Acute Chest Syndrome Cases Research Articles

Risk factors for acute chest syndrome among children with sickle cell anemia hospitalized for vaso-occlusive crises

Sickle cell anemia (SCA) is a globally prevalent inherited condition, with acute chest syndrome (ACS) being one of its most severe complications. ACS frequently leads to hospitalization, requires intensive care unit (ICU) admission, and can even result in death. This study aimed to discern the early indicators of impending ACS in children with SCA who were initially hospitalized due to painful vaso-occlusive crises (VOC). This was a retrospective, case‒control investigation of 120 patients aged 1–14 years seen at the King Saud Medical City in Riyadh, Saudi Arabia from January 2021 to December 2022. Patients were classified into cases and controls: those who developed and did not develop ACS during hospital stay, respectively. Demographic factors, laboratory results, vital and clinical signs, and treatment protocols were compared between these groups. The following were significant predictors of impending ACS: previous diagnosis of asthma, history of ACS, recent upper respiratory tract symptoms prior to admission, and need for a blood transfusion within the first 24 h of admission due to a drop in hemoglobin levels. Further regression analysis indicated that elevated steady-state mean corpuscular volume, leukocyte count, total bilirubin, and an increased absolute neutrophil count level 24 h after admission also foreshadowed impending ACS among patients admitted for VOC. The location of pain was also significant; the incidence of ACS was higher in patients with back pain, but lower in those with pain confined to the limbs. The ACS group had a longer average duration of hospital stay compared to those with VOC alone, (7.6 vs. 5.8 days). Among patients initially admitted for VOC, 15.7% were diagnosed with ACS. Most ACS cases were managed with transfusions and antibiotics, and nearly one-third of patients needed admission to an ICU or a high-dependency area.

Diagnostic Test Accuracy of Lung Ultrasound for Acute Chest Syndrome in Sickle Cell Disease: A Systematic Review and Meta-analysis

Acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease. Lung ultrasound (LUS) is emerging as a point-of-care method to diagnose ACS, allowing for more rapid diagnosis in the ED setting and sparing patients from ionizing radiation exposure. What is the diagnostic accuracy of LUS for ACS diagnosis, using the current reference standard of chest radiography? Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review and meta-analysis. Embase, MEDLINE, Web of Science, and Google Scholar were used to compile all relevant studies. Two reviewers screened the studies for inclusion in this review. Cases of discrepancy were resolved by a third reviewer. Meta-analyses were conducted using both metadta and midas STATA software packages to retrieve summary receiver operating characteristic curves, sensitivities, and specificities. Three reviewers scored the studies with QUADAS-2 for risk of bias assessment. From a total of 713 unique studies retrieved, six studies were included in the final quantitative synthesis. Of these, five studies were in pediatric EDs. Two studies were conference abstracts and not published manuscripts. Data were available for 625 possible ACS cases (97%of cases in patients aged≤ 21 years) and 95 confirmed ACS diagnoses (pretest probability of 15.2%). The summary sensitivity was 0.92 (95%CI, 0.68-0.98) and the summary specificity was 0.89 (95%CI, 0.69-0.97) with an area under the curve of the summary receiver operating characteristic curve of 0.96 (95%CI, 0.94-0.97). LUS has excellent sensitivity and very good specificity for ACS diagnosis and may serve as an initial point-of-care test to facilitate rapid treatment of ACS and spare pediatric patients from ionizing radiation; however, further research is warranted to improve the generalizability to the adult sickle cell disease population.

Suboptimal vancomycin levels in critically ill children with sickle cell disease and acute chest syndrome

ObjectivesThis is a pilot retrospective study to assess the effect of glomerular hyper-filtration (GHF) related to sickle cell disease (SCD) on vancomycin clearance and ultimately on therapeutic drug levels in children admitted to the pediatric intensive care unit (PICU) with acute chest syndrome (ACS). MethodThe patients’ steady-state vancomycin trough levels (VTL) and the area under the curve (AUC) were compared with those of age- and gender-matched control group; matching was made at a 1:3 ratio. ResultsTwelve SCD patients with ACS and treated with vancomycin were compared with 36 non-SCD patients (control group). Compared with the control patients, the ACS patients had significantly lower initial serum VTL (median = 6.00 mcg/mL vs. 9.75 mcg/mL) (p = 0.007), and their average VTL were still lower (median = 6.65 mcg/mL vs. 10.00 mcg/mL) post vancomycin dose adjustment (p = 0.039). The time to achieve the therapeutic vancomycin level was significantly longer for the ACS patients (median = 4.75 days) than for the control group (median = 1 day) (p = 0.009). The AUC was also significantly lower in the ACS patients (median = 293 mg*h/L) than in the control group (median = 405.5 mg*h/L) (p = 0.007). The AUC was negatively associated with creatinine clearance (Beta Coefficient = −0.366, p-value=<0.001) even when adjusted for receiving loading dose, standard dose per weight, and severity of critical illness. ConclusionThese findings support the attributed role of the GHF associated with SCD leading to lower vancomycin level in ACS cases. Therefore, the standard dosing approach for vancomycin in ACS patients may be ineffective. We thus advocate for individualized dosing with careful monitoring of drug levels to account for GHF.

Point‐of‐care lung ultrasound is more reliable than chest X‐ray for ruling out acute chest syndrome in sickle cell pediatric patients: A prospective study

Acute chest syndrome (ACS) is a leading cause of morbidity and mortality in sickle cell patients, and it is often challenging to establish its diagnosis. This was a prospective observational study conducted in a pediatric emergency (PEM) department. We aimed to investigate the performance characteristics of point-of-care lung ultrasound (LUS) for diagnosing ACS in sickle cell children. LUS by trained PEM physicians was performed and interpreted as either positive or negative for consolidation. LUS results were compared to chest X-ray (CXR) and discharge diagnosis as reference standards. Four PEM physicians performed the LUS studies in 79 suspected ACS cases. The median age was 8years (range 1-17years). Fourteen cases (18%) received a diagnosis of ACS based on CXR and 21 (26.5%) had ACS discharge diagnosis. Comparing to CXR interpretation as the reference standard, LUS had a sensitivity of 100% (95% CI: 77%-100%), specificity of 68% (95% CI: 56%-79%), positive predictive value of 40% (95% CI: 24%-56%), and negative predictive value of 100% (95% CI: 92%-100%). Overall LUS accuracy was 73.42% (95% CI: 62%-83%). Using discharge diagnosis as the endpoint for both CXR and LUS, LUS had significantly higher sensitivity (100% vs. 62%, p=.0047) and lower specificity (76% vs.100%, p=.0002). LUS also had lower positive (60% vs.100%, p<.0001) and higher negative (100% vs.77%, p=.0025) predictive values. The overall accuracy was similar for both tests (82% vs. 88%, p=.2593). The high negative predictive value, with narrow CIs, makes LUS an excellent ruling-out tool for ACS.

ENLARGED MAIN PULMONARY ARTERY DIAMETER ON COMPUTED TOMOGRAPHY SCAN ASSOCIATED WITH SEVERE RESPIRATORY FAILURE IN PATIENTS WITH ACUTE CHEST SYNDROME

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Enlarged main pulmonary artery diameter (mPAD) on computed tomography (CT) scan is an underutilized screening test for pulmonary hypertension and is especially useful when echocardiographic estimation of pulmonary arterial (PA) pressure is unavailable. Since estimated PA pressure on transthoracic echocardiogram (TTE) is a known risk factor for mortality in sickle cell disease, we examined the relationship between estimated PA systolic pressure on TTE and mPAD on CT scan in patients with sickle cell disease acute chest syndrome to determine whether enlarged mPAD on CT scan was associated with a high-risk phenotype susceptible to severe respiratory failure. METHODS: We retrospectively reviewed all cases of acute chest syndrome treated in the medical intensive care unit (MICU) at two tertiary care hospitals from January 2011 to August 2016 and included all patients with a CT chest before or during their admission. We calculated the Pearson Correlation Coefficient to determine the correlation between mPAD on CT scan and estimated PA systolic pressure on TTE. We compared demographic characteristics in subjects and then used Fisher’s Exact Test to test whether enlarged mPAD on CT scan, defined as >29 mm in men and >27 mm in women, would be associated with respiratory failure requiring non-invasive or mechanical ventilation in patients with acute chest syndrome. RESULTS: Among 83 MICU admissions for acute chest syndrome, 69 (84%) had a CT chest before or during admission and were included as subjects. The correlation (r) between mPAD on CT scan and estimated PA systolic pressure on TTE was 0.59. 37/69 (54%) subjects had an enlarged mPAD, and were more likely to be older (median age 32 versus 26 years, p<0.01) and female (62.2% versus 37.8%, p=0.02). 14 patients with enlarged mPAD developed respiratory failure requiring noninvasive or mechanical ventilation compared to 3 patients with normal mPAD (p=0.03). 6 patients with enlarged mPAD required mechanical ventilation versus 3 without (p=0.49); and 8 with enlarged mPAD required noninvasive ventilation versus 0 without (p<0.01). CONCLUSIONS: There is a moderate correlation between mPAD on CT scan and estimated PA pressure on TTE in patients with acute chest syndrome. Enlarged mPAD on CT scan in patients with acute chest syndrome is associated with increased risk of respiratory failure requiring non-invasive or mechanical ventilation. CLINICAL IMPLICATIONS: Early identification of pulmonary hypertension can affect clinical management of patients with acute chest syndrome. Main pulmonary artery enlargement on CT scan is a useful screening test for pulmonary hypertension and may allow early identification of patients with acute chest syndrome who are at greater risk of severe respiratory failure requiring noninvasive or mechanical ventilation. DISCLOSURES: No relevant relationships by Dhawani Pandya, source=Web Response No relevant relationships by Joseph Simonson, source=Web Response No relevant relationships by Arunabh Talwar, source=Web Response No relevant relationships by Gulrukh Zaidi, source=Web Response

Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa

BackgroundHydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that outweigh treatment-related toxic effects is unknown.MethodsIn a randomized, double-blind trial, we compared hydroxyurea at a fixed dose (approximately 20 mg per kilogram of body weight per day) with dose escalation (approximately 30 mg per kilogram per day). The primary outcome was a hemoglobin level of 9.0 g or more per deciliter or a fetal hemoglobin level of 20% or more after 24 months. Secondary outcomes included the incidences of malaria, vaso-occlusive crises, and serious adverse events.ResultsChildren received hydroxyurea at a fixed dose (94 children; mean [±SD] age, 4.6±1.0 years) or with dose escalation (93 children; mean age, 4.8±0.9 years); the mean doses were 19.2±1.8 mg per kilogram per day and 29.5±3.6 mg per kilogram per day, respectively. The data and safety monitoring board halted the trial when the numbers of clinical events were significantly lower among children receiving escalated dosing than among those receiving a fixed dose. At trial closure, 86% of the children in the dose-escalation group had reached the primary-outcome thresholds, as compared with 37% of the children in the fixed-dose group (P<0.001). Children in the dose-escalation group had fewer sickle cell–related adverse events (incidence rate ratio, 0.43; 95% confidence interval [CI], 0.34 to 0.54), vaso-occlusive pain crises (incidence rate ratio, 0.43; 95% CI, 0.34 to 0.56), cases of acute chest syndrome or pneumonia (incidence rate ratio, 0.27; 95% CI, 0.11 to 0.56), transfusions (incidence rate ratio, 0.30; 95% CI, 0.20 to 0.43), and hospitalizations (incidence rate ratio, 0.21; 95% CI, 0.13 to 0.34). Laboratory-confirmed dose-limiting toxic effects were similar in the two groups, and there were no cases of severe neutropenia or thrombocytopenia.ConclusionsAmong children with sickle cell anemia in sub-Saharan Africa, hydroxyurea with dose escalation had superior clinical efficacy to that of fixed-dose hydroxyurea, with equivalent safety. (Funded by the Doris Duke Charitable Foundation and the Cincinnati Children’s Research Foundation; NOHARM MTD ClinicalTrials.gov number, NCT03128515.)

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

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.

Accuracy of Point-of-care Lung Ultrasonography for Diagnosis of Acute Chest Syndrome in Pediatric Patients with Sickle Cell Disease and Fever.

The objective was to determine the test performance characteristics for point-of-care lung ultrasonography (LUS) performed by pediatric emergency medicine (PEM) physicians compared with radiographic diagnosis of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) and fever. This was a prospective study of patients up to 21 years with SCD and fever requiring chest X-ray (CXR) evaluation for ACS. Before obtaining CXR, a blinded PEM physician performed LUS using a standardized scanning protocol. Positive LUS for ACS was defined as lung consolidation. All patients received CXR and follow-up. The criterion standard for ACS was consolidation on CXR as determined by a blinded radiologist. LUS clips were reviewed by a blinded expert PEM sonologist. A total of 116 febrile events from 91 patients with a median age of 5.7 years were enrolled by 15 PEM sonologists. CXR was positive for ACS in 15 (13%) patients, and LUS was positive for ACS in 19 (16%) patients. Positive LUS had a sensitivity of 87% (95% confidence interval [CI] = 62% to 96%), specificity of 94% (95% CI = 88% to 97%), positive likelihood ratio of 14.6 (95% CI = 6.5 to 32.5), and negative likelihood ratio of 0.14 (95% CI = 0.04 to 0.52) for ACS. The interobserver agreement (kappa) was 0.77. There were two missed cases of ACS on LUS. LUS may be sensitive and specific for diagnosis of ACS in pediatric patients with SCD and fever. LUS may reduce the need for routine CXR and associated ionizing radiation exposure in this population.

Are we missing the mark? Fever, respiratory symptoms, chest radiographs, and acute chest syndrome in sickle cell disease

Are we missing the mark? Fever, respiratory symptoms, chest radiographs, and acute chest syndrome in sickle cell disease

Poor Sensitivity of Physician Assessment to Predict Acute Chest Syndrome in Children with Sickle Cell Disease and Fever

▪Background: Acute chest syndrome (ACS) is a common complication of sickle cell disease (SCD) detected by chest radiography (CXR) with significant morbidity and mortality. Previousstudies show that many children with ACS present without obvious signs or symptoms. We evaluate the sensitivity of clinical assessment for predicting ACS in children with SCD and fever.Methods: This is a prospective cross-sectional, observational study that took place from June 2014-March 2015. Consented providers in 2 CHOA EDs caring for patients aged 0-18 years with SCD and fever 38.0 C completed a questionnaire including vital signs, past history of ACS or asthma, clinical signs, symptoms, physical exam (PE) findings and whether the provider suspected pneumonia/ACS on CXR. CXRs were read by a blinded pediatric radiologist. CXRresults were compared to questionnaire responses completed prior to CXR. Sensitivity, specificity, positive and negative predictive value and accuracy of clinical assessment for predicting ACS compared to CXR was determined. Signs, symptoms, PE findings, and clinical course was compared in cases with positive versus negative CXRs as well as suspected versus unsuspected ACS.Results: 111 SCD fever events with CXR were evaluated over 10 months. Thirteen patients (12%) had evidence of ACS on CXR. Based on MD questionnaires, only 46% of ACS cases were predicted by clinical assessment alone. Physician assessment sensitivity to identify ACS was low at only 50%. (Table 1). An abnormal lung exam, history of ACS, lack of rhinorrhea and a trend towards chest pain were more common in ACS cases compared to children with a negative CXR. However, 62% of children with ACS had a normal lung exam. Cases of unsuspected ACS had a lower degree of fever at presentation to the ED, but ultimately required more packed red blood cell transfusions during hospitalization than suspected ACS cases. There were no other significant differences in signs, symptoms, PE findings or clinical course in suspected vs. unsuspected ACS cases. The recently published NIH guidelines forincluding CXR in a fever work-up for children with SCD (risks include presence of cough, tachypnea, shortness of breath or abnormal lung exam) performed poorly in our cohort, with an Area under the Curve (AUC) = 0.725Conclusions: Clinical impression alone is a poor predictor of ACS in children with SCD and fever. We and others have identified clinical criteria to help identify a high risk group, however many children with ACS lack signs and symptoms of ACS and may be missed based on clinical assessment alone. Given the high mortality and morbidity associated with ACS, empiric CXR may still be indicated in children with SCD. Due to radiation exposure risks with CXR, our team is studying lung ultrasound as an alternative modality for ACS imaging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute Chest Syndrome Rate at the Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System

Background: Acute chest syndrome (ACS) is one of the most feared complications of sickle cell disease. This syndrome is defined by a clinical constellation of symptoms including fever, infiltrate on lung imaging and hypoxia. ACS is a well-known complication to occur early in the hospitalization of patients for sickle cell vaso-occlusive pain crises (VOP). It is hard to differentiate from pneumonia and its rate of occurrence has not been well characterized. Management of ACS includes exchange or simple transfusion, depending on the severity of its presentation, along with critical care support and pain control. Early recognition of this clinical syndrome can lead to better management and outcomes for patients with sickle cell disease.Methods: The Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System has 1073 sickle cell patients and provides a 24/7 acute care unit (ACU) for the evaluation of patients presenting with pain crises. We conducted a retrospective review of all the ACS cases reported at the Center for the last 5 years.Results: The number of sickle cell patient-visits in the ACC was 4409. 30 cases of ACS were confirmed on retrospective review. The rate of ACS was 6.8 per 1000 patient visits. The median age was 39, and the patients' phenotypes 89% SS and 11% SC. Of the patients evaluated, 18% were smokers, 43% were taking hydroxyurea and 89% were taking folic acid. Seventy five percent of the patients were successfully managed with supportive care only, while the remaining 25% required red cell exchanges. On admission, the median white cell count (WBC), platelet count, LDH and reticulocyte count were increased above their upper limits of normal. Eighteen percent of the patients had a d-dimer checked and the median was well above the range of normal (6097). Table 1 shows the patient characteristics and data.Discussion: The rate of ACS over the last 5 years at our sickle cell center is well below historic reports of ACS. We believe that several factors explain our observation. Because our 24/7 ACU is staffed with providers who know their patients' histories and treatment plans and are experienced in the management of VOP, we postulate that our comprehensive management approach involving the rapid and appropriate initiation of intravenous fluids, the administration of pain medications along with antibiotics, and the use of anti-inflammatory medications contribute to the truncation of the sickle cell-related inflammatory state and the prevention of serious complications such as ACS. The fact that inflammatory markers (WBC, Platelet count, LDH) were initially elevated is to be expected in the setting of VOP. What is remarkable is the high percentage of good patient outcomes associated with our comprehensive management approach. This retrospective report should be validated in a prospective study that compares the results of the management of all acute care VOP visits delivered in a 24/7 ACU with the management of acute care VOP delivered in a general emergency room. Such a study should include the collection of laboratory and clinical data that is typically abnormal in patients with VOP. If a significantly decreased rate of ACS rate is observed when 24/7 ACU care is provided, then the institution of 24/7 acute care units would be warranted on a national level to improve the survival of patients with sickle cell disease.Table 1Characteristics of patients studiedAge median (range)39 (19-58)GenderFemales 14/ males 14Genotype n (%)SC 3 (11%)/ SS 25 (89%)Smoking (%)18 %Hydrea use (%)43%Folic acid use (%)89%Management n (%)Exchanged 7 (25%)/ supportive 21 (75%)Hemoglobin median (range)10.4 (4.9-11.1)White count median (range)18.6 (6.1-47)Platelet median (range)492 (79-646)Reticuolcyte count median (range)300.6 (151-597)LDH median (range)677 (238-2287)D-dimer % patients/ median (range)18%/ 6097 (609-33370)Ferritin % patients/ median (range)11%/ 2844 (335.2-6060)Total/direct bilirubin median (range)3.7/1.3 (1-19/0.2-4.9)Creatinine median (range)1.3 (0.5-3.5)AST/ALT median (range)59/49 (21-110/12-118) DisclosuresNo relevant conflicts of interest to declare.

The Acute Chest Syndrome in Cameroonian children living with sickle cell disease.

BackgroundAlthough sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country.MethodsThis was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization.ResultsTwenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9 % with a mean of 14.6 % (6.0 %). The three main symptoms at admission were fever (90.5 %), cough (81 %) and chest pains (28.6 %). Two patients (9.5 %) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm3, 23476 (11543.7)/mm3, 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5 %). Treatment associated broad-spectrum antibiotics (100 %), hydration (100 %), analgesics (43.2 %), whole blood transfusion (66.7 %), and oxygen supplementation (33.3 %). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05).ConclusionACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients’ parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.

Spinal versus general anesthesia for Cesarean section in patients with sickle cell anemia.

BackgroundSickle cell anemia (SCA) increases the rate of maternal and fetal complications. This pilot study was designed to compare the maternal and fetal outcomes of spinal versus general anesthesia (GA) for parturients with SCA undergoing cesarean delivery.MethodsForty parturients with known SCA scheduled for elective Cesarean delivery were randomized into spinal anesthesia (n = 20) and GA groups (n = 20). Perioperative hemodynamic parameters were recorded. Postpartum complications were followed up. Opioid consumption was calculated. Blood loss during surgery and the number of patients who received intraoperative or postpartum blood transfusion were recorded. Patient satisfaction with the type of anesthesia was assessed. The Apgar score at 1 and 5 min, neonatal admission to the intensive care unit, and mortality were also recorded.ResultsBlood loss was significantly higher in the GA than spinal group (P = 0.01). However, the number of patients who received an intraoperative or postpartum blood transfusion was statistically insignificant. Significantly more patients developed intraoperative hypotension and bradycardia in the spinal than GA group. Opioid use during the first 24 h was significantly higher in the GA than spinal group (P < 0.0001). More patients had vaso-occlusive crisis in the GA than spinal group without statistical significance (P = 0.4). There was one case of acute chest syndrome in the GA group. No significant differences were observed in postoperative nausea and/or vomiting, patient satisfaction, or hospital length of stay. Neonatal Apgar scores were significantly better in the spinal than GA group at 1 and 5 min (P = 0.006 and P = 0.009, respectively). Neonatal intensive care admission was not significantly different between the two groups, and there was no neonatal mortality.ConclusionsSpinal anesthesia may have advantages over GA in parturients with SCA undergoing Cesarean delivery.

Detection of Pulmonary Platelet Thrombi in Acute Chest Syndrome in Sickle Cell Disease: Novel Findings in an Autopsy Case Series

Introduction: Acute chest syndrome (ACS) is one of the leading causes of death in patients with sickle cell disease (SCD). The pulmonary manifestations of ACS often appear suddenly and can progress rapidly to fatality. There are multiple identified etiologies associated with the development of ACS including infection, fat or pulmonary embolism, and opiate intoxication. The cause cannot be attributed to a single agent in most cases and if so, is likely determined authoritatively only at autopsy. One potential commonality, however, is that an acute pain event usually precedes the onset of ACS. Although, clearly there remains much to be learned, acute pain events are one of the better characterized aspects of SCD. In most cases, there is an increase in inflammatory markers and indicators of endothelial dysfunction. Platelet activation increases during pain events, as do platelet-derived markers of inflammation. In fact, platelets are emerging as potentially pivotal contributors to the overall inflammatory state of patients. Although patients at steady state typically have high platelet counts, platelet count decrease during pain events. Overt thrombocytopenia has been noted in ACS and is usually attributed to platelet sequestration in the vasculature. Thus, we considered the platelet to be a potential contributor to pulmonary pathology in cases of ACS. To lend support to our hypothesis, we performed an autopsy study of pulmonary histology in patients with SCD and ACS.Objective: To interrogate whether platelet thrombi were significant findings in lungs of patients who died concurrent with ACS.Methods: We performed an autopsy case series. Ten autopsies and corresponding medical records from patients with SCD were selected from those conducted at Georgia Regents Medical Center from 1997-2013. From the medical record or autopsy report, all cases had ACS listed concurrent with or as the primary cause of death. No pediatric cases were included in the series (age range 18-45 years old). Paraffin-embedded lung samples were obtained from all cases. Standard immunohistochemical techniques were used to detect platelet thrombi. A comprehensive perimortem medical record was available for 8 patients. A genotype of either SS or S/β0-Thalassemia was acceptable. Two cases were recorded with an S/β0-Thalassemia genotype, the rest were listed as SS.Results: Profound arterial platelet thrombi were detected in 3 out of the 10 cases. In these 3 positive cases, arterial vessels of all size (large arterial vessels to arterioles) were completely occluded by platelets. All platelet positive cases had a genotype of SS. In 2 of the 3 platelet thrombi positive cases, none of the established causes of ACS were noted in the medical record or autopsy report. In 1 platelet positive case, lipid-laden macrophages and ascites were noted at autopsy. Extensive pulmonary artery remodeling was noted in all 10 cases regardless of age or medical history.Conclusions: This case series illustrates that platelet- rich arterial thrombi are present in potentially up to 33 percent of fatal cases of ACS. These data are thus suggestive of a novel pathological role for platelets in ACS. DisclosuresKutlar:NIH/NIMHD: Research Funding.

An Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia

▪ IntroductionVaso-occlusive crisis (VOC) is the hallmark of sickle cell anemia (SCA), yet VOC treatment has not improved in decades. Recently the role of adhesive interactions between leukocytes, erythrocytes, and the vascular endothelium has been recognized in VOC. GMI 1070, a pan-selectin inhibitor, was designed to decrease the contribution of leukocyte adhesion to VOC. Herein, we report a sub-analysis of the pediatric patients enrolled in a study of GMI 1070 with the aims of determining the efficacy and toxicities in this subgroup and comparing pediatric to adult patients. MethodsThis multi-center, randomized, double-blind, placebo-controlled phase 2 trial enrolled afebrile patients ≥ 12 yrs with HbSS or HbSβ0 thalassemia presenting with VOC. Subjects had no organ dysfunction or other acute SCA complications. GMI 1070 was administered IV as a loading dose, then in up to 14 q12 h maintenance doses. Following a pre-specified interim PK analysis including 1 pediatric and 10 adult subjects, the loading and maintenance doses were doubled. Other management was at the discretion of the treating physician. Pain intensity was measured with a 10 cm visual analog scale. The primary outcome was time to resolution of VOC, defined as either a sustained 1.5 cm decrease in the pain score and cessation of IV analgesics; readiness for discharge; or hospital discharge. Secondary outcomes included time to discharge, time to transition from IV to oral analgesics, opioid usage, and safety profile. Median time-to-event was compared between arms using the Kaplan-Meier (KM) method. Analysis of covariance was used to compare the mean hourly opioid use, by hospital day. ResultsSeven sites enrolled 20 pediatric subjects: GMI 1070 - 13 vs placebo - 7. The median age was 14 years, and 40% were female. Time to 1st dose of study drug was a mean of 15 h from initial medical evaluation. Median length of stay was 105 h. The GMI 1070 arm had a 60.7 h reduction in the median time to resolution of VOC compared to placebo (Fig. 1a). Similarly, the median difference in time to transition to oral opioids and time to discharge were clinically significant between GMI 1070 and placebo at 87.8 h and 96 h, respectively (Fig. 1b & 1c). Mean hourly opioid use was lower with GMI 1070 than placebo in the first 24 h, but the trajectory thereafter did not differ (Fig. 1d). The effect of GMI 1070 on the primary and secondary outcomes was similar for pediatric and adult subjects (Table 1). Differences between pediatric and adult subjects included which opioid was used (pediatrics – 80% morphine vs adults – 80% hydromorphone). Also more pediatric subjects received IV antibiotics (Table 1), particularly in the first 24 hrs of study drug (pediatrics – 35% vs adults – 14%).The proportion of pediatric subjects experiencing a serious adverse event (SAE) was similar between arms (GMI 1070 – 31% vs placebo – 43%). Most SAE's were VOC recurrence; 1 SAE was an episode of acute chest syndrome (ACS) in the GMI 1070 arm (0 in the placebo arm). Of 4 total ACS events (1 SAE, 3 AE), 3 occurred within 24 h of 1st study drug, 1 required red blood cell transfusion and 0 required intensive care. No severe or unusual infections occurred in either arm. [Display omitted] ConclusionsGMI 1070 is a promising agent for reducing duration of VOC in SCA. Compared to adults, pediatric subjects demonstrated similar efficacy and safety. The ACS cases in the GMI 1070 arm are noteworthy but are not definitively associated with study drug. The strong efficacy signal in adolescents, along with minimal safety concerns, warrants inclusion of younger children in a subsequent phase 3 clinical trial of GMI 1070. [Display omitted] Disclosures:McCavit:Pfizer, Inc.: Consultancy; GlycoMimetics, Inc.: Research Funding. Krishnamurti:GlycoMimetics, Inc.: Research Funding. Hsu:GlycoMimetics, Inc.: Research Funding. Quinn:Glycomimetics: Research Funding; Eli Lilly: Research Funding; MAST Therapeutics: Research Funding; American Society of Hematology: Advisory Committees, Advisory Committees Other, Honoraria. Odame:Glycomimetics: Research Funding. Alvarez:Glycomimetics: Research Funding. Driscoll:Glycomimetics: Research Funding. Smith-Whitley:GlycoMimetics, Inc: Research Funding. Rhee:Rho, Inc.: Employment; GlycoMimetics, Inc.: Research Funding. Wun:Emmaus, Inc.: Clinical Adjudication Committee Other; Pfizer, Inc.: Consultancy; GlycoMimetics: Research Funding. Telen:GlycoMimetics, Inc.: Research Funding; Dilaforette, NA: Research Funding; Pfizer, Inc.: Consultancy. Thackray:GlycoMimetics, Inc.: Employment, Equity Ownership.

Preoperative Transfusion Practices and Outcomes in Sickle Cell Patients Admitted to California Hospitals,

Abstract 4189 Introduction:Surgery in patients with Sickle Cell Disease (SCD) is associated with a high rate of postoperative complications, including acute chest syndrome (ACS). Some early reports have suggested that the overall complication rate may be as high as 50% and the mortality rate 10%. In 1995, a large multicenter trial conducted at SCD centers in the U.S. showed that preoperative transfusion reduced complications related to sickling. Despite transfusions, 10% of the patients in this study developed ACS. Recently, smaller studies in the US and other countries have suggested that not all SCD patients who undergo surgery need a transfusion. Practices may vary depending on surgical risk and the clinical history of the patient. For example, while most SCD centers use preoperative transfusions, practices outside of centers (where the majority of patients are being followed) are not well understood. To describe the transfusion practices in our state as well some of the outcomes of SCD patients who undergo surgery, we queried California's statewide hospital discharge database to describe the frequency of preoperative transfusions for SCD patients as well as the frequency of ACS following surgery. Methods:This was a retrospective cohort study using 2005–2008 public data from the California Office of Statewide Health Planning and Development (OSHPD). Data included all inpatient discharges from all non-federal California hospitals. Inclusion criteria included the presence of a sickle cell disease ICD-9 code in the primary or a secondary diagnosis (282.60–282.69, 282.41–282.42) and the presence of ICD-9 codes for one of the six most common surgical procedures performed in SCD: tonsillectomy, cholecystectomy, splenectomy, hysterectomy, therapeutic abortion, and hip arthroplasty. A variable summarizing the temporal sequence of transfusion and surgery was created by comparing the number of days to surgery with the number of days to transfusion. Cases were coded for the presence of ACS (517.3) or respiratory diagnoses (including pneumonia, pulmonary edema, acute respiratory distress syndrome, hypoxia and respiratory failure) in any primary or secondary diagnosis. Transfusion, ACS diagnosis, and mortality frequencies were described, and differences in outcome between patients treated with or without transfusion were assessed with chi-square tests. Results:Between 2005 and 2008, 468 visits to California hospitals by patients with SCD were associated with one of the six targeted surgical procedures. Of these visits, 222 cases (47.4%) were associated with a transfusion. Of the 179 cases in which the timing of transfusion could be determined, 145 visits (81%) were associated with a preoperative transfusion, and 34 visits (19%) were associated with a transfusion given after surgery. ACS was documented in 59 (12.6%) surgical patients. Forty three cases of ACS occurred in the transfused patients(19%). Sixteen cases(6.5%) occurred in the non transfused group. The timing of transfusion was available in 32 of the ACS cases, of which 21 had a transfusion either before or on the same day of surgery and 11 were transfused after surgery. There were four deaths in the cohort: three patients had been transfused and developed ACS.The fourth patient was never transfused and did not develop ACS. Conclusions:Over half of the SCD patients in California are not transfused in association with a surgical procedure. The majority of transfused patients received preoperative transfusions and were more likely to develop ACS or a related pulmonary complication following surgery, whereas the frequency of ACS was lower in the nontransfused group. This latter finding could be consistent with a group of patients with less severe disease. Similarly, the increased frequency of death in transfused patients likely reflects the clinical severity of this group. Although we were unable to determine if preoperative transfusions were administered prior to hospital admission, the data suggests that many patients are not being given what many sickle cell providers in the US consider standard preoperative treatment. Finally, the frequency of ACS in transfused patients was nearly twice that of the study performed in academic sickle cell centers in 1995. This finding is consistent with the notion that many California patients do not receive care at a sickle cell center and thus may have poorer outcomes Disclosures:No relevant conflicts of interest to declare.

Acute chest syndrome is associated with history of asthma in hemoglobin SC disease

Acute chest syndrome (ACS) is a frequent cause of morbidity and leading cause of death among individuals with sickle cell disease. Yet, ACS in hemoglobin SC disease is not well characterized. The objective of this study was to compare the presentation and clinical course of ACS in individuals with hemoglobin SC disease to that observed in individuals with hemoglobin SS disease. We retrospectively reviewed 71 inpatient episodes of ACS in patients with hemoglobin SC disease over a 20-year period. Continuous and categorical data from index cases were compared with that from 71 control cases of ACS in patients with hemoglobin SS disease. Median length of hospitalization was shorter for hemoglobin SC episodes when compared to hemoglobin SS episodes (3.0 vs. 5.0 days, P < 0.001). In comparison to hemoglobin SS patients, a greater proportion of hemoglobin SC patients had a previous history of asthma or wheezing (50.7 vs. 33.8%, OR = 2.01 [1.02-3.96], P = 0.041) and a respiratory complaint of wheeze (11.3 vs. 2.8%, OR = 4.38 [0.90-21.4], P = 0.049). In our multivariate regression model, time to ACS diagnosis and total number of days of oxygen supplementation were independent predictors of length of hospitalization in both hemoglobin SC and SS episodes of ACS. ACS appears to be less severe in children with hemoglobin SC disease compared to that in children with SS disease. Asthma and wheezing may represent more significant risk factors for the development of ACS in children with hemoglobin SC disease.

Use of Transfusion to Treat Acute Chest In Sickle Cell Disease:California Hospital Practice Patterns

AbstractAbstract 253 Introduction:Acute chest syndrome (ACS) is a leading cause of morbidity and mortality in patients with Sickle Cell Disease (SCD). Although the NIH recommends transfusion as standard of care therapy for this diagnosis, practice patterns vary. In 2000, the National Acute Chest Study group found that 72% of patients with ACS were transfused. This study, which was perfomed at academic medical centers with sickle cell treatment programs, used specific diagnostic inclusion criteria. As ACS may be difficult to distinguish from pneumonia, recognition and treatment of the diagnosis may vary by hospital and by presence or absence of a sickle cell specialist. With access to hospital discharge data from all California hospitals seeing SCD patients, we aimed to describe transfusion practices in ACS. Methods:This retrospective cohort study uses 2005–2008 public data from the California Office of Statewide Health Planning and Development (OSHPD). Data included all inpatient and emergency department (ED) discharges from all non-federal California hospitals. Cases were selected based on discharge from or admission via an ED and the presence of a sickle cell disease ICD-9 code in the primary or a secondary diagnosis (282.60-282.69, 282.41–282.42). Further inclusion criteria included presence of ACS (517.3) or respiratory diagnoses including pneumonia, pulmonary edema, acute respiratory distress syndrome, hypoxia and respiratory failure in any primary or secondary diagnosis. Frequency of transfusion, intubation and mortality were described and chi-square tests were performed to determine the statistical significance of differences between groups of patients treated with or without transfusion as well as between groups of adults and children. Results:Between 2005–2008, 4306 ED visits by Californians with SCD were associated with either ACS or a related respiratory diagnosis and only 42.5% of these cases were associated with transfusion. Limiting the diagnosis to ACS only, 1399 cases were identified, and still only 50.4% of these cases were associated with transfusion. Among patients with ACS or a related diagnosis, the majority were admitted to the hospital (90.9%); only 59.2% of intubated cases (n=238) were transfused; and of the 92 deaths during this period, only 46.7% were associated with transfusion. Patients who were 18 and over were transfused more often than young children (43.2% vs. 35.7%; 2(1)=12.37, p<0.001). Conclusions:Despite transfusion being the standard of care for treatment of ACS as well as other sickle–related complications, many ACS cases in California are not being treated in this manner. Surprisingly, the most severely ill patients, those who were either intubated or died during the study period, had a lower transfusion frequency than the cohort as a whole. Although some mild pediatric cases may not be transfused, a minority of the total cohort was under 18 years old. Recent studies imply that patients transitioning out of pediatric SCD programs have an increased risk of dying due to ACS and other serious SCD complications. Our study suggests that underutilization of transfusion may play a role in these poor adult outcomes in SCD. These findings prompt further investigation into the role of transition to adult care and appropriate medical homes in access to quality SCD care. Disclosures:No relevant conflicts of interest to declare.

Syndrome thoracique aigu associé à une infection àBordetella bronchiseptica chez un enfant drépanocytaire

We describe a case of acute chest syndrome associated with Bordetella bronchiseptica pneumonia in a child with sickle cell disease. B. bronchiseptica is recognized as an important pathogen of the respiratory tract for a large variety of animal species. This zoonotic agent has been frequently associated with chronic and recurrent infections. In humans, the bacterium acts as an opportunistic pathogen affecting mostly immunocompromised patients or those with preexisting respiratory diseases. This case and literature review provides an opportunity to discuss the risk factors, treatment, follow-up, and prevention of such zoonotic infections in the context of a lack of cross-protection of new pertussis vaccines.

Acute chest syndrome in sickle cell disease

Acute chest syndrome is a common cause of death among patients with sickle cell disease, and an unfamiliar condition to most Australian medical practitioners. We present a case of acute chest syndrome successfully treated with inhaled nitric oxide and exchange transfusion. In the discussion we review current and future management options of acute chest syndrome.