Search Results (49)

Sickle cell disease (SCD) is one of the most common inherited blood disorders worldwide. Clinical manifestations are variable, but include hyposplenism, renal impairment, cardiovascular disease, respiratory complications, and cerebrovascular disease. Frequent painful vaso-occlusive crises, hospitalisations, and other physical and psychological ramifications can have profound effects, including children missing school time resulting in impaired academic performance and adults missing work leading to employment loss. This narrative review examines the possible risks and benefits of exercise in the SCD population. Regular exercise plays an important role in improving physical and mental health, but fears around the potential consequences of exercise for the SCD population are present in children, their families, schools, and other organisations. This can result in children not taking part in as much regular exercise as their peers and being excluded from group activities. Studies have suggested that healthcare professionals often do not discuss the possible benefits of physical exercise with patients, likely because there are no guidelines regarding a safe level of activity. An acute increase in inflammation secondary to exercise could increase the risk of vaso-occlusive crises, but regular physical activity is known to play an important role in disrupting chronic inflammation across a wide range of pro-inflammatory diseases. Indeed, studies have demonstrated positive responses to exercise in the SCD population, from improvements in skeletal muscle microvasculature to performance in cardiovascular tests. It is important that recommendations are developed regarding types of exercise and the ideal amount of exercise for maximum benefit with minimum risk in SCD individuals. Full article

Background/Objectives: Acute chest syndrome (ACS) is a frequent and potentially life-threatening complication of sickle cell disease (SCD) that often develops during hospitalization for vaso-occlusive crisis (VOC). The early identification of pediatric patients at risk remains challenging, particularly in high-prevalence settings. This study aimed to identify predictors of acute chest syndrome following vaso-occlusive crisis in children with SCD. Methods: We conducted a retrospective cohort study of children and adolescents (≤18 years) with confirmed SCD admitted for VOC to Cayenne Hospital Center, French Guiana, between January 2014 and September 2024. ACS that occurred during hospitalization or within 7 days of admission was recorded. Multivariable logistic regression was used to identify independent predictors, and model performance was assessed using receiver operating characteristic (ROC) analysis. Results: Among the 825 VOC episodes in 190 patients, 239 (29%) were complicated by ACS. Independent ACS predictors were thoracic or abdominal pain at presentation (adjusted odds ratio [aOR] 14, 95% CI 6–32, p < 0.001), prior history of ACS (aOR 7.4, 95% CI 4.5–12.1), and Hb SS or Sβ⁰ genotype (aOR 1.8, 95% CI 1.2–2.4), age > 10 years (aOR 1.6, 95% CI 1.1–2.4), male sex (aOR 1.6, 95% CI 1.1–2.4), Hydroxyurea treatment was associated with a higher risk of acute chest syndrome (aOR 8.7, 95% CI 5.2–14.5), likely reflecting greater baseline disease severity among treated patients. The probability threshold maximizing the Youden index was 0.67, corresponding to a Youden index of 0.56. At this threshold, the model had a sensitivity of 61%, a specificity of 95%, a positive predictive value of 85%, and a negative predictive value of 86%. The apparent area under the receiver operating characteristic curve was 0.87 (95% CI, 0.83–0.89). The receiver operating characteristic analysis yielded an area under the curve of 0.87, indicating good apparent discrimination. Conclusions: These findings support targeted monitoring and early preventive strategies during pediatric VOC admissions. Full article

Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis, primarily driven by red blood cell lysis. Its pathophysiology is centered, though not exclusively, on the increased release of intracellular components, such as hemoglobin degradation products, which are known to stimulate innate immune responses and promote prothrombotic states. Current therapies alleviate symptoms, yet patients remain exposed to a chronic inflammatory milieu punctuated by episodes of acute pain. The recurrence of these crises can be life-threatening due to ischemia–reperfusion injury, hypercoagulability, and respiratory complications. Central mechanisms are marked by elevated hemolysis, heightened inflammatory signaling, and increased procoagulant activity, largely driven by soluble molecules released into the plasma, such as hemoglobin, nuclear molecules and other products. These compounds are recognized from sensors on immune and endothelial cells, named Pattern Recognition Receptors (PRRs), and constitute canonical pathways for intracellular activation. Four main types have been extensively studied in the literature over recent years in both infectious and sterile inflammatory contexts; still, only a few have elucidated the mechanisms underlying acute and chronic inflammation in patients with SCA. Although Toll receptors were shown to be major in triggering immunity, other receptors were found to be important regarding this function, which suggested a multifactorial mechanism for this triggering. Therefore, here, we propose a comprehensive review of previously published findings regarding the expression, activation, and dynamics of Toll-like, NOD-like, and RIG-I–like receptors in the progression of SCA and its associated inflammatory features. Full article

Background and Clinical Significance: Sickle cell vaso-occlusive crisis (VOC) may present with severe refractory pain that is difficult to control despite guideline-directed multimodal therapy and high-dose opioids. Case Presentation: We report an adult with VOC and severe, opioid-refractory anterior thigh and leg pain who was treated with bilateral, ultrasound-guided continuous femoral nerve catheters (0.5% bupivacaine bolus per side followed by infusion of 0.2% ropivacaine at 5 mL/h each). Twenty-four-hour opioid use decreased by 76% from 44 mg intravenous hydromorphone (880 MME) before block placement to 10.4 mg (208 MME) after catheter initiation. Pain scores declined significantly from 10/10 to 3/10, facilitating mobilization and expediting discharge of the patient. No local anesthetic systemic toxicity occurred, and transient quadriceps weakness was managed with fall-risk precautions. IRB approval for this case report was waived per our institution policy. Conclusions: In select adults with VOC and predominant anterior thigh/leg pain, bilateral continuous femoral nerve catheters may provide rapid analgesia and substantial opioid-sparing benefits as part of multidisciplinary care. These findings are hypothesis-generating and support prospective evaluation of continuous peripheral nerve block strategies in VOC. Full article

Background/Objectives: Non-typhoidal Salmonella (NTS) species are well-recognized causes of invasive infection in patients with sickle cell disease (SCD), with a particular predilection for the musculoskeletal system. Although Salmonella osteomyelitis is well described in this population, septic arthritis is uncommon, especially involving the shoulder joint. We describe a case of NTS bacteremia complicated by native shoulder septic arthritis in a patient with SCD and review its clinical implications. Methods: We report the clinical course, diagnostic evaluation, microbiologic findings, imaging studies, and management of a 22-year-old man with homozygous SCD who presented with a vaso-occlusive pain crisis and subsequently developed severe sepsis with persistent Salmonella enterica bacteremia following ingestion of undercooked poultry. Persistent bacteremia prompted further evaluation for metastatic infection using advanced imaging and diagnostic arthrocentesis. Results: Whole-body imaging identified septic arthritis of the native right shoulder, which was confirmed by synovial fluid cultures growing Salmonella species. The patient underwent arthroscopic irrigation and debridement for source control. Antimicrobial therapy was narrowed to intravenous ceftriaxone based on susceptibility data and continued for six weeks. The patient demonstrated clinical improvement with resolution of bacteremia and was discharged to rehabilitation to complete therapy. Conclusions: This case highlights the importance of a careful exposure history, including foodborne sources, in patients with SCD presenting with invasive Salmonella infection. Persistent bacteremia should prompt early investigation for metastatic foci, and timely surgical source control combined with targeted antimicrobial therapy is essential for optimal outcomes in this population. Full article

Background/Objectives: This study aimed to estimate the proportion of pediatric emergency admissions related to sickle cell disease. Methods: This is a cross-sectional study. The data were collected over a period of 9 years, from 1 January 2014 to 31 December 2022. Results: We recorded 858 emergency department visits related to sickle cell disease out of a total of 135,000 pediatric emergency department visits, giving a prevalence of 6.4 per 1000 children aged up to 18 years. The median age was 12 years (8–16) years. The average waiting time in the emergency department for children with sickle cell disease was 2 h (±1) in 2014 and 45 min (±15) in 2022. Children with sickle cell anemia were more likely than others to have been seen by a consultant in an emergency department. The most commonly associated pathology was asthma, with a frequency of 17%. The risk factors for hospitalization were an age between 5 and 10 years and a severe form of sickle cell disease. Conclusions: The treatment of pain and fever were often delayed. This leads us to suggest that systematic prior communication between the pediatric hematologist and the emergency physician is crucial. However, there is a need to define best practices for the management of children with sickle cell disease presenting to the emergency department with a fever. Full article

Background: Sickle cell disease (SCD) is a rare autosomal recessive disorder that is common in countries with consanguineous marriages. It leads to various complications, including painful episodes, infections, delayed growth, stroke, and organ damage, which contribute to high healthcare utilization and costs. In Saudi Arabia, the prevalence of SCD is notably high, largely due to the frequency of consanguineous marriages. However, there has not yet been a study estimating the direct medical costs of managing SCD based on real-world data. This study aims to assess these costs in Saudi Arabia. Methods: Data were collected from electronic medical records (EMRs) at a university-affiliated tertiary care center. A micro-costing approach was used to estimate the direct medical costs (e.g., laboratory tests, imaging, emergency department visits, hospitalizations, prescription medications, outpatient visits, etc.) retrospectively over a 12-month follow-up period. The baseline characteristics of the patients were presented using frequencies and percentages. The costs of different healthcare services were analyzed using means and the 95% confidence intervals. A generalized linear model (GLM) with a gamma distribution was utilized to examine the association between the overall costs and patient characteristics (e.g., age, gender, duration of illness, surgeries, blood transfusions, etc.), allowing for the estimation of the adjusted mean costs. Results: A total of 100 patients met the inclusion criteria and were included in the analysis. The mean age of the patients was 10.21 years (±6.87 years); 53% were male, and a substantial majority (96%) had the HbSS genotype. Sixty-one percent of the patients had undergone at least one red blood cell (RBC) exchange transfusion, while 21% had undergone surgical procedures, including tonsillectomy, splenectomy, and cholecystectomy. Additionally, 45% had experienced at least one vaso-occlusive crisis (VOC), and 59% had been hospitalized at least once in the past 12 months. Factors such as the frequency of laboratory tests and imaging studies, the length of hospital stay (LOS), the rate of emergency department (ED) visits, surgical procedures, the number of prescription medications, and the frequency of blood transfusions were all significant predictors of higher direct medical costs (p < 0.05). The estimated mean annual direct medical costs per patient were USD 26,626.45 (95% CI: USD 22,716.89–USD 30,536.00). After adjusting for various factors, including age, gender, duration of illness, frequency of lab and imaging tests, LOS, ED visits, surgical procedures, number of prescription medications, rates of VOCs, and RBC exchange transfusions, the adjusted mean annual direct medical cost per patient was calculated to be USD 14,604.72 (95% CI: USD 10,943.49–USD 19,525.96). Conclusions: The results of this study emphasize the substantial direct medical costs linked to sickle cell disease (SCD), which are greatly affected by the frequency of related complications. These insights should motivate policymakers and healthcare researchers to assess both the national direct and indirect costs associated with SCD, especially given the significant number of SCD patients in Saudi Arabia. Full article

Acute cardiovascular disorders are incriminated in up to 33% of maternal deaths, and the presence of sickle cell anemia (SCA) aggravates the risk of peripartum complications. Herein, we present a 24-year-old Caribbean woman with known SCA who developed a vaso-occlusive crisis at 36 weeks of gestation that required emergency Cesarean section. In the early postpartum period, she experienced fever with rapid onset of acute respiratory distress in the context of COVID-19 infection that required tracheal intubation and mechanical ventilatory support with broad-spectrum antibiotics and blood exchange transfusion. Shortly thereafter, transthoracic echocardiography documented severe biventricular dysfunction associated with raising levels of cardiac troponin and ECG signs of myocardial ischemia. Medical treatment with incremental dobutamine and noradrenaline infusion failed to improve cardiac output and blood gas exchange. After consultation with the regional cardiac center, a prompt decision was made to provide cardiac and respiratory support via implantation of femoral cannula and initiation of veno-arterial extracorporeal membrane oxygenation (ECMO, Cardiohelp^®). Under stable ECMO, the patient was transferred by helicopter to a specialized cardiac center. There were no signs of ongoing hemolysis, and progressive recovery of the right and left ventricular function facilitated forward blood flow through the aortic valve. Three days after implantation, ECMO was weaned, and the cannula were removed. One day later, the patient’s chest X-rays showed partial resolution of lung edema. The patient was successfully extubated, and non-invasive ventilation with pulmonary rehabilitation was initiated to speed up her functional recovery. Full article

Hematological emergencies are critical medical conditions that require immediate attention due to their rapid progression and life-threatening nature. As various examples, hypercalcemia, often associated with cancers such as multiple myeloma, can lead to severe neurological and cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis and multiorgan failure. Sickle cell crisis, a common complication in sickle cell disease, results from vaso-occlusion, leading to acute pain and tissue ischemia. Tumor lysis syndrome, reported in cases of rapid destruction of cancer cells, causes electrolyte imbalances and acute kidney injury. Acute transfusion reactions, fundamental in hematological conditions, can range from mild allergic responses to severe hemolysis and shock, requiring prompt management. Disseminated intravascular coagulation, involving excessive coagulation and bleeding, is commonly triggered by hematological malignancies, common in the first phases of acute promyelocytic leukemia. Recently, in the era of bispecific antibodies and chimeric antigen receptor T cells, cytokine release syndrome is a manifestation that must be recognized and promptly treated. Understanding the pathophysiology, recognizing the clinical manifestations, and ensuring adequate diagnostic strategies and management approaches for each condition are central to early intervention in improving patient outcomes and reducing mortality. Full article

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life. Full article

Background and Objectives: In sickle cell disease (SCD), hepatopathy is a cumulative consequence of ischemia/reperfusion (I/R) injury from a vaso-occlusive crisis, tissue inflammation, and iron overload due to blood transfusion. Hepatopathy is a major contributing factor of shortened life span in SCD patients. We hypothesized that the voxelotor, a hemoglobin allosteric modifier, ameliorates sickle hepatopathy. Materials and Methods: Townes SCD mice and their controls were treated with either chow containing GBT1118, a voxelotor analog, or normal chow. We evaluated inflammation, fibrosis, apoptosis and ferroptosis in their livers using qPCR, ELISA, histology, and immunohistochemistry. Results: GBT1118 treatment resulted in reduced hemolysis, iron overload and inflammation in the liver of SCD mice. There were significant reductions in the liver enzyme levels and bile acids. Furthermore, GBT1118-treated mice exhibited reduced apoptosis, necrosis, and fibrosis. Increased ferroptosis as evident from elevated 4-hydroxynonenal (4-HNE) staining, malondialdehyde (MDA) levels, and expression of Ptgs2 and Slc7a11 mRNAs, were also significantly reduced after GBT1118 treatment. To explain the increased ferroptosis, we evaluated iron homeostasis markers in livers. SCD mice showed decreased expression of heme oxygenase-1, ferritin, hepcidin, and ferroportin mRNA levels. GBT1118 treatment significantly increased expressions of these genes. Conclusions: Our results suggest GBT1118 treatment in SCD confers the amelioration of sickle hepatopathy by reducing inflammation, fibrosis, apoptosis, iron overload and ferroptosis. Full article

Sickle cell disease (SCD) is the most common hemoglobinopathy in the world. Sickle cell vaso-occlusive episodes (VOEs) are very painful acute events and the most common complication as well as reason for hospitalization. SCD pain is best evaluated holistically with a pain functional assessment to aid in focusing pain management on reducing pain in addition to improving function. Patients with SCD have long endured structural racism and negative implicit bias surrounding the management of pain. Thus, it is important to approach the management of inpatient pain systematically with the use of multi-modal medications and nonpharmacologic treatments. Furthermore, equitable pain management care can be better achieved with standardized pain plans for an entire system and individualized pain plans for patients who fall outside the scope of the standardized pain plans. In this article, we discuss the best practices to manage SCD VOEs during an inpatient hospitalization. Full article

Background/Objectives: Sickle cell disease (SCD) impacts about 100,000 people in the US. SCD increases the risk of cholelithiasis and microvascular ischemia, which could increase the risk of acute pancreatitis (AP). Abdominal pain is a common presenting symptom of AP and sickle cell vaso-occlusive crisis. The purpose of our systematic review is to estimate the prevalence and determine the severity of AP in individuals with SCD compared to the general population. Methods: Multiple electronic databases were searched. We included studies that included children and adults (population) and addressed the association of SCD (exposure) with AP (outcome) compared to the same population without SCD (control). Two authors screened titles and abstracts independently, and data were abstracted in duplication from included studies. We registered this protocol in PROSPERO-CRD42023422397. Results: Out of 296 studies screened from multiple electronic databases, we identified 33 studies. These studies included 17 case reports, one case series, and 15 retrospective cohort studies, and 18 studies included children. Eight of the AP case reports were in patients with HbSS genotype, two with sickle beta thalassemia, and one with HbSoArab, and in six case reports, a genotype was not specified. Complications were reported in 11 cases—respiratory complication (in at least four cases), splenic complications (three cases), pancreatic pseudocyst (two cases) and death from AP (one case). Of the four AP cases in the case series, three had HbSS genotype, and two cases had complications and severe pancreatitis. AP prevalence in SCD was estimated to be 2% and 7% in two retrospective studies, but they lacked a comparison group. In retrospective studies that evaluated the etiology of AP in children, biliary disease caused mostly by SCD was present in approximately 12% and 34%, respectively. Conclusions: Data on the prevalence of AP in individuals with SCD are limited. Prospectively designed studies aiming to proactively evaluate AP in individuals with SCD who present with abdominal pain are needed to improve timely diagnosis of AP in SCD and outcomes. Full article

Sickle cell disease is an orphan disease affecting ethnic minorities and characterized by profound systemic manifestations. Although around 100,000 individuals with SCD are living in the US, the exact number of individuals is unknown, and it is considered an orphan disease. This single-gene disorder leads to red blood cell sickling and the deoxygenation of hemoglobin, resulting in hemolysis. SCD is associated with acute complications such as vaso-occlusive crisis, infections, and chronic target organ complications such as pulmonary disease and renal failure. While genetic therapy holds promise to alter the fundamental disease process, the major challenge in the field remains the target end organ damage and ways to mitigate or reverse it. Here, we provide an overview of the clinical manifestations and pathogenesis with a focus on end-organ damage and current therapeutic options, including recent FDA-approved stem cell and gene editing therapies. Full article

Background/Objectives: This study investigated vaso-occlusive crises (VOCs) in sickle cell disease in Lubumbashi, Democratic Republic of Congo, aiming to understand the disease complexities amidst limited resources. With sickle cell hemoglobinopathies on the rise in sub-Saharan Africa, this nine-year study explored factors associated with VOCs and hematological components. Methods: This study comprised 838 patients, analyzing VOCs and hematological changes over time. Demographic characteristics and blood composition changes were carefully categorized. A total of 2910 crises were observed and managed, with analyses conducted on severity, localization, and age groups using statistical methods. Results: The majority of crises were mild or moderate, primarily affecting osteoarticular regions. Statistical analysis revealed significant disparities in crisis intensity based on location and age. The association between blood samples and the number of comorbidities was investigated. Significant positive associations were found for all parameters, except monocytes, indicating a potential link between blood variables and complication burden. Survival analysis using Cox regression was performed to predict the probability of experiencing a second crisis. No significant effects of medication or localization were observed. However, intensity (p < 0.001), age (p < 0.001), and gender (p < 0.001) showed significant effects. Adjusted Hazard Ratios indicated increased risk with age and male gender and reduced risk with mild or severe crisis intensity compared to light. Conclusions: This research sheds light on the complexities of VOCs in resource-limited settings where sickle cell disease is prevalent. The intricate interplay between clinical, laboratory, and treatment factors is highlighted, offering insights for improved patient care. It aims to raise awareness of patient challenges and provide valuable information for targeted interventions to alleviate their burden. Full article