Health Care Utilization for Painful Events Is Associated with Early Mortality in a Contemporary Population of Adults with Sickle Cell Anemia

Abstract Abstract 2115 Background: Painful vaso-occlusive crises are the most common symptom associated with sickle cell anemia (SCA) and show a large inter-patient variability in the frequency and severity. Historically a high rate of admissions for pain is associated with early mortality in SCA adults. Modern day management of SCA includes screening for life threatening complications such as pulmonary hypertension and disease modifying therapies such as hydroxyurea and chronic blood transfusions. It has also become clear that all acute painful events including some self reported crisis do not lead to ED visit/ hospitalization therefore use of healthcare utilization may underestimate the actual frequency of painful vaso-occlusive crises. The present study determined if ED visit/ hospitalizations for painful vaso-occlusive crises remain a marker of early mortality in the modern era. Methods: To determine the relative contribution of pain and other established risk factors for death in a contemporary adult cohort with sickle cell anemia, we analyzed data of SCA individuals who were evaluated at NIH between February 2001 and June 2007 for screening of the IRB approved protocol to study pulmonary hypertension in sickle cell disease. Self reported history of vaso-occlusive painful events requiring visit to an emergency department (ED) or in-patient hospitalization in 12 months preceding the enrollment was used to stratify study subjects into no-ED visit/ hospitalization or ED visit/hospitalization group. Characteristics between the groups were compared. Doppler echocardiography was used to estimate systolic pulmonary artery pressure through measurement of the tricuspid regurgitation velocity (TRV). Study subjects were followed prospectively and age at death was recorded. Results: One hundred and four (40%) SCA subjects reported no ED visit/ hospitalization while 160 (60%) reported at least one ED visit/ hospitalization in 12 months preceding the enrollment. Although not statistically significant, a higher proportion of study participants in the ED visit/ hospitalization group were on hydroxyurea (38 vs. 69%; P=0.4), and more likely to have received > 10 red cell transfusions (37 vs. 48%; P= 0.09). The no-ED/ hospitalization group and ED/ hospitalization groups were not different in median age (33 vs. 31; P=0.1) or fetal hemoglobin concentration (7.7 vs. 6.9%; P=0.3). Overall forty (15.1%) individuals died during the median follow-up period of 5 years. Cox proportional hazards analysis was performed to determine if severe pain crisis requiring ED visits/hospitalizations were associated with early mortality after adjusting for other known risk factors for mortality (Table 1). Risk for mortality was significantly associated with a history of severe pain crisis requiring ED visit/hospitalization in preceding year (RR 2.81, 95% CI: 1.2–6.4, P= 0.04), elevated TRV ≥ 3 m/s (RR 4.07, 95% CI: 1.3–12.8, P= 0.02) and elevated ferritin (RR 2.31, 95% CI: 1.0–5.0, P= 0.04). Conclusions: Severe painful episodes requiring health care utilization are associated with premature mortality and despite likely underestimation of actual frequency of pain, remain a marker of disease severity. Elevated TRV a marker of elevated pulmonary arterial pressure and early mortality has a cumulative effect with pain on reduced survival. Consistent with Cooperative Study of Sickle Cell Disease (CSSCD) report, higher hemoglobin (and lower LDH) was associated with reports of ED visit/ hospitalization likely related to increased viscosity. We conclude that as a group, SCA patients reporting severe pain requiring ED visits /hospitalization and elevated TRV are at the highest risk for shortened survival. Disclosures: No relevant conflicts of interest to declare.

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Epidemiology and Risk Factors for Pain In Children and Adolescent with Sickle Cell Anemia.

Blood ◽

10.1182/blood.v116.21.1651.1651 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1651-1651 ◽

Cited By ~ 1

Author(s):

Deepika Darbari ◽

Onyinye Onyekwere ◽

Mehdi Nouraie ◽

Gregory J. Kato ◽

Caterina Minniti ◽

...

Keyword(s):

Risk Factors ◽

Confidence Interval ◽

Children And Adolescents ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Odds Ratio ◽

Severe Pain ◽

History Of ◽

Pain Crisis ◽

Thalassemia Trait

Abstract Abstract 1651 Background: Pain crises are the most common symptom experienced by individuals with sickle cell anemia (SCA). Frequency of pain crises varies significantly and high rate is a risk factor for higher mortality in adults with SCA. The risk factors for pain crises in children and adolescents with SCA are not completely understood. To determine factors associated with frequent severe pain crises, we analyzed the cohort of children and adolescents with SCA who were enrolled in the prospective study “The Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH)”. All children were evaluated in their steady, non-crisis state. Methods: Family-reported history of number of severe pain crises in the preceding 12 months was recorded prospectively in 365 children and adolescents with SCA. Severe pain crises were defined as painful vaso-occlusive episodes requiring evaluation in Emergency Department (ED) or in-patient hospitalization. Lifetime history of red cell transfusions, echocardiography, and laboratory studies were obtained. Clinical and laboratory characteristics of study subjects who had ≥3 severe pain crises in the preceding year were compared to subjects with < 3 severe pain crises. Results: Study subject ranged in age from 3–20 years and 175 (48%) were female. Seventy two children (20 %) had ≥3 severe pain crises in the preceding year (frequent pain crisis group); 293 (80%) children had < 3 severe pain crises (infrequent pain crisis group), including 224 (61%) subjects who had no admissions/ ED visits for pain. Associated factors for frequent pain crisis included older age (odds ratio 1.2; 95% confidence interval 1.12–1.35; P <0.001) and α-thalassemia trait (odds ratio 3.22; 95% confidence interval 1.55–6.69; P =0.002) while higher steady state serum lactate dehydrogenase (LDH) was associated with infrequent pain crisis (odds ratio 0.35; 95% confidence interval 0.13–0.98; P =0.045). In a group of patients without α-thalassemia trait, older age and low LDH were linked to frequent pain crisis. Subjects in the frequent pain crisis group had higher median hemoglobin (9.0 vs. 8.5 gm/dL; p=0.003) and higher ferritin (median 455 vs. 191 ng/mL; p=0.008). Higher ferritin in the frequent pain crisis group was mirrored by the higher percentage who reported >10 lifetime transfusions (42% vs. 22%; p=0.001). Median tricuspid regurgitation jet velocity (TRV) was higher in the frequent pain crisis group (2.41 vs. 2.31; p= 0.001) but the proportion of children with TRV>2.5 was not different (19.4% vs.11.5% in infrequent crises group; p=0.09). Hydroxyurea use was not different between the groups (51% vs. 40%; p=0.08) nor was fetal hemoglobin (10% vs. 12%; p=0.2). Conclusions: The occurrence of severe pain crisis varies among children and adolescents with SCA with a large number of children experiencing no severe painful episodes. Consistent with the Cooperative Study of Sickle Cell Disease report, the risk of severe pain crisis increases with age. Individuals with α-thalassemia trait are likely to experience more frequent pain crises possibly related to higher hemoglobin concentration and viscosity. However, even after controlling for α-thalassemia trait, children and adolescents who reported more frequent severe pain crises showed evidence of less hemolysis, consistent with a hypothetical model associating the hemolytic subphenotype of SCA with less frequent vasoocclusive pain crises. Further studies are indicated to identify the molecular mechanisms of pain in sickle cell anemia. Disclosures: No relevant conflicts of interest to declare.

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Patients with Sickle Cell Disease and Venous Thromboembolism Experience Increased Frequency of Vasoocclusive Events

Blood ◽

10.1182/blood-2019-122199 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 999-999

Author(s):

Romy Carmen Lawrence ◽

Sarah L Khan ◽

Vishal Gupta ◽

Brittany Scarpato ◽

Rachel Strykowski ◽

...

Keyword(s):

Venous Thromboembolism ◽

Sickle Cell Disease ◽

Acute Care ◽

Sickle Cell ◽

Hospital Admissions ◽

Care Utilization ◽

Cell Disease ◽

History Of ◽

Acute Care Utilization ◽

Ed Visits

Introduction Patients with sickle cell disease (SCD) are at increased risk for venous thromboembolism (VTE). By age 40, 11-12% of SCD patients have experienced a VTE. VTE confers nearly a three-fold increase in mortality risk for individuals with SCD. We hypothesized that VTE increases subsequent SCD severity which may increase acute care utilization. We investigated the association between VTE and rates of vaso-occlusive events (VOE) and acute care utilization for individuals with SCD. Methods We performed a retrospective longitudinal chart review of 239 adults with SCD who received care at our institution between 2003 and 2018. VTE was defined as deep venous thrombosis (DVT) diagnosed by Duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. Medical histories, laboratories and medication use for all subjects were obtained. For VTE patients, clinical data for 1- and 5- years post-VTE were obtained and compared to 1 year prior to the VTE. For non-VTE patients, data were obtained at baseline and compared to five years later. We evaluated all acute care visits for the presence of a SCD-related problem, specifically assessing if a VOE or acute chest syndrome (ACS) occurred. We calculated rates of VOE, ACS, Emergency Department (ED) visits and hospitalizations prior to and subsequent to a VTE and compared these to occurrence rates among those without VTE. Data were analyzed using Stata 14.2. Results In our cohort of 239 individuals with SCD, 153 (64%) were HbSS/HbSβ0 and 127(53%) were female. Fifty-six individuals (23%) had a history of VTE; 20 had a DVT (36%), 33 had a PE (59%), and 3 had both (5%). Patients with VTE had a higher frequency of prior history of ACS (p<0.001), stroke (p=0.013), splenectomy (p=0.033), and avascular necrosis (p<0.001) than those without a VTE. Prior to their VTE, these patients had higher white blood cell (11.8 x103 [9-15 x 103] vs 9.7 x103 [7-12 x 103], p=0.047) and platelet counts (378 x 103 [272-485 x 103] vs 322 x 103 [244-400 x 103], p=0.007) than those without a VTE. During five years of follow-up after a VTE, these patients had 6.32 (SD 14.97) ED visits per year compared to 2.84 (SD 5.93, p<0.03) ED visits per year in those without a VTE. Ninety two percent of these ED visits were SCD-related; 73% were for VOE and 4% for ACS. Additionally, SCD patients with a VTE had an increase in all-cause hospital admissions (2.84 [SD 3.26] vs 1.43 [SD 2.86], p=0.003) and SCD-related hospital admissions (2.61 [SD 3.13] vs 1.23 [SD 2.74], p=0.001) per year compared to those without VTE. Conclusion VTE is a frequent complication in patients with SCD. Our study suggests that patients who experience a VTE have greater SCD severity as evidenced by increased VOE, ED and hospital utilization. These data suggest that VTE is not merely an isolated event in SCD patients and that it may either serve as an indicator of disease severity or contribute to overall disease pathophysiology. Disclosures Sloan: Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy; Merck: Other: endpoint review commitee.

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Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies

PEDIATRICS ◽

10.1542/peds.83.5.813 ◽

1989 ◽

Vol 83 (5) ◽

pp. 813-814

Author(s):

DORIS WETHERS ◽

HOWARD PEARSON ◽

MARILYN GASTON

Keyword(s):

Sickle Cell Disease ◽

Early Diagnosis ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Case Fatality ◽

The United States ◽

Early Mortality ◽

Cell Disease ◽

Newborn Period ◽

The Past

Hemoglobinopathies represent one of the major health problems in the United States and constitute the most common genetic disorders in some populations. Sickle cell disease (SS, SC, S-β-thalassemia) alone affects about one in 400 American black newborns, as well as persons of African, Mediterranean, Asian, Caribbean, Middle Eastern, and South and Central American origins. For the past 20 years, the medical profession has known that children with sickle cell anemia have an increased susceptibility to severe bacterial infection, particularly due to Streptococcus pneumoniae. The risk of major infection and death posed by this organism is greatest in the first 3 years of life and can occur as early as 3 months of age. In fact, this infection may be the first clinical manifestation of disease. The infection can be fulminant, progressing from the onset of fever to death in a matter of hours, and the case fatality rate is reported as high as 30%. In addition, acute splenic sequestration, another acute catastrophic event, contributes to early mortality in children with sickle cell anemia and may occur as early as 5 months of age. It has been proposed that early diagnosis to identify infants with major sickle hemoglobinopathies, who have a high risk of early mortality and morbidity, is essential to institute appropriate ongoing care and effective measures of prophylaxis and intervention. Early diagnosis of hemoglobinopathies should be in the newborn period. Even though the technology to screen infants in the newborn period has been available for the past 15 to 20 years, screening has not received widespread acceptance.

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Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease

Therapeutic Advances in Hematology ◽

10.1177/2040620720955000 ◽

2020 ◽

Vol 11 ◽

pp. 204062072095500

Author(s):

Ifeyinwa Osunkwo ◽

Deepa Manwani ◽

Julie Kanter

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Severe Pain ◽

Management Strategies ◽

Organ Damage ◽

Care Utilization ◽

Cell Disease ◽

High Resource ◽

Emerging Treatments

Individuals with sickle cell disease (SCD) are living further into adulthood in high-resource countries. However, despite increased quantity of life, recurrent, acute painful episodes cause significant morbidity for affected individuals. These SCD-related painful episodes, also referred to as vaso-occlusive crises (VOCs), have multifactorial causes, and they often occur as a result of multicellular aggregation and vascular adherence of red blood cells, neutrophils, and platelets, leading to recurrent and unpredictable occlusion of the microcirculation. In addition to severe pain, long-term complications of vaso-occlusion may include damage to muscle and/or bone, in addition to vital organs such as the liver, spleen, kidneys, and brain. Severe pain associated with VOCs also has a substantial detrimental impact on quality of life for individuals with SCD, and is associated with increased health care utilization, financial hardship, and impairments in education and vocation attainment. Previous treatments have targeted primarily SCD symptom management, or were broad nontargeted therapies, and include oral or parenteral hydration, analgesics (including opioids), nonsteroidal anti-inflammatory agents, and various other types of nonpharmacologic pain management strategies to treat the pain associated with VOC. With increased understanding of the pathophysiology of VOCs, there are several new potential therapies that specifically target the pathologic process of vaso-occlusion. These new therapies may reduce cell adhesion and inflammation, leading to decreased incidence of VOCs and prevention of end-organ damage. In this review, we consider the benefits and limitations of current treatments to reduce the occurrence of VOCs in individuals with SCD and the potential impact of emerging treatments on future disease management.

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Predictors of Mortality in Children and Adolescents with Sickle Cell Disease: The PUSH Study

Blood ◽

10.1182/blood.v118.21.515.515 ◽

2011 ◽

Vol 118 (21) ◽

pp. 515-515 ◽

Cited By ~ 1

Author(s):

Mehdi Nouraie ◽

Sohail R. Rana ◽

Oswaldo L Castro ◽

Lori Luchtman-Jones ◽

Craig Sable ◽

...

Keyword(s):

Sickle Cell Disease ◽

Children And Adolescents ◽

Sickle Cell ◽

Severe Pain ◽

Blood Transfusions ◽

Cell Disease ◽

Risk Of Death ◽

The Past ◽

History Of

Abstract Abstract 515 Background: Recent studies indicate that the disease-specific mortality In sickle cell anemia is about 6% in children up to 18 years and 15% in the 18–30 year age group, yielding a cumulative mortality of 21% by age 30 years. It is important to identify children at high risk so that early interventions can be developed to reduce this high mortality. Methods: We prospectively enrolled 505 children and adolescents with sickle cell disease in 2005–2010, 380 with hemoglobin SS and 130 with other genotypes. The median age at enrollment was 12 years with a range of 3 to 20 years. Baseline clinical features, echocardiography, six-minute walk test and pulmonary function testing were performed at steady-state. Follow-up for mortality has been performed in 470 of the participants at a median of 37 months after enrollment, range of 1 to 59 months. Results: Six of 470 patients (1.3%) died during the follow-up period, five with hemoglobin SS and one with hemoglobin SC. The median age at the time of death in these six participants was 20 years, range of 15 to 23 years. Death occurred during the follow-up period in 2.7% of participants over 12 years of age at enrollment and 3.7% of those over 15 years of age. The causes of death were stroke in 4, multiorgan failure in 1 and unknown in 1. Death occurred in 5.9% of 51 participants with a history of stroke versus 0.7% of 416 without stroke history; in 3.5% of 113 participants with a history of asthma versus 0.6% of 354 without asthma history; in 4.9% of 103 participants with 10 or more blood transfusions lifetime versus 0.3% of 359 with less than 10 blood transfusions; in 3.3% of 90 participants with two or more severe pain episodes in the past year versus 0.8% of 380 participants with less than two severe pain episodes in the past year. In age-adjusted analyses, the hazards ratio (95% CI) of death was 6.1 (1.2-30.5) for history of stroke (P=0.029), 10.2 (1.2-89.5) for history of frequent blood transfusions (P=0.036), 5.8 (1.1-31.8) for history of asthma (P=0.044) and 1.07 (1.00-1.14) for frequent severe pain episodes (P=0.047). Clinical findings associated with these risk factors included higher concentrations of markers of hemolysis for history of stroke and history of frequent blood transfusions, decreased FEV1/FVC and increased total lung capacity for history of asthma, and lower concentrations of markers of hemolysis and high ECHO-determined tricuspid regurgitation velocity for history of frequent severe pain episodes. Conclusions: Over a median of three years of observation of this cohort, no deaths occurred among 248 sickle cell disease children 12 years of age or younger at enrollment but there were 6 deaths among 222 participants 13–20 years of age at enrollment. In bi-variate age-adjusted analyses, histories of stroke, asthma, frequent blood transfusions and frequent pain episodes were associated with an increased risk of death. Strikingly, four of the five deaths in which the cause was known were due to stroke. The present data on mortality in the PUSH study suggest that prevention of stroke is critical in improving the survival in adolescents and young adults with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

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Evidence-Based Mini-Review: Are Systemic Corticosteroids an Effective Treatment for Acute Pain in Sickle Cell Disease?

Hematology ◽

10.1182/asheducation-2010.1.416 ◽

2010 ◽

Vol 2010 (1) ◽

pp. 416-417 ◽

Cited By ~ 5

Author(s):

L. Vandy Black ◽

Wally R. Smith

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Adjunctive Treatment ◽

Cell Disease ◽

X Ray ◽

Systemic Corticosteroids ◽

Potential Efficacy ◽

History Of ◽

Chest X Ray ◽

Pain Crisis

Abstract An 18-year-old African-American male with sickle cell disease (SCD) is admitted to the hospital with a vaso-occlusive pain crisis affecting his chest and right upper extremity. He has a history of asthma but does not have a fever or respiratory symptoms, and a chest X-ray is negative for an infiltrate. He is treated with intravenous fluids and morphine. You are asked about the potential efficacy of systemic corticosteroids as an adjunctive treatment for pain control.

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Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis

Blood ◽

10.1182/blood-2018-99-118977 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4909-4909

Author(s):

Timothy Klouda ◽

Nataly Apollonsky ◽

Deepti Raybagkar ◽

Bruce Bernstein

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Acute Pain ◽

Neutrophil Count ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

History Of ◽

Pain Crisis ◽

Hematological Changes

Abstract Title: Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis Authors: Timothy Klouda1, Deepti. Raybagkar2, Bruce Bernstein1, Nataly Apollonsky2, Institutes:1Pediatrics, St Christopher's Hospital for Children, Philadelphia, PA, United States, 2Hematology, St Christopher's Hospital for Children, Philadelphia, PA, United States, Introduction: Children with Sickle Cell Disease suffer from multiple complications including acute pain crisis (VOC) and acute chest syndrome (ACS). Nearly 30% of children with SCD have had one episode of ACS, with the incidence higher in early childhood. The proposed pathophysiology of ACS is thought to be multi-factorial, with pulmonary fat embolism or infectious etiology being identified in a large number of patients. Increased sickling due to hypoxemia or pain has been shown to place patients at risk for ACS development., Studies have shown an increase in inflammatory markers including leukocytes and neutrophils, along with a decreased hemoglobin in SCD children who developed ACS, but no studies to date have compared laboratory changes during the acute illness to their baseline values. We hypothesized that children with SCD who are admitted for ACS will have a larger decrease in hemoglobin from baseline and a higher increase in white blood cell count from baseline when compared to those admitted for an acute pain crisis. Methods: Through retrospective chart review of patients with SCD admitted to St.Christopher's Hospital for Children we identified 45 patients with ACS. Laboratory data collected on admission from chart review included SCD genotype, age, BMI, hemoglobin, white blood cell count, absolute neutrophil count, absolute eosinophil count, platelets, reticulocyte count, hemoglobin F, vital signs and medication history. All 45 children had laboratory data collected from an acute pain crisis that occurred during a different admission for comparison. Collected data was compared to baseline laboratory data, collected during routine visit at sickle cell clinic within 1 year of admission. Changes in laboratory data from baseline during admission for ACS were compared to changes during admission for uncomplicated VOC. Results: Children with SCD who were admitted or developed ACS during admission had a larger increase in leukocyte count (6.99 vs 4.18, p=0.027) and neutrophil count (6.3 vs 3.74, p=0.04) from baseline compared to those admitted for VOC alone. Patients with ACS development also had a larger decrease in platelets (-124.74 vs -56.21, p=.047) from baseline when compared to VOC admissions. There was no statistically significant change from baseline labs when comparing hemoglobin (p=0.10), eosinophil count (p=.382), reticulocyte count (p=0.754), AST (p=0.061) and ALT (p=0.082) in the ACS and VOC groups. Children with a history of 2 or more lifetime ACS were more likely to have OSA (p=0.021), 3 or more VOCs in the past year (p=0.002), and a history of splenectomy, but it was not found to be statistically significant (p=0.155) Conclusion: Children with SCD who developed or were admitted with ACS had a significant increase in leukocyte and neutrophil count from baseline, and a decrease in platelets when compared to VOC admissions. There was no significant change from baseline in hemoglobin, reticulocyte and eosinophils detected. Future larger and multi-center prospective studies need to be performed to confirm the various changes identified in hematological markers seen in ACS vs VOC. Disclosures No relevant conflicts of interest to declare.

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Exchange Transfusion In Adult Patients With Sickle Cell Disease With Refractory Vaso-Occlusive Crises

Blood ◽

10.1182/blood.v122.21.4689.4689 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4689-4689 ◽

Cited By ~ 1

Author(s):

Padmini Moffett ◽

Bryan K Moffett

Keyword(s):

African American ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Exchange Transfusion ◽

Iron Chelation ◽

Adult Patients ◽

Cell Disease ◽

Psychological Burden ◽

Ed Visits

Sickle cell disease occurs in 1/500 African-American births. Pain is one of the most common complications of sickle cell disease and is associated with depression, anxiety, decreased quality of life and poor sleep patterns. Vaso-occlusive crises resulting in three or more hospitalizations per year occur in 48% of patients with sickle cell disease (Annals of Emergency Medicine - May 2009 (Vol. 53, Issue 5, Pages 587-593). Hydroxyurea has been shown to ameliorate the frequency of painful vaso-occlusive crises in sickle cell anemia (Charache et al, Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia NEJM. 1995), unfortunately many eligible patients are not treated due to psychosocial reasons and fear of teratogenicity or malignancy or have painful crisis refractory to hydroxyurea. A panel of experts has suggested that RBC exchange transfusion in these patients may decrease ED visits and subsequent hospitalizations based on anecdotal evidence [Best practices for transfusion for pateitns with sickle cell disease. T Wun, K Hagel. Hematology Review 2009, July 1; 1(22); e22]. We present the case of a 31 year old African-American male with Hgb S/beta thalassemia + with complications of sickle cell disease including Parvovirus B19 induced aplastic anemia, iron overload secondary to multiple simple transfusions, multiple vaso-occlusive crises as well as a left lower extremity ulcer precipitated by treatment with hydroxyurea. He was treated with folic acid as well as deferasirox for iron chelation. He began PRBC exchange transfusions every 6 weeks in March of 2011. In the one year prior to exchange transfusion initiation he had 13 ED visits and 4 hospitalizations for vaso-occlusive crises. After initiation of exchange transfusions he had 11 ED visits and 2 hospitalizations for vaso-occlusive crises the following year. An elevated WBC is associated with poor outcomes in sickle cell disease (Miller et al Predictors of adverse outcomes in children with sickle cell disease. N Engl J Med 2000). His average WBC level was 13 x 109/L, which decreased to 11 x 109/L after initiation of exchange transfusion. The patient underwent extended typing for E,C, and Kell RBC antigens to minimize development of antibodies. Though monthly exchange transfusions are costly and carry the attendant risk of antibody formation, this may be offset by reducing the financial and psychological burden of frequent hospitalizations for management of refractory vaso-occlusive crises. Exchange transfusion may also ameliorate the cost associated with long-term iron chelation. Further investigation is warranted to determine whether a program of monthly exchange transfusions can curtail ED visits and hospitalizations in adult patients with sickle cell disease and multiple, refractory vaso-occlusive crises. Disclosures: No relevant conflicts of interest to declare.

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Impact of Autoimmune Disease and Its Treatment on Adults with Sickle Cell Disease

Blood ◽

10.1182/blood-2021-153233 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4182-4182

Author(s):

Jennel Zeppieri ◽

Desmond Aroke ◽

Alice J. Cohen

Keyword(s):

Autoimmune Disease ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Low Dose ◽

Adult Patients ◽

High Dose ◽

Complement Pathway ◽

Cell Disease ◽

Pain Crisis ◽

Ed Visits

Abstract Background: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. Within the United States, it affects 1 in 100,000 people and 1 in 365 African American births. Management requires a comprehensive team dedicated to improving quality of life by minimizing the frequency of pain crisis, hospitalizations and infections that ultimately can reduce mortality. Susceptibility to infections among SCD patients is partly attributed to impaired host defense from chronic activation of the alternative complement pathway. This complement pathway dysregulation has also been suggested to predispose SCD patients to an array of autoimmune diseases (AID). It has been reported that the prevalence of AID in SCD teens and adults is 1.8%. The overlapping clinical manifestations and hematological abnormalities represent a challenge in diagnosing a coexisting AID among SCD patients and likely contribute to an under-reporting of its prevalence in the literature. Once coexistence is established, optimizing the management of each disease is challenging as the therapeutic treatment particularly the use of high dose steroids may exacerbate complications of SCD. The aim of this study was to assess the impact of AID and its treatment on SCD outcomes. Methods: In our retrospective review of 300 adult patients cared for in the adult SCD center from 2016-2021 we identified four patients (1.3%) who met the criteria of SCD and a confirmed diagnosis of an AID. Data that was reviewed included: age, type of SCD, type of AID, treatments of both, number of hospitalizations and ED visits and complications. Results: Four patients, all women between the ages of 38-42 years at the time of AID diagnosis, were identified. The coexisting SCD type and AID were as follows: HbSS with hereditary persistent of HbF(HPFH) and systemic lupus erythematous (SLE), HbSC and SLE with Sjogren's disease, S beta thalessemia+ and SLE with Raynaud's phenomena and HbSS with rheumatoid arthritis (RA). None of the patients were on hydroxyurea. None of the patients were treated with high dose steroids for their AID. Patient 1: HbSS/HPFH with infrequent hospitalizations for vasoocclusive pain crisis (VOC) A rash noted during her second pregnancy prompted a skin biopsy, revealing cutaneous SLE for which treatment with hydroxychloroquine (HC) was initiated. She had one admission for VOC pain crisis at 34 weeks of gestation. Her HC was discontinued prior to delivery. She had an elective C-section at 39 weeks and delivered a healthy 7 lb. baby. 6 weeks post partum she developed severe joint pains and fatigue. She experienced symptom relief with resumption of HC and a low dose prednisone (P) 10 mg. No additional immunosuppressive therapy was started as she continues to breast-feed. Patient 2: HbSC, with SLE and Sjogrens disease with frequent ED visits and admissions for VOC prior to her AID diagnosis. At AID diagnosis she was started on HC and pilocarpine resulting in a prompt reduction in ED visits for pain. She then began to experience worsening arthropathy presumed to be secondary to SLE and was started on methotrexate (MTX). She was hospitalized for community-acquired pneumonia /acute chest syndrome with pleural effusion and pulmonary infiltrates. After no response to antibiotics, she was started on P 30 mg with relief. Because of SLE flare with steroid taper and concern for high dose steroids she was started on rituximab 375 mg/m2 weekly x4. Her pulmonary infiltrates resolved. She continues to have frequent ED/admissions for pain events for VOC. Patient 3: HbSS with frequent ED/admissions for VOC prior to her diagnosis of RA, AVN and pulmonary hypertension. Her AID was treated with MTX and low dose P. Because of RA progression she started etanercept. She had 1 episode of sepsis and septic arthritis and continues to have frequent VOC. Patient 4: Sb+thalassemia with infrequent VOC diagnosed with SLE with Raynaud phenomena. She has been treated with HC without VOC but frequent urinary tract infections. Conclusion: Optimal treatment of adult patients with coexisting SCD and an AID is challenging. In this small group of patients, treatment with a variety of immunosuppressive agents other than high dose steroids, has led to control of the autoimmune disease but no clear improvement of sickle cell pain events and some atypical infections have occurred. Continued tracking of cases of SCD with AID should be done to better understand management and long term outcomes. Disclosures No relevant conflicts of interest to declare.

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Transcranial Doppler Screening Adherence Among Children with Sickle Cell Anemia Seen in the Emergency Department

Blood ◽

10.1182/blood-2018-99-115057 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3569-3569

Author(s):

Julie K. Weisman ◽

Carrie Diamond ◽

Sarah Kappa ◽

Robert Sheppard Nickel

Keyword(s):

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Transcranial Doppler ◽

Clinic Visit ◽

Cell Disease ◽

Screening Guidelines ◽

History Of ◽

Screening Adherence

Abstract Background: Annual transcranial doppler (TCD) screening is strongly recommended for patients with sickle cell anemia (SCA) between the ages of 2 to 16 years to identify children at highest risk for stroke. Implementation of this screening and treating identified patients with chronic transfusion has decreased the incidence of overt stroke. Nonetheless, adherence to TCD screening guidelines is poor and many children with SCA do not receive an annual TCD. The purpose of this study is to evaluate adherence to TCD screening among a cohort of patients with SCA seen in the emergency department (ED) for an acute problem. Previous work has demonstrated that SCD-related outpatient visits are important "missed opportunities" for TCD screening. We hypothesized that ED encounters also represent potential opportunities to identify patients in need of TCD screening who do not attend clinic regularly. Methods: We conducted a retrospective chart review of the medical records of all patients with sickle cell disease (SCD) seen in the ED at a large, urban pediatric institution between February 2016 and April 2017. Patients were identified using an ED clinical registry that includes all ED patient encounters. We excluded patients who do not need TCD screening (sickle cell disease genotypes other than SS and Sβ0 thalassemia, age <2 or >16 years, on chronic transfusions, history of hematopoietic stem cell transplant). We also excluded patients documented to previously have inadequate TCD bone windows and patients who did not receive their regular hematology care at the study institution. For eligible patients who had multiple ED encounters during the study period, data was extracted at the time of the first ED encounter during the study period. Eligible patients who had received a TCD in the last year (adherent to TCD screening) were compared to patients who had not received a TCD in the last year (nonadherent to TCD screening). Categorical data was analyzed with the chi-square test. Continuous data was analyzed using the two-sample t-test. P value of <0.05 was considered statistically significant. Results: During the 64 week study period, 739 patients with SCD were seen in the ED. A total of 482 patients were excluded for the following reasons: non-SCA genotype (n=164), age (n=139), followed at outside institution (n=129), chronic transfusion (n=38), prior TCD window problem (n=10), history of transplant (n=2); leaving 257 patients with SCA aged 2-16 years for study. Among this study group, 63 patients (25%) had not received a needed TCD in the last year, including 19 patients (7%) who had never had a TCD. When excluding patients aged 2-2.99 years (n=33) in whom a first TCD may have been planned soon after the ED encounter, a similar proportion of patients still had not received a TCD in the last year (53/224, 24%) but a slightly smaller proportion had never had a TCD (9/224, 4%). Patient age and sex were not associated with TCD screening adherence (p>0.7). Patients adherent to TCD screening were more likely to be taking hydroxyurea (67% vs. 29%, p<0.0001). A recent hematology clinic visit was significantly associated with TCD screening adherence. All patients adherent to TCD screening had a clinic visit in the last year compared to 75% of nonadherent patients, p<0.0001. The mean interval time since the last hematology clinic appointment from the ED encounter was greater for TCD nonadherent patients, 70 vs. 270 days p<0.0001 (Figure). Conclusion: Patients with SCA who present to the ED and are nonadherent to TCD screening guidelines are less likely to have had a recent hematology clinic visit. Therefore, the ED may be an important location for identifying patients lost to regular clinic follow-up in need of a TCD. An intervention that specifically targets this patient population will likely improve TCD screening rates and stroke prevention. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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