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Background: Acute Chest Syndrome (ACS) is the leading cause of death in children with sickle cell disease (SCD) in the US-about half of the children who develop ACS present initially with pain., Methods: Here, we studied biomarkers to differentiate ACS from vaso-occlusive crises (VOC) in children with SCD who presented with pain to the emergency department (ED). We conducted a prospective cohort study of consecutive patients who presented to the ED with pain and were discharged with ACS or VOC between March, 2017 and February, 2020., Results: We identified 7 patients with ACS and 19 patients with VOC. The two groups were comparable in age and sex. All patients with ACS had asthma versus 42% of the VOC group. The ACS group had lower weight and BMI z-scores. Patients with ACS compared to VOC had significantly higher respiratory rates, lower O 2 saturation, and longer hospital stays. They also had higher white blood cell count, glucose level (> 99 mg/dL), anion gap (> 9 mEq/L), sPLA2 (> 7 pg/mL), IFN-γ (> 17.8 pg/mL), IL-10 (1.54 pg/mL), and IL-12 (> 0.5 pg/mL) levels., Conclusions: We identified biomarkers associated with ACS development in children with SCD presenting with pain that allow for earlier ACS interventions to reduce mortality and morbidity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS., Study Design and Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they had to rate. The survey also included three case scenarios to assess physician attitudes about the management of ACS. Management options included supportive and preventive strategies in addition to transfusion therapy options., Results: Out of 455 physicians who received the survey, 195 responded (response rate = 43%). The respondents were primarily hematology/oncology physicians. The responses showed wide variability among physicians in how diagnostic criteria for ACS are used and how physicians risk-stratify ACS patients in their practice. The responses also reflected variability in the use of transfusions for ACS., Discussion: Based on our results, we conclude that ACS is diagnosed and managed inconsistently among expert physicians, especially in their transfusion practices due to a lack of consensus on risk stratification criteria. Our data suggest an urgent need for well-designed prospective studies to provide evidence-based guidelines and minimize management variability among physicians who care for individuals with SCD and ACS., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Acute chest syndrome (ACS) is a leading cause of respiratory distress and hospitalisation in children with sickle cell disease (SCD). The aetiology is multifactorial and includes fat embolism, venous thromboembolism, alveolar hypoventilation and respiratory infections, with the latter being particularly common in children. These triggers contribute to a vicious cycle of erythrocyte sickling, adhesion to the endothelium, haemolysis, vaso-occlusion and ventilation-perfusion mismatch in the lungs, resulting in the clinical manifestations of ACS. The clinical presentation includes fever, chest pain, dyspnoea, cough, wheeze and hypoxia, accompanied by a new pulmonary infiltrate on chest radiography. Respiratory symptoms may overlap with those of acute asthma, which may be difficult to distinguish. Patients with ACS may deteriorate rapidly; thus prevention, early recognition and aggressive, multidisciplinary team management is essential. In this narrative review, we highlight the current evidence regarding the epidemiology, pathophysiology, treatment and preventative strategies for ACS, focusing on the aspects of major interest for the paediatric pulmonologist and multidisciplinary team who manage children with SCD., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Abstract: Sickle cell disease (SCD) is an autosomal recessive disorder altering the shape of red blood cells, causing harmful obstructions in blood vessels, therefore altering normal blood flow. SCD can escalate quickly into acute chest syndrome (ACS), a life-threatening complication that requires immediate care. This article discusses the pathophysiology, assessment, diagnosis, and treatment of ACS, as well as nursing care and patient education., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Acute chest syndrome (ACS) in sickle cell disease (SCD) is a serious condition that carries with it a high rate of morbidity and mortality., Objective: This review highlights the pearls and pitfalls of ACS in SCD, including diagnosis and management in the emergency department (ED) based on current evidence., Discussion: ACS is defined by respiratory symptoms and/or fever and a new radiodensity on chest imaging in a patient with SCD. There are a variety of inciting causes, including infectious and non-infectious etiologies. Although ACS is more common in those with homozygous SCD, clinicians should consider ACS in all SCD patients, as ACS is a leading cause of death in SCD. Patients typically present with or develop respiratory symptoms including fever, cough, chest pain, and shortness of breath, which can progress to respiratory failure requiring mechanical ventilation in 20% of adult patients. However, the initial presentation can vary. While the first line imaging modality is classically chest radiograph, lung ultrasound has demonstrated promise. Further imaging to include computed tomography may be necessary. Management focuses on analgesia, oxygen supplementation, incentive spirometry, bronchodilators, rehydration, antibiotics, consideration for transfusion, and specialist consultation. Empiric antibiotics that cover atypical pathogens are necessary along with measures to increase oxygen-carrying capacity in those with hypoxemia such as simple transfusion or exchange transfusion., Conclusions: An understanding of ACS can assist emergency clinicians in diagnosing and managing this potentially deadly disease., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)

Sickle cell disease is a frequent genetic condition, due to a mutation of the β-globin gene, leading to the production of an abnormal S hemoglobin and characterized by multiple vaso-occlusive events. The acute chest syndrome is a severe complication associated with a significant disability and mortality. It is defined by the association of one or more clinical respiratory manifestations and a new infiltrate on lung imaging. Its pathophysiology is complex and implies vaso-occlusive phenomena (pulmonary vascular thrombosis, fat embolism), infection, and alveolar hypoventilation. S/S or S/β 0 -thalassemia genotype, a history of vaso-occlusive crisis or acute chest syndrome, a low F hemoglobin level (<5%), a high steady-state hemoglobin level (> 10 g/dL), or a high steady-state leukocytosis (>10 G/L) are the main risk factors. Febrile chest pain, dyspnea, sometimes cough with expectorations are its main clinical manifestations, and bi-basal crackles are found at auscultation. Inferior alveolar opacities with or without pleural effusions are identified on chest X-ray or CT-scan. Management of the acute chest syndrome should be prompt and implies, besides the recognition of severity signs, a multimodal analgesia, oxygen supplementation, sometimes a parenteral antibiotic treatment and the frequent use of blood transfusions especially in the most severe cases. Prevention is important and includes a regular monitoring of hospitalized patients and the use of incentive spirometry., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications., Methods: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed., Results: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%., Conclusions: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established., Areas Covered: To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed., Expert Opinion: 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.

We showed in the present study that, not unlike in adult patients with sickle cell disease (SCD), Townes mice exhibit increases in serum intestinal fatty acid binding proteins and lipopolysaccharides (LPS), together with a breach in the intestinal barrier. These abnormalities increased rapidly after the induction of vaso-occlusive crisis (VOC). We also confirmed higher intestinal microbial density in SCD. These findings support the concept that SCD and/or its complications, and not hospitalisation or medications, are responsible for the intestinal pathophysiological changes. The present results provide the basis for use of Townes mice to further elucidate the mechanistic relationship between intestinal pathophysiology and VOC., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Children with sickle cell disease (SCD) frequently present to hospital acutely unwell and are often exposed to diagnostic chest X-rays (CXRs). Little evidence exists to determine when CXRs are clinically useful. Using electronic hospital records, we audited CXR use in children aged 0-18 who presented to hospital over the past 10 years in both an inpatient and emergency department setting. From a total of 915 first CXRs, only 28·2% of CXRs (n = 258) had clinically significant findings that altered management or final diagnosis. Of these abnormalities, consolidation represented 52·3%, effusion 8·9%, cardiomegaly 8·4% and sickle cell-related bone changes 6·3%. Indications for CXR of respiratory distress (OR = 3·74, 95% CI 2·28-6·13), hypoxia (OR = 1·86, 95% CI 1·50-2·31) and cough (OR = 1·64, 95% CI 1·33-2·02), were more likely to have significant CXR findings. Patients who had higher peak fever (38·4°C vs. 37·4°C, P = 0·001), higher peak CRP (156·4 vs. 46·1, P < 0·001) and higher WCC (20·2 vs. 13·6, P < 0·001) were more likely to have clinically significant abnormalities on CXR. We found a decision tool using either hypoxia, cough, respiratory distress, T > 38°C, CRP > 50 or WCC > 15 × 10 9 /l as indications for CXR, to have a sensitivity of 88% (with 95% CI 0·78-0·95) and specificity of 46% (95% CI 0·43-0·50) for clinically significant findings., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Sickle cell disease (SCD) is an inflammatory disease that can result in both chronic and acute inflammation. Immature granulocytes (IG) are not-yet-mature white blood cells that can be easily detected in complete blood count (CBC) tests. In recent studies it has been suggested that IG may play a role in determining the prognosis of inflammatory diseases. The aim of our study was to investigate the role of IG percentage on predicting acute chest syndrome (ACS) and the severity of vaso-occlusive crisis (VOC) in patients with SCD., Methods: The study cohort consisted of 49 SCD patients admitted to the emergency department for VOC. If symptoms did not regress despite appropriate treatment including hydration and analgesia, they were hospitalized. Patients whose symptoms regressed were discharged from the emergency department within 24 hours. Blood samples, including CBC and C-reactive protein (CRP), a marker of inflammation, were taken within the first hour of admission. Steady state laboratory parameters from the previous visit in the last three months were collected from patient files., Results: The mean age was 18±4 (range 8-25) years. Most were hospitalized (41/49; 83.7%) and 8 of 49 were discharged from the emergency department after their treatment for VOC. ACS developed in 13 of 49 (26.5%). White blood cell, neutrophil and nucleated red blood cell counts, percentage of IG (IG%) and CRP levels were significantly increased in patients with VOC. IG% of patients with ACS was significantly higher than patients without ACS. However, ROC analysis showed that IG% was not associated with the development of ACS or hospitalization for VOC., Conclusions: Despite a small SCD cohort, the significant increase in the IG% in patients with VOC compared to their baseline values has suggested a role for IG% in predicting VOC. Although IG% was higher in ACS, its utility in predicting ACS was poor.

Acute chest syndrome (ACS) is a common cause of death for sickle cell disease patients. This syndrome is defined as: respiratory symptoms, new X-ray findings developed and/or fever; ACS requires prompt treatment to avoid clinical deterioration and death in adults with sickle cell disease. Sixteen episodes of acute chest syndrome were studied in 16 adults with sickle cell disease. The clinical and radiological findings, treatment, response and outcome of the episode were evaluated respectively. The patient's past history and comorbidities were taken into account in the outcome and days of hospitalization. Fourteen patients recovered with no sequelae; one patient who required mechanical ventilation also recovered; one patient died due to pulmonary emboli. The mean hospitalization days were 7.43.

Introduction: the spectrum of pulmonary complications in sickle cell anemia (SCA) comprises mainly of acute chest syndrome (ACS), pulmonary hypertension (PH) and airway hyper-responsiveness (AHR). This study was conducted to examine the abnormalities in pulmonary function tests (PFTs) seen in children with SCA., Methods: electronic databases (Cochrane library, PubMed, EMBASE, Scopus, Web of Science) were used as data sources. Two authors independently reviewed studies. All case-control studies with PFT performed in patients with SCA and normal controls were reviewed. Pulmonary functions were assessed with the help of spirometry, lung volume and gas diffusion findings., Results: nine studies with 788 SCA children and 1101 controls were analyzed. For all studies, the pooled mean difference for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow rate (PEFR), total lung capacity (TLC) and carbon mono-oxide diffusing capacity (DLCO) were -12.67, (95% CI: -15.41,-9.94), -11.69, (95% CI: -14.24, -9.14), -1.90, (95% CI: -4.32, 0.52), -3.36 (95% CI: -6.69, -0.02), -7.35, (95% CI: -14.97, -0.27) and -4.68, (95% CI -20.64, -11.29) respectively. FEV1 and FVC and were the only parameters found to be significantly decreased., Conclusion: sickle cell anemia was associated with lower FEV1 and FVC, thus, supporting the role of routine monitoring for the progression of lung function decline in children with SCA with ACS. We recommend routine screening and lung function monitoring for early recognition of pulmonary function decline., Competing Interests: The authors declare no competing interests., (Copyright: Amar Taksande et al.)

Background: Small cell-derived extracellular vesicles (EVs) can affect endothelial function. We previously found that patients with sickle cell disease (SCD) have greater numbers of circulating EVs than subjects without the disease, and the EVs differentially disrupt endothelial integrity in vitro. Because endothelial disruption is a critical component of acute chest syndrome (ACS), we hypothesized that EVs isolated during ACS would induce greater endothelial damage than those isolated at baseline., Methods: Nine pediatric subjects had plasma isolated at baseline and during ACS from which EVs were isolated. Cultured microvascular endothelial cells were treated with EVs and then studied by immunofluorescence microscopy to localize VE-cadherin and F-actin., Results: The EVs had a diameter of 95 nm. They contained CD63 and flotillin-1, which were increased in SCD patients (5-13-fold compared to control) and further increased between baseline and ACS (24-57%). The EVs contained hemoglobin, glycophorin A, and ferritin. Treatment with baseline EVs caused modest separation of endothelial cells, while ACS EVs caused substantial disruptions of the endothelial cell monolayers. EVs from subjects with ACS also caused a 50% decrease in protein levels of VE-cadherin., Conclusions: These results suggest that circulating EVs can modulate endothelial integrity contributing to the development of ACS in SCD patients by altering cadherin-containing intercellular junctions., Impact: Sickle cell disease patients have circulating extracellular vesicles (EVs) that modulate endothelial integrity by altering cadherin-containing intercellular junctions. Disruption is more severe by EVs obtained during acute chest syndrome (ACS). These results expand our knowledge of the pathophysiology of acute chest syndrome and the vasculopathies of sickle cell disease.

Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae ( Spn )-a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H 2 O 2 ) as a virulence strategy. Apart from H 2 O 2 , Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.

New York City has emerged as one of the epicenters of the SARS-COV-2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS-COV-2-positive patients admitted with ACS. SARS-COV-2-positive SCD patients, who did not develop ACS, were the comparison group. Hydroxyurea use (P-value = .02) and lower absolute monocyte counts (P-value = .04) were noted in patients who did not develop ACS. These preliminary findings need to be further evaluated in larger cohorts., (© 2020 Wiley Periodicals LLC.)

Objectives: In this study, we investigated the evolution of chronic pain in sickle cell patients (SCD) as an age-dependent phenomenon and studied the frequency of vaso-occlusive episode frequency, opioid use, quantitative sensory testing (QST), and biomarkers of chronic pain (CP)., Methods: We undertook a cross-sectional study of the evolution of CP in SCD. A total of 72 subjects (age 15-66) were enrolled. VOE frequency, presence of CP hydroxyurea (HU) therapy, opioid use, and laboratory parameters were collected. QST was performed, and plasma tryptase, substance P, and NGF (Nerve Growth Factor) levels were assayed., Results: There was an age-dependent increase in frequency of CP, VOEs, opioid use, and Von Frey monofilament values. CP patients had significantly higher opioid use (daily morphine equivalents) (52.8 mg vs 6.94 mg, P = .009), suggesting a correlation between opioid use and hyperalgesia. NGF levels were also significantly higher (P = .051). Our results confirm previous observations of an age-dependent increase in the proportion of patients with CP and support the contributing role of mast cell activation and neurogenic inflammation., Conclusions: This is the first study of NGF as a possible biomarker of CP in SCD. If confirmed, this could provide a diagnostic marker and therapeutic target for CP in SCD., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Asthma is associated with increased rate of acute chest syndrome (ACS), pain episodes and premature death. Differentiating between an acute asthma exacerbation and ACS is a challenge clinically as they can present with similar symptoms. Clinicians should be aware of symptoms of asthma or broncho spasm in any children with sickle cell disease, as adequate treatments are required. In this mini-review, we selected 16 clinical studies, published in English between 2004 and 2016, and reviewed all of the abstracts and references of the selected articles. We subsequently selected articles that were focused on asthma in children with sickle cell disease. Given the pathophysiological mechanisms of ACS and the association between asthma and sickle cell disease, the management approach of asthmatic children should be clarified. Bronchodilators should be used if there are clinical features suggestive of a history of asthma or evidence of acute broncho spasm. The indication for cortisone should be reassessed. This literature review failed to conclude on therapeutic modalities of ACS in asthmatic children with sickle cell disease. Only a well designed, multicenter adequately-powered randomized controlled study of each of them will allow assessing their real benefits and risks.

Study Objective: Acute chest syndrome is a leading cause of mortality in patients with sickle cell disease (SCD). Because early detection of acute chest syndrome is directly tied to prognosis, young patients with SCD undergo countless chest radiography screenings throughout their lifetime for commonly occurring acute chest syndrome risk factors such as fever, chest pain, or cough. Chest radiography is not an ideal screening method because it is associated with radiation exposure, which accumulates with repeated imaging. Point-of-care lung ultrasonography is a nonradiating imaging modality that has been used to identify other lung pathology and may have a role in SCD. The goal of this study was to determine the accuracy of point-of-care lung ultrasound to identify an infiltrate suggestive of acute chest syndrome in patients with SCD compared to chest radiography as the gold standard., Methods: This was a prospective observational study in 2 urban pediatric emergency departments to evaluate the accuracy of point-of-care lung ultrasonography in identifying patients with SCD who were aged 0 to 21 years and had an infiltrate suggestive of acute chest syndrome compared with chest radiography. Clinicians and trainees with point-of-care lung ultrasonographic training obtained informed consent and performed investigational point-of-care lung ultrasonography to evaluate for lung consolidation. A blinded point-of-care lung ultrasonographic expert reviewed results for quality assurance and agreement. Accuracy, sensitivity, specificity, likelihood ratios, and positive and negative predictive value were calculated for point-of-care lung ultrasonography test performance characteristics, with chest radiography as a reference standard., Results: Point-of-care lung ultrasonography was performed on 191 SCD patients with a mean age of 8 years; 41% were female patients, and there was a 17% prevalence of acute chest syndrome. Accuracy of point-of-care lung ultrasonography to detected acute chest syndrome was 92%, sensitivity was 88%, and specificity was 93% compared with that for chest radiography., Conclusion: Point-of-care lung ultrasonography is a feasible alternative to chest radiography for screening for acute chest syndrome in young patients with SCD. Further studies are needed to determine how this test performs within clinical practice., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Acute chest syndrome (ACS) is a major complication of sickle cell anaemia (SCA) and a leading cause for hospital admissions and death. We aimed to study the spectrum of clinical and laboratory features of ACS and to assess the predisposing factors and predictors of severity. A retrospective case-control cohort was studied by retrieving patient information from electronic medical records after ethical approval. One hundred adolescents and adults with SCA and hospital admissions for ACS were identified through the discharge summaries, along with 20 additional patients presenting with VOC, but without ACS (controls). Among the patients with ACS, fever (>38.5 °C), reduced oxygen saturation (<95) and asplenia significantly differed when compared to those of controls (p < 0.05, chi-squared test). The degree of severity was reflected in the use of non-invasive ventilation (NIV), simple and exchange transfusions, and the presence of bilateral pleural effusions and multi-lobar atelectasis/consolidation, which were significantly higher in the cases with ACS than in the controls. Lower haemoglobin (Hb) and high WBC counts were also significantly different between the two groups (p < 0.05, Student's t test). Using logistic regression, our study further demonstrated that asplenia, fever, and reduced O 2 saturation, along with low Hb and leukocytosis, were important predictors for the development of ACS.

Background: Individuals with sickle cell disease (SCD) are at high risk of developing life-threatening complications, particularly acute chest syndrome (ACS) postoperatively. The perioperative factors associated with the development of ACS in children with SCD after splenectomy have not been clearly identified., Materials and Methods: We retrospectively reviewed medical records of all children who underwent splenectomy at our institution between 1997 and 2017 with the goal of identifying perioperative factors associated with postoperative ACS. Categorical and noncategorical variables were compared using Fisher's exact test and Student's two-tailed t-test, respectively., Results: Sixty-five patients with SCD underwent splenectomy at a median of 4.0 (interquartile range [IQR] 2.0-8.0) years of age. A laparoscopic approach was used for 64 (98.5%) patients. Fifty-six (86.2%) underwent laparoscopic total splenectomy, and eight (12.3%) underwent laparoscopic partial splenectomy, of which two were converted to open. One had an open partial splenectomy (1.5%). Of the 65 patients, 10 (15.4%) developed ACS with a mean time to diagnosis of 49.0 ± 34.5 h. Children who developed ACS had a higher postoperative median pain score of 6.8 (IQR 5.1-9.1) versus 2.7 (IQR 1.6-4.2), P < 0.001, higher median pain score area under the curve 111.5 (IQR 76.9-169.1) versus 47.3 (IQR 30.5-78.3), P = 0.01, and received more total morphine equivalents (median 1.4 [IQR 0.4-2.7] versus 0.5 [IQR 0.3-0.9] mg/kg, respectively; P = 0.003), compared with children who did not develop ACS., Conclusions: Significant postoperative pain may be an early sign of ACS that could be worsened by opioid use, supporting the investigation of nonopioid pain control options in this patient population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Sickle cell disease (SCD) is a group of inherited blood disorders affecting the hemoglobin, shortening the lifespan of erythrocytes, and causing them to take on a distinctive sickled shape that can lead to vaso-occlusion. Current treatment aims to reduce morbidity and mortality through hydroxyurea, erythrocyte transfusion, and hematopoietic stem cell transplantation. This article reviews the disease process, typical presentations, complications, and acute and chronic treatment options.

Introduction: The rate of bacterial infections in children with sickle cell disease (SCD) has decreased in recent years, mainly due to penicillin prophylaxis and vaccination., Objectives: To determine the rate of severe bacterial infection (SBI) in a cohort of children with SCD and to describe low-risk factors for confirmed SBI (CSBI) and acute chest syndrome (ACS)., Methods: This 11-year retrospective cohort study included children with febrile SCD admitted to a reference hospital in Spain. A case-control study was performed comparing patients diagnosed with SBI to those without SBI, and subanalyses for groups with CSBI and ACS were carried out., Results: A total of 316 febrile episodes were analyzed; 69 (21.8%) had confirmed or possible SBI. Thirteen of those had CSBI (4.1%), eight urinary tract infection, and five bacteremia/sepsis. Among the cases of possible SBI, the majority had ACS (54/56; 96.4%). Age >3 years, absence of central venous catheter, hemodynamic stability, and procalcitonin <0.6 ng/ml were low-risk factors for CSBI, whereas normal oxygen saturation and C-reactive protein <3 mg/dl were low-risk factors for ACS, with negative predictive values (NPV) of 98.3%, 97.4%, 96%, 97.2%, 87.5%, and 85.8%, respectively., Conclusion: In this cohort of children with SCD who were well vaccinated and received adequate prophylaxis, we found a low rate of bacteremia and CSBI. We described several low-risk factors for CSBI and ACS, all of them with a high NPV. These findings may help to develop a risk score to safely select the patients that could be managed with a more conservative approach., (© 2019 Wiley Periodicals, Inc.)

Background: Sickle cell anaemia (SCA) is a chronic inflammatory disorder with multiple organ manifestations including acute and long-term pulmonary dysfunction., Aims/objectives: To assess lung function of children with SCA and determine the possible role of acute chest syndrome (ACS), serum inflammatory cytokines, highly sensitive C-reactive protein (hs-CRP), leucocytes and 25-hydroxyvitamin D on the development of impaired lung function., Subjects and Methods: Lung function of 76 children with SCA was determined by spirometer and classified into normal or impaired. Sociodemographic, clinical, haematological, biochemical and immunological data of the two groups were compared by univariate and multivariate analyses., Results: Fifty (65.8%) patients had impaired lung function, comprising of 30.3%, 3.9% and 31.6% with restrictive, obstructive and mixed disease patterns, respectively. Children with previous ACS were 3.6 times more likely to have impaired lung function than those without ACS (82.1% vs 56.3%, p = 0.02, OR 3.6, 95% CI 1.2-10.8). Interleukin (IL)-8 and hs-CRP were significantly higher in patients with impaired lung function (p = 0.02 and <0.001, respectively). Using logistic regression, previous ACS (OR 5.8, 95% CI 1.1-5.8, p = 0.03) and higher serum IL-8 levels (OR 3.0, 95% CI 1.0-8.0, p = 0.02) independently predicted the presence of abnormal lung function., Conclusions: Lung dysfunction, predominantly restrictive pattern, is common in SCA and is associated with previous ACS and alterations in immunological markers, especially serum IL-8 and hs-CRP., Abbreviations: ACS: acute chest syndrome; CBT: chronic blood transfusion; ELISA: enzyme-linked immunosorbent assay; FEV 1 : forced expiratory volume in 1 s; FVC: forced vital capacity; HPLC: high-density liquid chromatography; hs-CRP: highly sensitive C-reactive proteins; HU: hydroxyurea; IL: Interleukin; PEFR: peak expiratory flow rate; SEM: standard error of the mean; TLC: total lung capacity; 25-OHD: 25-hydroxyvitamin D; VOC: vaso-occlusive crisis; WGH: Wesley Guild Hospital.

Acute chest syndrome (ACS) is a leading cause of mortality in patients with sickle cell disease (SCD). Systemic corticosteroids decrease ACS severity, but the risk of readmission for vaso-occlusive crises (VOC) has limited their use. The efficacy of inhaled corticosteroids (ICS) as a safer alternative is currently unknown. An observational, historic cohort study compared patients with SCD with ACS who received ICS at admission (ICS) to those who did not (non-ICS). Outcome measures included rates of transfusion, oxygen requirement, BiPAP initiation, PICU transfer, intubation, readmission, hospital cost, and length of stay. One hundred twenty patients with SCD (55 non-ICS, 65 ICS) were included. A significantly higher proportion of the non-ICS group had bilateral infiltrates, but fewer had asthma. More children in the ICS group had BiPAP initiated, however transfer to the PICU, intubation, transfusion rates, oxygen requirement, hospital cost, length of stay, and readmission rates did not differ between groups. Regression analysis did not reveal any differences in outcomes, nor were outcomes changed when patients were separated based on the presence or absence of asthma. In this observational cohort study, ICS did not demonstrate a significant reduction in ACS morbidity, though ICS use should be studied in a prospective manner., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF)., Case Report: An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission., Conclusions: Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy., (© 2018 AABB.)

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA., (© 2018 John Wiley & Sons Ltd.)

Acute chest syndrome (ACS) is a common and serious lung complication in sickle cell disease. A retrospective medical chart review was performed over a 6-year period in all pediatric ACS patients to investigate whether factors during the initial hospitalization were associated with recurrent ACS episodes. There were 386 episodes of ACS: 149 had only 1 episode of ACS, and 76 had >1 episode of ACS; 172 (76.4%) had hemoglobin SS, and 39 (17.3%) had hemoglobin SC. The most common presenting features were fever (83%), pain (70%), and cough (61%), which changed with the number of ACS episodes. Children <4 years old were at greatest risk of recurrent ACS (P=0.018). In addition, history of asthma (adjusted incident rate ratio [IRR]=1.52; 95% confidence interval [CI], 1.22-1.98; P<0.0001), shortness of breath (IRR, 1.29; 95% CI, 1.02-1.62; P=0.033), and length of hospital stay (IRR, 1.04; 95% CI, 1.01-1.08; P=0.017) were significantly associated with prospective ACS events. Multiple episodes of ACS are common in sickle cell disease, and certain risk factors during the initial hospitalization are associated with recurrent ACS.

Competing Interests: Competing interests: Yves Pastore has received personal fees from Pfizer, Novartis and ApoPharma, outside the submitted work. Veronique Naessens has received personal fees in the form of renumeration for participation on the advisory boards of Pfizer and Alexion, and lecture fees from ApoPharma. The Canadian Haemoglobinopathy Association received unrestricted educational funds from ApoPharma, Novartis and Pfizer to support production of the consensus statement. No other competing interests were declared.

The American Society for Apheresis (ASFA) conducted a one-day consensus conference on red blood cell exchange (RBCx) in sickle cell disease (SCD) during its annual meeting in San Antonio, TX, on May 5, 2015. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to pathophysiology of SCD and use of RBCx in the management of various complications. These questions were provided to the seven invited speakers who are the experts in the field of SCD. Two experts in the field moderated the proceedings of the conference, which was attended by more than 150 participants. After each presentation, there was a summary of the main points by the moderators and an open discussion with questions from the audience. A video recording of the proceedings, as well as each presentation, was made available to the authors. Each author's summary was reviewed and approved by the respective speaker before submission of this manuscript. The subcommittee also developed several key questions to generate a consensus amongst the speakers on key issues for using RBCx for patients with SCD., (© 2016 Wiley Periodicals, Inc.)

Pulmonary embolism is a life-threatening and potentially lethal disease. Its incidence in children with sickle cell disease is probably underestimated and pediatric case reports in the literature are rare. Moreover, symptoms can mimic an acute chest syndrome. We report on the case of a 17-year-old boy with SS sickle cell disease, admitted for chest pain with dyspnea and tachycardia. Pulmonary angiography revealed a partial bilateral obstructive pulmonary embolism. We did not find any deep venous thrombosis or thrombophilia. The progression was rapidly favorable with anticoagulant therapy. We recommend a pulmonary angiography for any chest pain that does not evolve favorably in a child with sickle cell disease. Large series of pediatric patients would be useful to establish diagnostic and therapeutic guidelines., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper-reactivity) is an intrinsic component of Sickle Cell Disease (SCD) and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 nonasthmatic individuals with SCD. Participants received once daily mometasone furoate 220 mcg dry powder inhalation or placebo for 16 weeks. The primary outcome was feasibility (the number who complete the trial divided by the total number enrolled) with prespecified efficacy outcomes including daily pain score over time (patient reported) and change in soluble vascular cell adhesion molecule (sVCAM) levels between entry and 8-weeks. For the primary outcome of feasibility, the result was 96% (52 of 54, 95% CI 87%-99%) for the intent-to-treat analysis and 83% (45 of 54, 95% CI 71%-91%) for the per-protocol analysis. The adjusted treatment effect of mometasone was a reduction in daily pain score of 1.42 points (95%CI 0.61-2.21, P = 0.001). Mometasone was associated with a reduction in sVCAM levels of 526.94 ng/mL more than placebo (95% CI 50.66-1003.23, P = 0.03). These results support further study of ICS in SCD including multicenter trials and longer durations of treatment. www.clinicaltrials.gov (NCT02061202)., (© 2017 Wiley Periodicals, Inc.)

Purpose of Review: The current review outlines the challenges in managing pregnant women with sickle-cell anemia, who are at risk of becoming critically ill during pregnancy., Recent Findings: Sickle obstetric patients pose unique challenges to the anesthetist and intensivist. We discuss the role of prophylactic transfusions for specific indications like acute anemia and twin pregnancies. The management and prevention of vaso-occlusive crises and chest crisis are also outlined. The role of the multidisciplinary team cannot be overstated.Massive obstetric hemorrhage in this population is difficult, and unique considerations such as cell-saver technology and tranexamic acid usage are discussed. Secondary complications such as pulmonary hypertension and stroke are also considered, with a summary of the latest treatment guidelines., Summary: This is a challenging cohort of pregnant patients who have a significantly increased morbidity and mortality. This review aims to aid management of these patients on the labor ward for both obstetric anesthetists and intensivists.

Acute and chronic pulmonary complications are frequent in sickle cell disease (SCD), with different spectrum and characteristics in children and adults. Chronic hypoxia is frequent and plays a role in several respiratory complications in SCD. Furthermore, hypoxia has been associated with a higher risk of cerebral ischemia. Despite differing oxygen affinity between hemoglobin A and S, standard pulse oximetry was shown to be accurate in diagnosing hypoxia in SCD patients. Whereas acute hypoxia management is similar to non-SCD patients, chronic hypoxia treatment is mainly based on a transfusion program rather than long-term oxygen therapy. Acute chest syndrome (ACS) is the foremost reason for admission to the intensive care unit and the leading cause of premature death. Guidelines on its management have recently been published. Asthma appears to be a different comorbidity and may increase the risk of vaso-occlusive crisis, ACS, and early death. Its management is not specific in SCD, but systemic steroids must be used carefully. Pulmonary hypertension (PH) is a major risk factor of death in adult patients. In children, no association between PH and death has been shown. Elevated tricuspid regurgitant velocity was associated with lower performance on the 6-min walk test (6MWT) but its long-term consequences are still unknown. These differences could be due to different pathophysiology mechanisms. Systematic screening is recommended in children. Regarding lung functions, although obstructive syndrome appears to be rare, restrictive pattern prevalence increases with age in SCD patients. Adaptation to physical exercise is altered in SCD children: they have a lower walking distance at the 6MWT than controls and can experience desaturation during effort, but muscular blood flow regulation maintains normal muscular strength. Sleeping disorders are frequent in SCD children, notably Obstructive sleep apnea syndrome (OSAS). Because of the neurological burden of nocturnal hypoxia, OSAS care is primordial and mainly based on adenotonsillectomy, which has been shown to reduce ischemic events. The high morbidity and mortality related to pulmonary impairments in SCD require a careful pulmonary assessment and follow-up. Mainly based on clinical examination, follow-up aims to the diagnosis of SCD-related respiratory complications early in these children., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Sickle cell disease (SCD) affects approximately 100,000 individuals in the United States. Due to alterations in the structural conformation of hemoglobin molecules under deoxygenated conditions, patients with SCD are predisposed to numerous sequelae, many of which require acute intervention., Objective: Our aim was to provide emergency physicians with an evidence-based update regarding the diagnosis and management of SCD complications., Discussion: SCD patients experience significant morbidity and mortality secondary to cerebrovascular accident, acute chest syndrome, acute vaso-occlusive pain crises, SCD-related multi-organ failure, cholecystitis, acute intrahepatic cholestasis, acute sickle hepatic crisis, acute hepatic sequestration, priapism, and renal disease. Emergency physicians must recognize acute manifestations of SCD in order to deliver timely management and determine patient disposition., Conclusions: A comprehensive review of the emergency department management of acute SCD complications is provided. Comprehensive understanding of these aspects of SCD can assist physicians in expediting patient evaluation and treatment, thus decreasing the morbidity and mortality associated with this hemoglobinopathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' Emergency-Room admissions and hospitalizations. Acute chest syndrome (ACS), a life-threatening complication, can occur during VOC, be fatal and prolong hospitalization. No predictive factor identifies VOC patients who will develop secondary ACS., Methods: This prospective, monocenter, observational study on SS/S-β0thalassemia SCD adults aimed to identify parameters predicting ACS at Emergency-Department arrival. The primary endpoint was ACS onset within 15days of admission. Secondary endpoints were hospitalization duration, morphine consumption, pain evaluation, blood transfusion(s) (BT(s)), requiring intensive care and mortality., Findings: Among 250 VOCs included, 247 were analyzed. Forty-four (17.8%) ACSs occurred within 15 (median [IQR] 3 [2, 3]) days post-admission based on auscultation abnormalities; missing chest radiographs excluded three patients. Comparing ACS to VOC, respectively, median hospital stay was longer 9 [7-11] vs 4 [3-7] days (p<0.0001), 7/41 (17%) vs 1/203 (0.5%) required intensive care (p<0.0001), and 20/41 (48.7%) vs 6/203 (3%) required BTs (p<0.0001). No patient died. The multivariate model retained reticulocyte and leukocyte counts, and spine and/or pelvis pain as being independently associated with ACS; the resulting ACS-predictive score's area under the ROC was 0.840 [95% CI 0.780-0.900], 98.8% negative-predictive value and 39.5% positive-predictive value for the real ACS incidence., Interpretation: The ACS-predictive score is simple, easily applied and could change VOC management and therapeutic perspectives. Assessed ACS risk could lead to earlier discharges or close monitoring and rapid medical intensification to prevent ACS., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In contemporary practice with early catheterization in most patients with suspected acute myocardial infarction, the clinical utility of new or presumably new left bundle branch block (LBBB) as a diagnostic criterion equivalent to ST-segment elevation is not well established. This study therefore aimed to determine the predictive value of LBBB for the diagnosis of acute transmural myocardial infarction (or ST-segment elevation myocardial infarction, STEMI)., Patients and Methods: Between November 2006 and December 2011, 1,139 consecutive patients presenting to the heart center of the University of Cologne with suspected STEMI were examined. Of these patients, 935 presented with ST elevation, 72 with LBBB, and 132 had neither of these ECG changes. The diagnosis was confirmed with immediate coronary angiography., Results: Compared with ST-segment elevation, LBBB was associated with a higher prevalence of cardiovascular risk factors and end-organ damage, and more patients with LBBB presented with pulmonary edema or cardiogenic shock (Killip III/IV). STEMI was confirmed in 58.3 % of patients with LBBB and in 86.4 % with ST-segment elevation. The sensitivity (0.38 [0.29-0.46]; odds ratio: 1.24) and specificity (0.67 [0.58-0.77]) of LBBB for the prediction of STEMI were low. However, the additional assessment of troponin T (> 0.1 µg/l) increased the predictive value of LBBB significantly. After adjusting for age and gender, no difference in mortality was found between the groups., Conclusion: LBBB with acute chest pain characterizes a cohort of patients with high morbidity and mortality. For the triage of these patients at first contact, additional criteria should be evaluated, which could increase the specificity of LBBB for the diagnosis of STEMI.

Sickle cell anemia results from a single amino acid substitution in the gene encoding the β-globin subunit. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. Hashimoto's thyroiditis is a common thyroid disease now recognized as an auto-immune thyroid disorder, it is usually thought to be haemolytic autoimmune anemia. We report the case of a 32 years old women admitted for chest pain and haemolysis anemia in which Hashimoto's thyroiditis and sickle cell anemia were found. In our observation the patient is a young woman whose examination did not show signs of goitre but the analysis of thyroid function tests performed before an auto-immune hemolytic anemia (confirmed by a high level of unconjugated bilirubin and a Coombs test positive for IgG) has found thyroid stimulating hormone (TSH) and positive thyroid antibody at rates in excess of 4.5 times their normal value. In the same period, as the hemolytic anemia, and before the atypical chest pain and anguish they generated in the patient, the search for hemoglobinopathies was made despite the absence of a family history of haematological disease or painful attacks in childhood. Patient electrophoresis's led to research similar cases in the family. The mother was the first to be analyzed with ultimately diagnosed with sickle cell trait have previously been ignored. This case would be a form with few symptoms because the patient does not describe painful crises in childhood or adolescence.