Prevalence of Respiratory Symptoms in Children with Sickle Cell Disease Compared to Children with Other Hematological Diseases.

Abstract Acute chest syndrome (ACS) and pulmonary hypertension are complications of sickle cell disease (SCD). The effects of pre-existing respiratory symptoms on the frequency of complications of SCD, such as vaso-occlusive crises and ACS, have not been fully explored. Many therapeutic options exist for patients with reactive airway disease or other recurrent respiratory problems. Control of associated symptoms may help prevent the occurrence of ACS and other sickle cell-related problems. We compared the prevalence of respiratory symptoms in SCD patients compared to patients with other hematological disorders. Methods: Two questionnaires (one for patients with SCD, one for patients with other hematological disorders) were developed, which included questions regarding respiratory symptoms (especially wheezing and cough, frequency of these symptoms, previous diagnosis of asthma), personal history and environmental exposure. The study was approved by the Institutional Review Board, and patients and their caregivers were interviewed during a routine visit to the outpatient hematology clinic after giving informed consent. Results: To date, 124 subjects have been interviewed (62 males and 58 females, ages 3–18 years, mean age 10.1yrs), and 120 questionnaires were evaluable, including 59 from patients with SCD and 61 from the comparison group. Respiratory symptoms (wheezing and cough) were more frequent in SCD patients compared to patients with other hematological diseases. Wheezing was present in 34 (58%) SCD patients and in 20 (33%) patients in the other group (p<0.01). Twelve patients (20%) in the SCD group missed school due to respiratory problems (over half of them missed more than 7 days of school) compared to 4 (6%) patients (only 1 missing school for more than 7 days) in the other group (p<0.04). Hospitalization due to respiratory problems before the age of 2 years was more common in SCD patients: 23 (39%) compared to 8 (13%) in other hematological patients (p<0.003). Conclusions: The prevalence of pulmonary symptoms is higher in patients with SCD compared to patients with other hematological disorders and associated with frequent hospitalizations and school absences.

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Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome

International Journal of Molecular Sciences ◽

10.3390/ijms21238884 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8884

Author(s):

Joanna Gemel ◽

Yifan Mao ◽

Gabrielle Lapping-Carr ◽

Eric C. Beyer

Keyword(s):

Endothelial Cells ◽

Sickle Cell Disease ◽

Gap Junctions ◽

Extracellular Vesicles ◽

Sickle Cell ◽

Intercellular Junctions ◽

The Other ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Intercellular Connections

Intercellular junctions maintain the integrity of the endothelium. We previously found that the adherens and tight junctions between endothelial cells are disrupted by plasma extracellular vesicles from patients with sickle cell disease (especially those with Acute Chest Syndrome). In the current study, we evaluated the effects of these vesicles on endothelial gap junctions. The vesicles from sickle cell patients (isolated during episodes of Acute Chest Syndrome) disrupted gap junction structures earlier and more severely than the other classes of intercellular junctions (as detected by immunofluorescence). These vesicles were much more potent than those isolated at baseline from the same subject. The treatment of endothelial cells with these vesicles led to reduced levels of connexin43 mRNA and protein. These vesicles severely reduced intercellular communication (transfer of microinjected Neurobiotin). Our data suggest a hierarchy of progressive disruption of different intercellular connections between endothelial cells by circulating extracellular vesicles that may contribute to the pathophysiology of the endothelial disturbances in sickle cell disease.

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

American Journal of Hematology ◽

10.1002/ajh.24408 ◽

2016 ◽

Vol 91 (8) ◽

pp. E332-E333 ◽

Cited By ~ 3

Author(s):

Sarah G. Lazarus ◽

Michael Kelleman ◽

Olufolake Adisa ◽

April R. Zmitrovich ◽

Robert Hagbom ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Respiratory Symptoms ◽

Chest Radiographs ◽

Acute Chest Syndrome ◽

Cell Disease

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Presentation, Management and Outcomes of COVID-19 Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2020-138739 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 29-30

Author(s):

Nwabundo Anusim ◽

Ruby Gupta ◽

Hycienth O Ahaneku ◽

Candace Franklin ◽

Savitha Balaraman ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Respiratory Symptoms ◽

Bone Pain ◽

Globin Gene ◽

Morbidity And Mortality ◽

Polymerase Chain Reaction Test ◽

Acute Chest Syndrome ◽

Shortness Of Breath ◽

Cell Disease

Background Sickle cell disease (SCD) is an inherited disorder of red blood cell (RBC) caused by a mutation in the beta-globin gene resulting in abnormal hemoglobin known as hemoglobin S (HbS) or the sickle hemoglobin. Several clinical variants of SCD have been elucidated, all driven by two fundamental pathophysiologic processes: RBC hemolysis and intermittent vaso-occlusive vasculopathy resulting in tissue ischemia/infarction. These two processes underscore the many complications and eventual multi-organ damage that may develop in patients with the most severe types of SCD. Cardiopulmonary complications including heart failure, pulmonary hypertension and acute chest syndrome (ACS) are major drivers of morbidity and mortality among patients with SCD. With regards to ACS, patients often present with fever, cough and shortness of breath caused by vaso-occlusive crisis affecting the lungs. This is particular concerning in view of its similar features to symptomatic COVID-19 infection. Methods We retrospectively identified SCD patients with COVID-19 infection admitted to Beaumont hospitals in Michigan between March 1st 2020 and July 1st 2020. Data was abstracted using the ICD 10 code of U07. 1 for COVID-19, ICD 9 and 10 codes of 282.60 and D57 for sickle cell disease. We excluded patients with sickle cell trait. Data regarding the demographics, presentation, management and outcomes were abstracted. Results A total of eleven patients with sickle cell disease were identified as having a positive SARS-Cov19 polymerase chain reaction test (Table I). All were African American and predominantly female (64%) with a mean age of 44 (22-60) years and mean BMI of 30.2 kg/m2. Genotypes identified were HbSS in 5 (45%) patients, HbSC in 4 (36%), HbS/beta-thalassemia in 1 (9%) and HbS/alpha-thalassemia in 1 (9%). All of the patients had seen a haematologist since their diagnosis but none of the patients were on hydroxyurea, voxeloter, L-glutamine or crizanlizumab at admission. The predominant clinical presentation was fever, chest pain, chills, exertional shortness of breath and cough but this was not consistent across all patients. All the patients were managed with intravenous hydration, pain management as well as hydroxychloroquine/azithromycin per institutional guideline at that time. Three patients (cases 1-3) had recurrent visits to the hospital for similar symptoms and new bone pain crises. Case 1 had a pulmonary embolus which was evident on re-admission. Two patients (cases 3 and 10) succumbed to COVID-19. Two patients (cases 5 and 7) presented with bone pain crisis and no respiratory symptoms, but chest imaging was suggestive of COVID-19 infection necessitating treatment with antibiotics, possibly indicating that the virus can trigger vaso-occlusive crises without respiratory symptoms. Case 8 had a high Charlson comorbidity index and age over 60, had the lengthiest hospital stay complicated by renal failure and polyneuropathy, and was discharged to a long-term acute care facility: an outcome which is consistent with current data showing that the elderly and unfit patients are more likely to have a higher morbidity and mortality with COVID-19. Conclusion To date, there no compelling evidence to provide guidelines for the management of SCD patients with COVID-19. However, following existing recommendations in managing acute chest syndrome and those for COVID-19 symptomatic infection, is a good place to start. We continue to seek to improve management of these patients as new evidence of successful treatment emerges, and also encourage patients to participate in clinical trials. Disclosures No relevant conflicts of interest to declare.

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ECMO Therapy in Acute Chest Syndrome for Patients with Sickle Cell Disease: a Case Report and Literature Review

SN Comprehensive Clinical Medicine ◽

10.1007/s42399-021-00987-0 ◽

2021 ◽

Author(s):

Soi Avgeridou ◽

Ilija Djordjevic ◽

Anton Sabashnikov ◽

Kaveh Eghbalzadeh ◽

Laura Suhr ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Scientific Data ◽

Acute Chest Syndrome ◽

Data Sets ◽

Limited Data ◽

Cell Disease ◽

Life Saving ◽

Institutional Experience ◽

Ecmo Therapy

AbstractExtracorporeal membrane oxygenation (ECMO) plays an important role as a life-saving tool for patients with therapy-refractory cardio-respiratory failure. Especially, for rare and infrequent indications, scientific data is scarce. The conducted paper focuses primarily on our institutional experience with a 19-year-old patient suffering an acute chest syndrome, a pathognomonic pulmonary condition presented by patients with sickle cell disease. After implementation of awake ECMO therapy, the patient was successfully weaned off support and discharged home 22 days after initiation of the extracorporeal circulation. In addition to limited data and current literature, further and larger data sets are necessary to determine the outcome after ECMO therapy for this rare indication.

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Streptococcus pneumoniae and Its Virulence Factors H2O2 and Pneumolysin Are Potent Mediators of the Acute Chest Syndrome in Sickle Cell Disease

Toxins ◽

10.3390/toxins13020157 ◽

2021 ◽

Vol 13 (2) ◽

pp. 157

Author(s):

Joyce Gonzales ◽

Trinad Chakraborty ◽

Maritza Romero ◽

Mobarak Abu Mraheil ◽

Abdullah Kutlar ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Sickle Cell Disease ◽

Virulence Factors ◽

Sickle Cell ◽

Biological Activities ◽

Acute Chest Syndrome ◽

Antibiotics Resistance ◽

Cell Disease ◽

Antibiotic Drug ◽

Tract Infections

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 (H2O2) as a virulence strategy. Apart from H2O2, 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.

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To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

Transfusion Medicine and Hemotherapy ◽

10.1159/000512644 ◽

2021 ◽

pp. 1-5

Author(s):

Justin E. Juskewitch ◽

Craig D. Tauscher ◽

Sheila K. Moldenhauer ◽

Jennifer E. Schieber ◽

Eapen K. Jacob ◽

...

Keyword(s):

Pregnant Woman ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pregnancy Termination ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Childbearing Age ◽

Procedural Complications ◽

History Of ◽

Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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