[Sickle cell disease - common and dangerous complications]. / ABC om Sicklecellsjukdom ­ vanliga och farliga komplikationer.

Sickle cell disease is a genetic disorder affecting hundreds of thousands of people worldwide. This article will focus on the most common and dangerous acute complications to sickle cell disease. Vaso-occlusive crisis is the most common manifestation of sickle cell disease. Rapid pain relief and treating the underlying cause are cornerstones of the treatment. Acute chest syndrome is the most common cause for intensive care unit admission and death among adult patients with sickle cell disease. The condition is treated as vaso-occlusive crises, but patients often need blood transfusions and respiratory support. Patients with sickle cell disease have an increased risk of stroke. Treatment follows the usual guidelines for stroke with the addition of blood- or exchange transfusions. Splenic sequestration is a rare but acute and life-threatening complication, most commonly seen in children. The condition can quickly lead to hypovolemic shock and the treatment aims to maintain adequate circulation and to treat the underlying cause.

[Clinical, aetiological and therapeutic features of severe sickle cell related vaso-occlusive crisis at the Sylvanus Olympio University Hospital, Lomé]. / Crise vaso-occlusive drépanocytaire sévère: aspects cliniques, étiologiques et thérapeutiques au CHU Sylvanus Olympio de Lomé.

Introduction: vaso-occlusive crisis (VOC) is the most common manifestation of sickle cell disease and the leading cause of hospitalization among affected children. The purpose of this study is to describe the clinical features of severe VOCs, to determine the etiologies of infectious syndromes that accompany them and to describe their management. Methods: we conducted a descriptive cross-sectional study of 137 adult patients with sickle cell disease hospitalised for severe VOC in the Paediatric Department of the Sylvanus Olympio University Hospital from 1st January 2009 to 31st December 2011. Results: the majority of patients (n=98; 71.5%) had homozygous sickle cell (SS), followed by double heterozygous SC disease (n=28; 20.5). The median of consultation time was 4.7 ± 4.4 days. Treatment before admission was based on antibiotics (28.5%). VOCs were mainly osteoarticular (70.8%). In 98.5% of cases, an associated bacterial infection was confirmed (48.9%) or suspected (49.6%). The main etiologies included acute chest syndrome (26.3%), acute osteomyelitis (10.9%), urinary tract infection (6.6%) and septicaemia (3.6%). One germ was isolated from 14.6% of patients: Escherichia coli (30%), followed by Klebsiella pneumoniae (25%), Staphylococcus aureus (15%), Salmonella typhi (10%), Streptococcus pneumoniae (5%), Streptococcus D (5%), Enterobacter (5%) and Acinetobacter (5%). Mortality rate was 2.2%. The average length of stay in hospital was 11.4 ± 8.8 days. Conclusion: severe sickle cell-related vaso-occlusive crisis is mainly associated with bacterial infections in tropical environments. Appropriate and early antibiotic therapy is the essential therapeutic means to prevent or treat these patients.

Acute chest syndrome in sickle cell disease.

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.

SNAP: Supportive non-invasive ventilation for acute chest syndrome prevention for hospitalized children with sickle cell disease: Perspectives of patients, parents, and the healthcare team.

RATIONALE: Acute chest syndrome (ACS) often develops during hospitalizations for sickle cell disease (SCD) vaso-occlusive episodes and may be triggered by a combination of chest wall splinting, opioid use, hypoventilation, and atelectasis. In 2017, Boston Medical Center's general pediatric inpatient unit instituted the novel use of bi-level positive airway pressure (BiPAP) as "supportive non-invasive ventilation for ACS prevention" (SNAP) to prevent ACS and respiratory decompensation. OBJECTIVE: The goals of this qualitative study were to identify perceived benefits, harms, facilitators, and barriers to use of SNAP. METHODS: We conducted semi-structured key informant interviews at three sites with different levels of SNAP implementation (Site 1: extensive implementation; Site 2: limited implementation; Site 3: not yet implemented) regarding experiences with and/or perceptions of SNAP. Interviews and coding were guided by the Promoting Action on Research Implementation in Health Services (PARiHS) framework. RESULTS: Thirty-four participants (physicians, nurses, respiratory therapists, child life specialists, psychologists, youth with SCD, and parents) completed interviews. Major themes included: (i) participants perceive BiPAP as effective at preventing ACS, and for those with medically stable ACS, for preventing respiratory decompensation. (ii) BiPAP use is appropriate on the general pediatric inpatient unit for medically stable patients with SCD. (iii) Improving the patient experience is the most important factor to optimize acceptance of BiPAP by patients and families. CONCLUSION/FUTURE DIRECTIONS: SNAP is perceived as effective and appropriate for hospitalized pediatric patients with SCD. Improving the patient experience is the biggest challenge. These data will inform a future protocol for a multicenter hybrid effectiveness/implementation trial of SNAP.

Burden and outcome of respiratory morbidities among children and adolescents with sickle cell disease-A retrospective review of emergency presentations in some Nigerian tertiary institutions.

BACKGROUND: Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to describe the spectrum and outcome of respiratory illnesses among SCD childrenand adolescentadmissions in ten Nigerian tertiary hospitals. METHOD: A retrospective review of the SCD admission records of children and adolescents with a confirmed diagnosis of respiratory illnesses from 2012 to 2021 in ten tertiary health facilities across five geopolitical zones in Nigeria was conducted. The data, collectedbetween March and June 2023, included the age, sex, diagnosis, complications, duration and outcome of hospitalization. RESULTS: Of the 72,333 paediatric admissions, 7,256 (10.0%) had SCD; the proportion of SCD from the total admission ranged from 2.1 to 16.3% in the facilities. Of the 7,256 children and adolescents with SCD, 1,213 (16.7%) had respiratory morbidities. Lower respiratory disease was the most common (70.0%) respiratory entity and the majority were pneumonia (40.1.0%), followed by acute chest syndrome (26.7%). Seventeen (1.4%) patients died; all had lower respiratory diseases [(acute chest syndrome ACS (11, 64.7%), pneumonia; 5, 29.4%, and asthma (1, 5.9%). Based on the proportion of deaths among overall SCD, the 17 death cases contributed 9.4% (95% CI 5.9 to 14.5). Factors associated with deaths included duration of hospitalization less than 72 hours and lower respiratory tract diseases. CONCLUSION: Sickle cell disease is a major contributor to hospitalization among Nigerian children and adolescents, with high respiratory morbidity and mortality. Pneumonia and acute chest syndrome were associated with mortality, andthe highest risk of death within the first 72 hours.

Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease.

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05-1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67-0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49-0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065-1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.

Sputum interleukin-6 level as a marker of severity during acute chest syndrome in children with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of morbimortality in sickle cell disease (SCD). In this prospective observational study, we investigated sputum interleukin-6 (IL-6) level as an ACS severity marker during 30 ACS episodes in 26 SCD children. Sputum IL-6 levels measured within the first 72 h of hospitalisation for ACS were significantly higher in patients with oxygen requirement ≥2 L/min, ventilation (invasive and/or non-invasive) length ≥5 days, bilateral and/or extensive opacities on chest X-ray or erythrocytapheresis requirement. Sputum IL-6 could serve as an ACS severity marker to help identify patients requiring targeted anti-inflammatory treatments such as tocilizumab.

New Horizons in Emergency Department Management of Pediatric Sickle Cell Disease.

ABSTRACT: Sickle cell disease (SCD) is an important topic for emergency medicine audiences because complications of the disease account for a large proportion of hematologic emergencies that are seen in the emergency department each year. Early recognition and aggressive management of emergency complications of SCD can help to reduce the morbidity and mortality associated with this disease. Although the treatment recommendations for some complications of SCD are based on expert opinion, there has been advancement in the understanding of the pathogenesis of the disease and evidence regarding the treatment options available for managing acute complications. This continuing medical education article will provide a summary of the clinical manifestation and management of the most common acute complications of SCD: infection, vaso-occlusive episode, acute chest syndrome, splenic sequestration, stroke, and priapism.

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death.

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

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.

Plasma sphingolipids in patients with sickle cell disease: Multiple-site vaso-occlusive crises could be associated with lower sphingolipid levels.

Although sickle cell disease (SCD) and its manifestations have been associated with various lipid alterations, there are a few studies exploring the impact of sphingolipids in SCD. In this study, we determined plasma ceramide (Cer) and sphingomyelin (CerPCho) species and investigated their association with the crisis in SCD. SCD patients (N = 27) suffering from vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) were involved in this study. Blood samples were drawn at crisis and later at steady state periods. Clinical history, white blood cell count (WBC), C-reactive protein and lactate dehydrogenase (LDH) levels were recorded. 16:0, 18:0, 20:0, 22:0 Cer and 16:0, 18:0, 24:0 CerPCho were measured via LC-MS/MS. All measured Cer and CerPCho levels of SCD patients at crisis and steady-state were found to be similar. Inflammation-related parameters were significantly higher in patients with ACS compared to single-site VOC. Patients with multiple-site VOC were found to have significantly lower sphingolipid levels compared with those with single-site VOC, at crisis (16, 18, 24 CerPCho and 18, 22 Cer) and at steady-state (24:0 CerPCho and 18 Cer). Our results show that sphingolipid levels in SCD patients are similar during crisis and at steady state. However, lower sphingolipid levels appear to be associated with the development of multiple-site VOC. Since the differences were observed at both crisis and steady-state, sphingolipid level could be an underlying factor associated with crisis characteristics in patients with SCD.

Factors Associated with Overt Stroke in Children and Adolescents with Sickle Cell Disease: A Retrospective Cohort Study.

Sickle cell disease (SCD) is associated with a high occurrence of complications due to vaso-occlusive phenomenon such as stroke. This retrospective cohort study aimed to examine the clinical and laboratory characteristics of 120 children and adolescents with SCD and analyze the factors associated with overt stroke incidence. All relevant data were obtained from patient medical records. Survival analysis was used to compare the demographic, clinical, and laboratory characteristics between patients with and those without overt stroke. The patients were 52.5% female with a mean (SD) age of 11.2 (4.3) years. The incidence of overt stroke in this cohort was nine out of 956.7 patient-years, resulting in an incidence density of 0.94 cases/100 patient-years. Reports of greater than or equal to two previous attacks of dactylitis and greater than or equal to three episodes of acute chest syndrome (ACS)/pneumonia were associated with overt stroke and an increase in reticulocyte count and red blood cell distribution width (RDW). In conclusion, a history of a high number of dactylitis, ACS/pneumonia, increased RDW, and reticulocytosis was associated with overt stroke occurrence in children and adolescents with SCD. Future studies with a higher stroke incidence in the evaluated sample are necessary to confirm this hypothesis.

Enhancing diagnostic precision for acute chest syndrome in sickle cell disease: insights from dual-energy CT lung perfusion mapping.

PURPOSE: Acute chest syndrome (ACS) is secondary to occlusion of the pulmonary vasculature and a potentially life-threatening complication of sickle cell disease (SCD). Dual-energy CT (DECT) iodine perfusion map reconstructions can provide a method to visualize and quantify the extent of pulmonary microthrombi. METHODS: A total of 102 patients with sickle cell disease who underwent DECT CTPA with perfusion were retrospectively identified. The presence or absence of airspace opacities, segmental perfusion defects, and acute or chronic pulmonary emboli was noted. The number of segmental perfusion defects between patients with and without acute chest syndrome was compared. Sub-analyses were performed to investigate robustness. RESULTS: Of the 102 patients, 68 were clinically determined to not have ACS and 34 were determined to have ACS by clinical criteria. Of the patients with ACS, 82.4% were found to have perfusion defects with a median of 2 perfusion defects per patient. The presence of any or new perfusion defects was significantly associated with the diagnosis of ACS (P = 0.005 and < 0.001, respectively). Excluding patients with pulmonary embolism, 79% of patients with ACS had old or new perfusion defects, and the specificity for new perfusion defects was 87%, higher than consolidation/ground glass opacities (80%). CONCLUSION: DECT iodine map has the capability to depict microthrombi as perfusion defects. The presence of segmental perfusion defects on dual-energy CT maps was found to be associated with ACS with potential for improved specificity and reclassification.

Managing sickle cell disease and related complications in pregnancy: results of an international Delphi panel.

ABSTRACT: Data to guide evidence-based management of pregnant people with sickle cell disease (SCD) are limited. This international Delphi panel aimed to identify consensus among multidisciplinary experts for SCD management during pregnancy. The 2-round Delphi process used questionnaires exploring 7 topics (antenatal care, hydroxyurea use, transfusion, prevention of complications, treatment of complications, delivery and follow-up, and bottlenecks and knowledge gaps) developed by a steering committee. Thirteen panelists (hematologists, physiologists, obstetricians, maternal fetal medicine, and transfusion medicine physicians) from the United States, the United Kingdom, Turkey, and France completed the first survey; 12 panelists completed the second round. Anonymized responses were collected and summarized by a contract research organization (Akkodis Belgium). Consensus and strong consensus were predefined as 75% to 90% (9-10 of 12) and >90% (≥11 of 12) of panelists, respectively, agreeing or disagreeing on a response to a predefined clinical scenario or statement. In several areas of SCD management, consensus was achieved: experts recommended performing at least monthly multidisciplinary antenatal follow-up, administering prophylactic aspirin for preeclampsia prevention between gestational weeks 12 and 36, initiating prophylactic transfusion therapy in certain cases, or choosing automated red blood cell exchange over other transfusion methods for patients with iron overload or severe acute chest syndrome. No consensus was reached on several topics including the prophylactic aspirin dose, indications for starting infection prophylaxis, routine use of prophylactic transfusions, or use of prophylactic transfusions for preventing fetal complications. These recommendations could inform clinical care for patients with SCD who are pregnant in the absence of large clinical trials involving this population; the identified knowledge gaps can orient future research.

Oxygen saturation thresholds in managing sickle cell disease at US children's hospitals.

BACKGROUND: Adequate oxygen saturation (SpO2 ) is crucial for managing sickle cell disease (SCD). Children with SCD are at increased risk for occult hypoxemia; therefore, understanding SpO2 threshold practices would help identify barriers to oxygen optimization in a population sensitive to oxyhemoglobin imbalances. We investigated SpO2 cutoff levels used in clinical algorithms for management of acute SCD events at children's hospitals across the United States, and determined their consistency with recommended national guidelines (SpO2  > 95%). METHODS: Clinical pathways and algorithms used for the management of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) in SCD were obtained and reviewed from large children's hospitals in the United States. RESULTS: Responses were obtained from 94% (140/149) of eligible children's hospitals. Of these, 63 (45%) had available clinical algorithms to manage VOC and ACS. SpO2 cutoff was provided in 71.4% (45/63) of clinical algorithms. Substantial variation in SpO2 cutoff levels was noted, ranging from ≥90% to more than 95%. Only seven hospitals (5% of total hospitals and 15.6% of hospitals with clinical algorithms available) specified oxygen cutoffs that were consistent with national guidelines. Hospitals geographically located in the South (46.8%; n = 29/62) and Midwest (54.8%; n = 17/31) were more likely to have VOC and ACS clinical algorithms, compared to the Northeast (26.5%; n = 9/34) and West (36.4%; n = 8/22). CONCLUSION: There is inconsistency in the use of clinical algorithms and oxygen thresholds for VOC and ACS across US children's hospitals. Children with SCD could be at risk for insufficient oxygen therapy during adverse acute events.

Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sß°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

How I treat sickle cell disease in pregnancy.

ABSTRACT: Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.