Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq

Beneficial effects of adenotonsillectomy in children with sickle cell disease

ERJ Open Research ◽

10.1183/23120541.00071-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00071-2020

Author(s):

Ilaria Liguoro ◽

Michele Arigliani ◽

Bethany Singh ◽

Lisa Van Geyzel ◽

Subarna Chakravorty ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Arterial Oxygen Saturation ◽

Arterial Oxygen ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Beneficial Effects ◽

Admission Rates ◽

The Mean ◽

The Impact

Tonsillectomy and adenoidectomy (T&A) is frequently performed in children with sickle cell disease (SCD). Our aim was to evaluate the impact of this surgery on overnight oxygenation and rates of complications in these patients.Children with SCD who underwent T&A between 2008 and 2014 in two tertiary hospitals were retrospectively evaluated. Overnight oximetry and admission rates due to vaso-occlusive pain episodes (VOEs) and acute chest syndrome (ACS) in the year preceding and following the surgery were compared.19 patients (10 males, 53%) with a median age of 6 years (range 3.5–8) were included. A significant increase of mean overnight arterial oxygen saturation measured by pulse oximetry (SpO2) (from 93±3.6% to 95.3±2.8%, p=0.001), nadir SpO2 (from 83.0±7.1% to 88±4.1%, p=0.004) and a reduction of 3% oxygen desaturation index (from a median value of 5.7 to 1.8, p=0.003) were shown. The mean annual rate of ACS decreased from 0.6±1.22 to 0.1±0.2 events per patient-year (p=0.003), while the mean cumulative rate of hospitalisations for all causes and the incidence of VOEs were not affected.T&A improved nocturnal oxygenation and was also associated with a reduction in the incidence of ACS at 1-year follow-up after surgery.

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Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.4767.4767 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4767-4767

Author(s):

Giovanna Graziadei ◽

Alessia Marcon ◽

Martina Soldarini ◽

Ilaria Gandolfi ◽

Luisa Ronzoni ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Acute Chest Syndrome ◽

P Value ◽

Cell Disease ◽

Transfusion Therapy ◽

Clinical Complications ◽

Significant Difference ◽

The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

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Comparison of Clinical Evolution of Children with Sickle Cell Disease before and after Treatment with Hydroxyurea at Saint Damien Hospital, Tabarre-Haiti,2013-2018

Blood ◽

10.1182/blood-2019-124105 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2306-2306

Author(s):

Nora St Victor Dély ◽

Ofelia A. Alvarez ◽

Vanessa J Dor ◽

Emmeline Lerebours

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Course ◽

Acute Chest Syndrome ◽

Blood Transfusions ◽

Cell Disease ◽

Clinical Evolution ◽

Before And After ◽

The Mean ◽

Painful Crisis

INTRODUCTION Sickle cell disease (SCD), an autosomal recessive hemoglobinopathy, is associated with a high morbidity and mortality rate, especially in low income countries. In Africa, 5% of deaths among children under five are attributable to SCD [59th World Health Assembly, WHO 2006]. This chronic disease greatly alters the quality of life of affected children. However, according to several published studies, SCD clinical course can be improved with the administration of hydroxyurea, an antimetabolite drug. [Nkashama, Pan African Medical Journal,2015] Saint-Damien, a pediatric hospital in Haiti, has a current cohort of 1248 sickle cell children. Forty of them (3 %) benefit from hydroxyurea administration since November 2015. In this hospital, data on how hydroxyurea modifies SCD clinical course are lacking, despite the advantage of this drug described in literature [Charache,New England Journal of Medicine,1995]. This study aims to compare the evolution of children treated at Saint Damien Hospital, before and after receiving hydroxyurea. METHODS A retrospective analytic study was conducted from November 2013 to June 2018 in the Sickle Cell Clinic at Saint-Damien Hospital. We included 40 children aged 2 to 15 years old treated with hydroxyurea. All of them benefit of the same treatment protocol: Initial dose of 10 mg per kg per day increase to maintenance dose of 25 mg per kg per day. Any child whose treatment has been permanently discontinued regardless of the cause was excluded. Epidemiological and clinical data were collected using Excel 2010. We compared children clinical evolution two years before and two years after hydroxyurea administration using these parameters: frequency and duration of hospitalizations, hospitalization frequency for specific complications (pain crisis, stroke and acute chest syndrome), and frequency of blood transfusions. We calculated frequencies, ratios and means using Epi Info. We realized statistical analysis to compare quantitative variables with a p value significant when less than 5%. RESULTS Gender ratio was 1:1. The mean age of children at enrollment on hydroxyurea was 8 years. Thirty-eight children of 40 (95 %) experienced at least one hospitalization before receiving the drug, compared with 17 (42.5%) after, p=0.025. The mean duration of hospitalization was 9 days before and 6 days after, p=0.0319. The average number of hospitalizations per child was decreased by 30 %. Seventy percent of children were hospitalized at least once due to painful crisis 2 years before receiving hydroxyurea, compare to 22.5 % after. Thirty-one children (77.5%) were transfused at least once before receiving the drug and 9 (22.5%) after receiving it. There was no cases of acute chest syndrome or stroke reported after hydroxyurea, unlike before the introduction of the drug. (Table 1) CONCLUSION The percentage of hospitalized children and the average length of hospitalization stay decreased significantly with hydroxyurea intake; as well as the frequency of painful crisis and blood transfusions. Hydroxyurea acts directly on the two main causes of hospitalization in the sickle cell, reducing the morbidity related to this pathology; and demonstrating the direct benefit of this drug at Saint Damien Hospital. Since our cohort is young, we have not been able to follow his evolution over a longer period of time. We plan to continue to observe this cohort. But these first results already allow us to recommend a broader use of hydroxyurea for pediatric patients with SCD in Haiti. Disclosures Alvarez: Forma Therapeutics: Consultancy; Novartis: Consultancy.

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Progression of Pulmonary Hypertension in Patients with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3187.3187 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3187-3187 ◽

Cited By ~ 3

Author(s):

Kenneth I. Ataga ◽

Charity Moore ◽

Susan Jones ◽

Oludamilola Olajide ◽

Dell Strayhorn ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Left Ventricular ◽

Right Atrial ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Original Cohort ◽

The Mean

Abstract Introduction: The prevalence of pulmonary hypertension (PHT) is high in patients with sickle cell disease (SCD). Although most patients have only mild increases in their pulmonary artery systolic pressure (PASP), the presence of PHT is strongly associated with an increased risk of death. While PHT seen in SCD is thought to progress over time, both the rate of development of PHT and the factors that affect disease progression remain unknown. Methods: The 41 subjects in this study were drawn from an original cohort of 60 patients followed in the Sickle Cell Clinic at UNC-Chapel Hill. All patients were previously evaluated for PHT (defined using an age-, sex-, and BMI-adjusted reference range). Of the 60 patients in the original cohort, six are now deceased and 13 others were not available for repeat evaluation. The PASP was determined using Doppler echocardiography and then applying the modified Bernoulli equation (PASP = 4V2 + right atrial pressure). Individuals were not studied if they: 1) showed clinical evidence of left ventricular failure; 2) had a recent acute illness (e.g., vaso-occlusive crisis); or 3) had experienced an episode of acute chest syndrome within the preceding 4 weeks. Means and standard deviations were calculated for all measures at the time of initial evaluation and at the time of follow-up. Results: Of the 41 subjects in our study, PHT was originally present in 12, while no evidence of PHT was present in 29. Of the 29 subjects who initially had no evidence of PHT, 4 (or 14%) have now developed PHT (mean follow-up period of 3.3 ± 0.4 years). In these 4 subjects, the mean PASP at the time of initial and follow-up evaluations respectively were: 37.0 ± 2.0 mm Hg vs. 55.8 ± 11.0 mm Hg. The patients who developed PHT during the course of the study had lower systolic BP (143 ± 12 mm Hg vs. 128 ± 12 mm Hg), lower fetal hemoglobin levels (6.2 ± 5.7 % vs. 4.2 ± 3.7 %), and higher platelet counts (276 ± 119 X 103/μL vs. 426 ± 96 X 103/μL) at the time of their follow-up analyses. By contrast, 3 of the 12 subjects (or 25%) who were thought to have PHT at the time of their original evaluations were found to have normal PASP determinations at the time of their repeat echocardiograms (mean follow-up period of 3.2 ± 0.6 years). In these latter 3 subjects, the mean PASP values at the time of the initial and follow-up evaluations respectively were: 40.0 ± 4.6 mm Hg vs. 33.7 ± 4.7 mm Hg. Conclusion: In this small group of patients with SCD, we found that PHT developed in 14% of subjects who had no evidence of PHT 3 years earlier. Based on this observation, it seems that periodic echocardiograms to screen for the development of PHT would be appropriate. On the other hand, our observation that some patients initially classified as having PHT failed to have elevated PASP measurements at the time of follow-up illustrates the limitation of a single echocardiographic evaluation in establishing this diagnosis. Because of the increase in PASP that occurs during acute vaso-occlusive episodes, and the difficulty usually encountered in distinguishing steady state from crisis, the initial elevation of the PASP in these patients could have resulted from sub-clinical crisis states. For these reasons, a patient found to have an elevated PASP at the time of a screening echocardiogram should have a repeat study, and perhaps a right heart catheterization, before the diagnosis of PHT is firmly established.

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Treatment patterns and economic burden of sickle-cell disease patients prescribed hydroxyurea: a retrospective claims-based study

Health and Quality of Life Outcomes ◽

10.1186/s12955-019-1225-7 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 8

Author(s):

Nirmish Shah ◽

Menaka Bhor ◽

Lin Xie ◽

Rashid Halloway ◽

Steve Arcona ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Economic Burden ◽

Medication Possession Ratio ◽

Treatment Patterns ◽

Care Utilization ◽

Acute Chest Syndrome ◽

Cell Disease ◽

The Mean

Abstract Background This study aimed to evaluate sickle-cell disease (SCD) treatment patterns and economic burden among patients prescribed hydroxyurea (HU) in the US, through claims data. Methods SCD patients with pharmacy claims for HU were selected from the Medicaid Analytic Extracts (MAX) from January 1, 2009 - December 31, 2013. The first HU prescription during the identification period was defined as the index date and patients were required to have had continuous medical and pharmacy benefits for ≥6 months baseline and 12 months follow-up periods. Patient demographics, clinical characteristics, treatment patterns, health care utilization, and costs were examined, and variables were analyzed descriptively. Results A total of 3999 SCD patients prescribed HU were included; the mean age was 19.24 years, most patients were African American (73.3%), and the mean Charlson comorbidity index (CCI) score was 0.6. Asthma (20.3%), acute chest syndrome (15.6%), and infectious and parasitic diseases (20%) were the most prevalent comorbidities. During the 12-month follow-up period, 58.9% (N = 2357) of patients discontinued HU medication. The mean medication possession ratio (MPR) was 0.52, and 22.3% of patients had MPR ≥80%. The average length of stay (LOS) for SCD-related hospitalization was 13.35 days; 64% of patients had ≥1 SCD-related hospitalization. The mean annual total SCD-related costs per patient were $27,779, mostly inpatient costs ($20,128). Conclusions Overall, the study showed the patients had significant unmet needs manifest as poor medication adherence, high treatment discontinuation rates, and high economic burden.

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A Pilot Study of Eptifibatide for Treatment of Acute Pain Episodes in Sickle Cell Disease.

Blood ◽

10.1182/blood.v120.21.2102.2102 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2102-2102

Author(s):

Payal C Desai ◽

Julia Brittain ◽

Susan Jones ◽

Adam McDonald ◽

Douglas R Wilson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Acute Pain ◽

Research Funding ◽

Point Estimate ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Opioid Use ◽

Advisory Committees

Abstract Abstract 2102 Background: Despite the abundant laboratory evidence of platelet activation and inflammation in sickle cell disease (SCD), the contribution of these changes to the pathogenesis of SCD remains uncertain. Patients with SCD exhibit increased platelet activation in the non-crisis, “steady state,” and further increases with acute pain episodes. In addition, levels of the inflammatory mediator, CD40 ligand (CD40L) are increased in the plasma and significantly reduced in the platelets of SCD patients compared to healthy individuals. CD40L may contribute to the pathogenesis of acute pain episodes. Despite an improved understanding of the pathophysiology of SCD, the treatment of acute pain episodes is supportive. We performed a randomized, placebo-controlled study to evaluate the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the glycoprotein (GP) IIb/IIIa receptor, in patients with SCD during acute painful episodes. Methods: In this single site placebo-controlled trial, eligible patients admitted for acute painful episodes received eptifibatide (two 180 mg/kg boluses 10 minutes apart, followed by a continuous infusion at 2 mg/kg/min for 6 hours) or placebo at a ratio of 2:1. The Post-Treatment Phase lasted for up to 7 days or until resolution of the crisis, whichever was shorter, but no less than 24 hours after discontinuation of infusion. The Follow-up Phase included safety evaluations obtained 14 to 17 days and 28 to 35 days after discontinuation of infusion. The primary outcomes were major bleeding episodes and the largest observed decrease in platelet count during the study. We also evaluated the effect of eptifibatide on the duration of acute pain episodes, pain intensity, duration of hospitalization, total opioid use and acute chest syndrome. Results: Thirteen patients (SS - 10, Sb0 - 2, SC - 1) were randomized to receive either eptifibatide (N=9; 6 females; median age - 25 years) or placebo (N=4; 3 females; median age - 31 years). One patient in the eptifibatide arm withdrew consent following completion of study drug infusion and 1 patient in the placebo arm was withdrawn early because she did not meet eligibility criteria. In the intent-to-treat analysis, there were no major bleeding episodes in either group (point estimate of difference in eptifibatide vs. placebo proportion: 0.0, 95% CI; −0.60, 0.37).There was one minor bleeding episode in a patient on the eptifibatide arm (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.502, 0.494). There was a trend for the largest decrease in platelet count to be greater in the eptifibatide arm compared to the placebo arm, although the difference was not statistically significant (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −82, 95% CI; −281, 54). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.587, 0.495). The median time to discharge and the median time to crisis resolution were 3.0 days for both treatment arms. The median total opioid use was 400.2 morphine equivalents (ME) for the eptifibatide group and 1471 ME for the placebo group (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −65.8, 95% CI: −2519, 1700). There was one episode of acute chest syndrome in each treatment arm. Conclusions: In this small study of SCD patients hospitalized with acute painful episodes, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Eptifibatide was associated with a reduced requirement for opioid analgesics, although the difference was not statistically significant. Clinicaltrials.gov Identifier: NCT00834899. Disclosures: Parise: BD: Consultancy; Biogen-Idec: Consultancy; NIH: Research Funding; AHA: Research Funding; SCDAC-NIH: Membership on an entity's Board of Directors or advisory committees; BRI Milwaukee: Membership on an entity's Board of Directors or advisory committees. Ataga:Pfizer: Consultancy; HemaQuest Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adventrx Pharmaceuticals: Consultancy. Off Label Use: Eptifibatide, a glycoprotein IIb/IIIa inhibitor, was evaluated as treatment for acute pain episodes in patients with sickle cell disease.

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

Blood ◽

10.1182/blood-2020-141359 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 38-39

Author(s):

Laurence Noisette ◽

Mamatha Mandava ◽

Mathew Gregoski ◽

Shayla Bergmann

Keyword(s):

South Carolina ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Presentation ◽

Self Report ◽

Mortality Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

History Of ◽

The Mean

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), first identified in Wuhan, China, was declared a pandemic by WHO in March 2020 due to its high transmission rate. Due to the diffuse vasculo-endothelial damage, individuals with Sickle Cell Disease (SCD) are at risk to develop severe clinical complications, if infected with coronavirus 19 (COVID-19).[1] Given this risk, a systematic evaluation of individuals with SCD presenting with COVID19 infection is paramount to identify the variable clinical manifestations and complications encountered in children and adults with SCD. Methods: A retrospective chart review was conducted from January to June 2020 at the Medical University of South Carolina. We included individuals with sickle cell disease of all genotypes, from 0 to 65 years of age found to be positive for COVID19 by polymerase chain reaction (PCR). Patients' past medical history, clinical presentations, admissions, treatment, complications, and mortality data were reviewed. The data was collected with REDCap@ and descriptive data analysis was conducted per SPSS@. Results: Of the identified 23 patients with SCD who tested positive for COVID during the time specified, 19 (82.6%) had Hgb SS genotype, two had Hgb SC (9%) and two Hgb Sβ+ thalassemia (9%) with similar incidence in both genders (47.8% male and 52.2 % female). All patients were African American. The mean age was 26.13+/-11.53 years. In the last three years they had admissions for pain at a mean of 4.29 +/- 5 and admissions for acute chest syndrome 1+/- 2.2. Six participants (26.1%) had history of mild asthma. Two (8.7%) had pulmonary hypertension. No participants had a history of silent stroke. One participant had history of ischemic stroke, three (13%) had history of pulmonary embolism, and six (26.1%) had deep vein thrombosis (DVT). A variable clinical presentation was noted in our population (Table 1). Of the 23, only nine (39%) required admission of which only one met criteria for intensive care (4.3%) requiring respiratory support with high flow nasal canula. All participants recovered well with the mean length of admission 4.36+/- 3.8 days. Treatment included supportive care including transfusion support, two (8.7%) needed simple transfusion, two (8.7%) needed exchange transfusion. Regarding the laboratory values, coagulations studies were noted to be elevated among all those obtained, but overall limited values were obtained. (Table 2) Thus far no complications of stroke, thrombosis, or pulmonary emboli are noted in the patients positive for COVID in sickle cell disease at our institution. No deaths were reported. Conclusion: Our population reflects what has been described thus far in other cohorts regarding patient demographics, clinical presentation and evolution of disease. Missing laboratory results is most likely due to the mild severity which did not require further clinical evaluation. The absence of VTE/PE may be explained by the low rate of ICU admissions. A similar ICU admission rate of 13% in the same age group as our population was described in a study conducted in France with 83 patients. [2] Compared to a study conducted in Detroit, Michigan, our population underwent comparable rates of transfusions with 3 patients compared to 4 in our population, again most likely due to the mild severity. [3] Our results reflect only MUSC's testing sites and we are dependent on patient's self-report which may not represent our entire population. To address this issue, as part of the Sickle Cell South Carolina network, we are partnering with two other institutions to assess SARS-Cov-2 infection in South Carolina. SARS-CoV-2 pandemic has brought to light many disparities encountered in the American health care system. It is premature to evaluate the immediate and long-term ramifications of COVID19 in individuals with sickle cell disease, due to which we plan to continue to monitor for the next 2 years. References 1. Hussain, F.A., et al.,COVID-19 Infection in Patients with Sickle Cell Disease.Br J Haematol, 2020. 2. Arlet, J.B., et al.,Prognosis of patients with sickle cell disease and COVID-19: a French experience.Lancet Haematol, 2020. 3. Balanchivadze, N., et al.,Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease. One Center Urban Experience, Detroit, MI, USA.Hemoglobin, 2020: p. 1-6. Disclosures Gregoski: National Institutes of Health under Grant Number UL1 TR001450:Current Employment.

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Efficacy and Safety of Manual Partial Red Cell Exchange in the Management of Severe Complications of Sickle Cell Disease in a Developing Country

Advances in Hematology ◽

10.1155/2017/3518402 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

B. F. Faye ◽

D. Sow ◽

M. Seck ◽

N. Dieng ◽

S. A. Toure ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Blood Count ◽

Acute Chest Syndrome ◽

Red Cell ◽

Efficacy And Safety ◽

Cell Disease ◽

Resource Setting ◽

Low Resource Setting ◽

The Mean

Introduction. The realization of red cell exchange (RCE) in Africa faces the lack of blood, transfusion safety, and equipment. We evaluated its efficacy and safety in severe complications of sickle cell disease. Patients and Method. Manual partial RCE was performed among sickle cell patients who had severe complications. Efficacy was evaluated by clinical evolution, blood count, and electrophoresis of hemoglobin. Safety was evaluated on adverse effects, infections, and alloimmunization. Results. We performed 166 partial RCE among 44 patients including 41 homozygous (SS) and 2 heterozygous composites SC and 1 S/β0-thalassemia. The mean age was 27.9 years. The sex ratio was 1.58. The regression of symptoms was complete in 100% of persistent vasoocclusive crisis and acute chest syndrome, 56.7% of intermittent priapism, and 30% of stroke. It was partial in 100% of leg ulcers and null in acute priapism. The mean variations of hemoglobin and hematocrit rate after one procedure were, respectively, +1.4 g/dL and +4.4%. That of hemoglobin S after 2 consecutive RCE was −60%. Neither alloimmunization nor viral seroconversion was observed. Conclusion. This work shows the feasibility of manual partial RCE in a low-resource setting and its efficacy and safety during complications of SCD outside of acute priapism.

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A Short Course of Prednisone in the Management of Acute Chest Syndrome of Sickle Cell Disease.

Blood ◽

10.1182/blood.v112.11.1417.1417 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1417-1417

Author(s):

Riten Kumar ◽

Shahina Qureshi ◽

Prita Mohanty ◽

Sreedhar P Rao ◽

Scott T. Miller

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Steroid Therapy ◽

Readmission Rate ◽

Clinical Severity ◽

Acute Chest Syndrome ◽

Cell Disease ◽

The Past ◽

Short Course ◽

Increased Risk

Abstract Background: Acute chest syndrome is defined as the presence of acute pulmonary findings in an individual with sickle cell disease. A brief course of dexamethasone was shown to significantly attenuate the course of mild to moderate ACS, but treated patients appeared to have an increased risk of readmission, generally for pain episodes, as compared to controls (31.5% vs. 4.7%; p=0.09). In a more recent retrospective review of patients with ACS, the readmission rate was even more alarming, with 59% of patients who received steroids alone (without transfusion) readmitted, again primarily for vaso-occlusive pain episodes. Over the past several years low dose steroid therapy [1–2mg/kg (maximum 80mg) of prednisone for 3 – 7 days] has been embraced as routine care for ambulatory and hospitalized patients with status asthmaticus. Potentially deleterious effects of steroid therapy, namely immunosuppression, especially in patients with concurrent pneumonia, and rebound wheezing after discontinuation of therapy have not been problematic. We reasoned that such a regimen to treat ACS might be beneficial without a “rebound effect” potentially leading to pain episodes, and over the past several years have increasingly used an asthma regimen of steroid therapy in our ACS patients who showed worsening clinical severity. Methods: Admissions recorded in a Pediatric Hematology – Oncology inpatient register were reviewed from July 1, 2005 to June 30, 2007 to identify patients hospitalized at the University Hospital of Brooklyn and King’s County Hospital Center with ACS; the register included children with ACS on admission and those who developed ACS during hospitalization for other complications. The clinical course of patients who received prednisone was compared to those who did not, particularly to assess the frequency of early (within two weeks) readmission after discharge. Results: Between July 2005 and June 2007, 63 patients were admitted for 78 episodes of ACS. Fifty-three patients received prednisone and 25 did not. Prednisone was used more frequently in patients with moderate or severe ACS (p<0.001). Eight patients (15.1%) who received prednisone were re-admitted within 2 weeks versus two (8.3%) who did not receive steroids (p=0.41). Overall the duration of hospital stay was similar in both groups, 3.1 days in patients who did not receive steroids and 3.8 days in patients who did (p=0.13). Seventeen patients (21.8%) received a simple blood transfusion, fifteen in the prednisone group and two in the non prednisone group. None had exchange transfusion. No patient required mechanical ventilation. Conclusion: In our retrospective chart analysis, we did see re-admissions after short course prednisone therapy; however, the re-admission rate was not significantly greater than that seen in children not receiving steroids and lower than that previously reported. Duration of stay and transfusion frequency were no different between steroidtreated and untreated patients, though the former had more severe disease at diagnosis; this may suggest clinical benefit. In summary, it may be possible to achieve the previously documented beneficial effects of steroid therapy for ACS without an unacceptable readmission rate by adjusting the treatment regimen. An asthma regimen similar to that used here would be reasonable to assess in a large prospective trial.

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Determinants Of Heme-Oxygenase-1 Upregulation In Patients With Sickle Cell Disease

Blood ◽

10.1182/blood.v122.21.2235.2235 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2235-2235 ◽

Cited By ~ 2

Author(s):

Olufolake Adisa ◽

Benjamin Yaw Owusu ◽

Yijuan Hu ◽

Samit Ghosh ◽

Fang Tan ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Heme Oxygenase ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Dinucleotide Repeat ◽

Acute Chest Syndrome ◽

Heme Oxygenase 1 ◽

Cell Disease ◽

The Mean

Abstract Inflammation is a cardinal component of the pathogenesis of sickle cell disease (SCD). Increased plasma concentration of the inflammatory agonist hemin increases the odds of acute chest syndrome (ACS) in children with SCD (Adisa et al., Br. J Haematol, 2013). In addition, free hemin promotes the development of a lethal ACS-like disease in transgenic sickle mice (Ghosh et al., J Clin Invest, 2013). Hemin degradation is controlled by the rate-limiting enzyme heme oxygenase-1 (HO-1). Polymorphism of a (GT)n dinucleotide repeat in the HO-1 promoter, which enhances expression of the gene, is associated with lower rates of hospitalization for ACS in children. Over-expression of HO-1 reduces stasis in a mouse model of SCD vaso-occlusion. However, the role of plasma HO-1 in SCD patients is entirely unknown. In this study, we measured steady-state plasma HO-1 in two cohorts of patients. Cohort 1 in Atlanta (n=98) consisted of children with a mean age of 10.07±0.42 years (range 2-19 years) and cohort 2 from Accra (n=80) consisted of older patients (mean age 25.30±1.0 years, range 13-58 years). The mean plasma HO-1 of both cohorts was significantly higher compared to the mean value of age- and ethnic-matched individuals with normal adult Hb; Atlanta: 10.19±5.80 vs. 2.08± 1.16, p<0.0001 and Accra: 13.7±8.14 vs. 2.57± 0.82, p<0.0001. Plasma HO-1 varied by 25-fold in both cohorts and it correlated with the white blood cell count (Atlanta: r=0.3361, p<0.0001, Accra: r=0.25, p=0.02). Fifty-four percent (n=53) of subjects in the Atlanta cohort were on hydroxyurea. The mean plasma HO-1 of this subgroup was lower (8.1 ± 4.5) compared to the hydroxyurea naïve Accra cohort (p=<0.0001). Further studies of the Accra cohort revealed significant correlations between HO-1 and multiple markers of vascular inflammation; sICAM-1(r=0.2794, p=0.03, n=60), sE-selectin (r= 0.4209, p=0.0017, n=58) and sP-selectin (r=0.3855, p=0.0028, n=58). The number of the (GT)n dinucleotide in the HO-1 promoter ranged 17 to 45; the distribution was trimodal with peaks at 23, 30 and 41 repeats. The overwhelming majority of patients had medium and large size alleles that are generally hypo-response to induction. Plasma HO-1 level correlated with the length of the (GT)n dinucleotide repeat (p=0.003, n=80). In a multivariable regression model, WBC, sICAM-1, sE-selectin and sP-selectin accounted for 13.4% of the total variance of plasma HO-1 level, and the (GT)n polymorphism accounted for 9.8%. In conclusion, the concentration of plasma HO-1 is generally raised among SCD patients at steady-state. However, a large proportion of patients have a relatively modest level that is probably inadequate to counter the severity of inflammation typical of SCD, due in part to a hypo-responsive HO-1 promoter. Therapeutic strategies that complement induction of the endogenous HO-1 gene may be critical to ameliorate inflammation in SCD. Disclosures: No relevant conflicts of interest to declare.

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