary embolism and the others were admitted for acute painful episodes. Conclusion: We found a mortality rate of 3.9% in our single-center study of patients with SCD and CO19 infection. This mortality rate is lower than other published experiences in patients with SCD and CO19 infection. [Formula presented] Disclosures: Master: Blue Bird Bio: Current holder of individual stocks in a privately-held company.