Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-ß) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease's clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Mortality related to sickle cell disease and COVID-19 in Brazil, 2020.

OBJECTIVE: The ability to cause death is the definitive measure of an infectious disease severity, particularly one caused by a novel pathogen like severe acute respiratory syndrome-CoV-2 (COVID-19). This study describes sickle cell disease-related mortality issues during the COVID-19 pandemic in Brazil. METHODS: The provisional 2020 mortality data originated from the public databases of the Mortality Information System and were investigated using the multiple-cause-of-death methodology. RESULTS: In 2020, 688 sickle cell disease-related deaths occurred, of which 422 (61.3%) had an underlying cause of death and 266 (38.7%) had an associated cause of death. Furthermore, 98 COVID-19-related deaths occurred, of which 78 were underlying cause of death among sickle cell disease associated (non-underlying) cause of death. Sickle cell disease-related deaths occurred mostly among young adults aged 25-49 years. COVID-19 deaths occurred at ages older than among sickle cell disease-related deaths. Majority of deaths happened in the southeast (42.3%) and northeast regions (34.0%), while COVID-19 deaths prevailed in the northeast region (42.9%). Regarding overall deaths, the leading underlying cause of death was sickle cell disease itself, followed by infectious and parasitic diseases (14.8%), owing to COVID-19 deaths, and diseases of the circulatory system (8.9%). Next, in males, diseases of the digestive system (4.8%) occurred, while, in females, maternal deaths succeeded, included in the chapter on pregnancy, childbirth, and the puerperium, accounting for 5.9% of female deaths. The leading overall associated (non-underlying) cause of deaths were septicemias (29.4%), followed by respiratory failure (20.9%), pneumonias (18.3%), and renal failure (14.7%). CONCLUSION: In Brazil, COVID-19 deaths produced trend changes in sickle cell disease-related causes of death, age at death, and regional distribution of deaths in 2020.

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.

Unswitched memory B cell deficiency in children with sickle cell disease and response to pneumococcal polysaccharide vaccine.

Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen. We hypothesized that asplenia in SCD is associated with alterations in the peripheral blood lymphocyte population and explored whether UMBC deficiency was associated with a clinical phenotype. We analyzed B cell subsets and clinical history for 238 children with SCD and 63 controls. The median proportion of UMBCs was lower in children with SCD compared with controls (4.7% vs. 6.6%, p < .001). Naïve B cells were higher in SCD compared with controls (80.6 vs. 76.3%, respectively, p = .02). UMBC frequency declined by 3.4% per year increase in age in SCD (95% CI: 2%, 4.7%, p < .001), but not in controls. A majority of children in all cohorts had an IgM concentration in the normal range for age and there were no differences between groups (p = .13). Subjects developed titers adequate for long-term protection to fewer serotypes in the polysaccharide vaccine than controls (14.7 vs. 19.4, p < .001). In this cohort, bacteremia was rare and specific clinical complications were not associated with UMBC proportion. In summary, UMBC deficiency occurs in SCD and is associated with age. Future studies should investigate B cell subsets prospectively and identify the mechanism of B cell loss in the spleen.

Reversibility of Cognitive Deficits and Functional Connectivity With Transfusion in Children With Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: People with sickle cell disease (SCD) are at risk of cognitive dysfunction independent of stroke. Diminished functional connectivity in select large-scale networks and white matter integrity reflect the neurologic consequences of SCD. Because chronic transfusion therapy is neuroprotective in preventing stroke and strengthening executive function abilities in people with SCD, we hypothesized that red blood cell (RBC) transfusion facilitates the acute reversal of disruptions in functional connectivity while white matter integrity remains unaffected. METHODS: Children with SCD receiving chronic transfusion therapy underwent a brain MRI measuring white matter integrity with diffusion tensor imaging and resting-state functional connectivity within 3 days before and after transfusion of RBCs. Cognitive assessments with the NIH Toolbox were acquired after transfusion and then immediately before the following transfusion cycle. RESULTS: Sixteen children with a median age of 12.5 years were included. Global assessments of functional connectivity using homotopy (p = 0.234) or modularity (p = 0.796) did not differ with transfusion. Functional connectivity within the frontoparietal network significantly strengthened after transfusion (median intranetwork Z-score 0.21 [0.17-0.30] before transfusion, 0.29 [0.20-0.36] after transfusion, p < 0.001), while there was not a significant change seen within the sensory motor, visual, auditory, default mode, dorsal attention, or cingulo-opercular networks. Corresponding to the change within the frontoparietal network, there was a significant improvement in executive function abilities after transfusion (median executive function composite score 87.7 [81.3-90.7] before transfusion, 90.3 [84.3-93.7] after transfusion, p = 0.021). Participants with stronger connectivity in the frontoparietal network before transfusion had a significantly greater improvement in the executive function composite score with transfusion (r = 0.565, 95% CI 0.020-0.851, p = 0.044). While functional connectivity and executive abilities strengthened with transfusion, there was not a significant change in white matter integrity as assessed by fractional anisotropy and mean diffusivity within 16 white matter tracts or globally with tract-based spatial statistics. DISCUSSION: Strengthening of functional connectivity with concomitant improvement in executive function abilities with transfusion suggests that functional connectivity MRI could be used as a biomarker for acutely reversible neurocognitive injury as novel therapeutics are developed for people with SCD.

Managing gastrointestinal challenges: Diarrhea in sickle cell anemia.

Sickle cell anemia (SCA), a hereditary hemoglobinopathy, is characterized by the presence of abnormal hemoglobin and has long been associated with a wide range of complications. While much attention has been given to the condition hematological aspects, gastrointestinal complications, particularly diarrhea, have been relatively understudied and often overlooked. This publication delves into the management of gastrointestinal challenges, with a focus on diarrhea, in individuals living with SCA. The pathophysiology of SCA is intrinsically linked to gastrointestinal complications, and diarrhea is a common manifestation of this condition. This abstract publication outlines the key elements discussed in the full-length work, which includes the clinical presentation of diarrhea in these patients, the diagnostic tools used to evaluate the condition, and various management strategies to alleviate symptoms and enhance the overall quality of life for affected individuals. The paper emphasizes the importance of patient education, offering healthcare professionals valuable insights into how to inform and support patients in managing their conditions effectively. It also highlights the need for continued research to further our understanding of gastrointestinal challenges in SCA and to identify potential areas for future therapeutic interventions. Ultimately, the comprehensive management of diarrhea in individuals with SCA is vital for their overall well-being. This publication serves as a valuable resource for healthcare providers, researchers, and caregivers in addressing the gastrointestinal challenges that accompany SCA, ultimately working toward a better quality of life for those affected by this condition.

Genetic Variants Associated with the Risk of Stroke in Sickle Cell Anemia: Systematic Review and Meta-Analysis.

Sickle cell anemia (SCA) is the most common cause of stroke in children. As it is a rare disease, studies investigating the association with complications like stroke in SCD have small sample sizes. Here, we performed a systematic review and meta-analysis of the studies exploring an association of genetic variants with stroke to get a better indication of their association with stroke. PubMed and Google Scholar were searched to identify studies that had performed an association analysis of genetic variants for the risk of stroke in SCA patients. After screening of eligible studies, summary statistics of association analysis with stroke and other general information were extracted. Meta-analysis was performed using the fixed effect method on the tool METAL and forest plots were plotted using the R program. The random effect model was performed as a sensitivity analysis for loci where significant heterogeneity was observed. 407 studies were identified using the search term and after screening 37 studies that cumulatively analyzed 11,373 SCA patients were included. These 37 studies included a total of 2,222 SCA patients with stroke, predominantly included individuals of African ancestry (N = 16). Three of these studies performed whole exome sequencing while 35 performed single nucleotide-based genotyping. Though the studies reported association with 132 loci, meta-analyses could be performed only for 12 loci that had data from two or more studies. After meta-analysis we observed that four loci were significantly associated with risk for stroke: -α3.7 kb Alpha-thalassemia deletion (P = 0.00000027), rs489347-TEK (P = 0.00081), rs2238432-ADCY9 (P = 0.00085), rs11853426-ANXA2 (P = 0.0034), and rs1800629-TNF (P = 0.0003396). Ethnic representation of regions with a high prevalence of SCD like the Mediterranean basin and India needs to be improved for genetic studies on associated complications like stroke. Larger genome-wide collaborative studies on SCD and associated complications including stroke need to be performed.

Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

PURPOSE: To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). MATERIAL AND METHODS: This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6 months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. RESULTS: The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05 g/dL vs. 6.31 g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. CONCLUSION: PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones. METHODS: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI. Participants with a history of overt stroke were excluded. Infarct masks were manually delineated on T2-fluid-attenuated inversion-recovery MRI and registered to the Montreal Neurological Institute 152 brain atlas to generate an infarct heatmap. Border zone regions between anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA) were quantified using the Digital 3D Brain MRI Arterial Territories Atlas, and logistic regression was applied to identify relationships between infarct distribution, demographics, and stroke risk factors. RESULTS: Of 113 participants with SCD (median age 26.1 years, interquartile range [IQR] 21.6-31.4 years, 51% male), 56 (49.6%) had SCIs. Participants had a median of 5.5 infarcts (IQR 3.2-13.8). Analysis of infarct distribution showed that 350 of 644 infarcts (54.3%) were in 4 border zones of CBF and 294 (45.6%) were in non-border zone territories. More than 90% of infarcts were in 3 regions: the non-border zone ACA and MCA territories and the ACA-MCA border zone. Logistic regression showed that older participants have an increased chance of infarcts in the MCA territory (odds ratio [OR] 1.08; 95% CI 1.03-1.13; p = 0.001) and a decreased chance of infarcts in the ACA-MCA border zone (OR 0.94; 95% CI 0.90-0.97; p < 0.001). The presence of at least 1 stroke risk factor did not predict SCI location in any model. DISCUSSION: When compared with children with SCD, in adults with SCD, older age is associated with expanded zones of tissue infarction that stretch beyond the traditional border zones of CBF, with more than 45% of infarcts in non-border zone regions.

Prevalence and predictors of iron deficiency anaemia among children with sickle cell disease in Dodoma, Tanzania: a cross-sectional study.

BACKGROUND: Patients with sickle cell disease (SCD) are prone to iron profile derangements. This study aimed to determine the prevalence of iron deficiency anaemia (IDA) and their predictors among children with SCD aged between 6 months and 14 years. Assessment of the prevalence of IDA and its predictors helps to understand ways of alleviating the magnitude of the problem so as to prevent possible complications such as shortness of breath and chest pain. METHODS: This was a cross-sectional analytical hospital-based study which included 174 patients with SCD attending SCD clinics at St. Gema hospital and Dodoma regional referral hospital in Dodoma city from October 2020 to March 2021. The cut-off points for detection of IDA was serum ferritin level < 30 µg/L and low mean corpuscular volume (MCV) for age. Data were analyzed using SPSS software version 25.0. Multivariate logistic regression analysis was used to determine the predictors of IDA. P-value less than 0.05 was considered significant. RESULTS: The prevalence of IDA in this study was (16.1%, n = 28). Family income of less than 70,000/= TZS/month (AOR = 2.2, 95% CI = 1.07-2.49, p = 0.023), being transfused with blood less than 3 times from the time of being diagnosed with SCD (AOR = 5.5, 95% CI = 1.03-8.91, p = 0.046), and eating red meat at least once per month (AOR = 3.60, 95% CI = 1.37-9.46, p = 0.010) remained the independent predictors of IDA in multivariate regression analysis. CONCLUSION: The findings of this study have shown that, support of families with children suffering from SCD in terms of financial support for improving medical services including optimal blood transfusion and affordability of diet which is rich in iron such as red meat is imperative.

Poor Sleep Quality in Jamaican Adults With Sickle Cell Disease: Prevalence, Risk Factors, and Association With Quality of Life.

Poor sleep and chronic illnesses have a bidirectional relationship where presence of one can worsen the other. Sickle cell disease (SCD) is associated with significant morbidity and early mortality. In this study, we examine sleep quality, its predictors, and its association with quality of life in Jamaican adults with SCD. This cross-sectional study evaluated 177 well adult SCD patients for sleep quality using The Pittsburgh Sleep Quality Index (PSQI) and quality of life using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Multiple linear regression models examined the predictors of poor sleep quality. The mean global PSQI score was 6.9 (SD 4.2) with 56.5% having poor sleep quality. Women had significantly worse scores for sleep efficiency (p 0.005), sleep latency (p 0.03) and higher use of sleeping medications (p 0.02). Those overweight/obese had significantly worse subjective sleep quality (p 0.001) and sleep efficiency (p 0.05). In multivariate regression analysis, overweight individuals had poorer sleep quality (OR: 2.9; 95% C.I.: 1.07, 7.88) than those with normal weight whereas those unemployed and looking for a job had lower prevalence of poor sleep quality (OR 0.2; 95% C.I.: 0.05, 0.77) compared to employed individuals. Participants with good sleep quality had significantly better functioning in all 5 domains of the ASCQ-Me. In conclusion, persons with SCD who are overweight or obese are at increased risk of poor sleep which can negatively affect quality of life. Patient populations and healthcare providers will need to manage the emerging burden of overweight/obesity.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Sickle Cell Disease Phenotypes and Obstructive Sleep Apnea; Are They Related?

OBJECTIVE: This study aims to compare the polysomnographic features between Arab-Indian and Benin phenotypes of sickle cell disease (SCD). MATERIALS AND METHODS: This prospective cross-sectional study was conducted in the Children's Hospital at King Fahad MedicalCity, in Riyadhwhere childrenwere recruited fromthe pediatric hematology clinic and pediatric sleepmedicine. All families were approached and patients who met the inclusion criteria and agreed to participate were included in the study. RESULTS: Eighty four children (37 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.65, 11) years and their body mass index z score was -1.45 (-2.195, -1.45). The evidence of obstructive sleep apnea (OSA) was more prominent in the Benin phenotype (66.7%) in comparison to those of the Arab-Indian (35.2%) phenotype ( p = 0.006). Additionally, 56.7% of Benin had moderate to severe OSA whereas Arab-Indian had 18% with a ( p = 0.0003). Controlling for other factors, the odds ratio (confidence interval) of having OSA in Benin phenotype was 4.68 (1.42-15.38) times higher as compared to Arab-Indian phenotype. CONCLUSION: The risk of having OSA as well as the severity of OSA is higher in Benin phenotype as compared to Arab-Indian phenotype which indicates the presence of potential OSA risk factors other than the SCD itself.

Optimization of single-needle red cell exchange in patients with sickle cell disease.

The hypercoagulable state associated with sickle cell disease (SCD) can be challenging for apheresis procedures. Among 62 single-needle red cell exchanges (SN-RCEs) performed over a 15-month period, 4 patients experienced 6 hemolytic events with a discolored plasma layer, elevated plasma/RBC interface in the centrifuge, and accompanying alarms of "Cells were detected in plasma line from centrifuge" or "AIM system detected RBC at top of connector." The hemolysis originated from the apheresis instrument because samples from the apheresis belt but not the patients' peripheral blood were positive for hemolysis. Further analysis showed the alarms occurred more often in SN-RCEs (20.4%) than double-needle RCEs (2.7%), and the hemolysis was probably secondary to clumping. To optimize SN-RCE, we increased the anticoagulant dosage by changing Inlet/AC ratio from 13 to 8 and lowered the inlet rate to the level comparable to double-needle RCE. The adjustments were well-tolerated with no more hemolysis.

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.

Validating evidence for the knowledge, management and involvement of dentists in a dental approach to sickle-cell disease.

This study validated the content of an instrument designed to assess the knowledge, involvement (attitudes) and management (practice) of dentists relative to sickle-cell disease (KAPD-SCD). The instrument consisted of five domains composed of a total of thirteen items: I. Dentist's self-assessment relative to sickle-cell disease; II. Dentist's knowledge of the repercussions of sickle-cell disease on the stomatognathic system; III. Dentist's knowledge of the complications of sickle-cell disease in the stomatognathic system; IV. Dentist's knowledge concerning the dental management of sickle-cell disease patients; and V. Dentist's involvement in an approach to sickle-cell disease. Twelve experts assigned scores to each item of the instrument. The criteria were clarity, understanding and appropriateness, leaving open fields for comments. Descriptive and content analyses of the data were made. Each expert analyzed 39 assessment units. The percentages considered for agreement were high (>80%), medium (70%-80%), or low (<70%), and each item was maintained or revised according to the percentage observed. There was high consensus in 74% of the assessment units (the corresponding items were maintained), medium consensus in 24% of them (the corresponding items were revised), and disagreement in 2% of them, namely as regards the "appropriateness" of item 5 ("Are there oral complications in sickle-cell disease?"), which was revised. The final version of the instrument had 16 items for different applications such as in the clinical care program, teaching program, or research program, with different cut-off scores for each application. In conclusion, the level of agreement among experts showed evidence of the content validity of the instrument.

Assessment of hypoxemia among young adults with sickle cell anaemia in steady state in southwestern Nigeria: a crosssectional study.

OBJECTIVES: Hypoxia is a known feature of sickle cell anaemia (SCA) which results from chronic anaemia and recurrent vaso-occlusive crisis (VOC) which can cause tissue ischaemia that leads to an end organ damage. The hallmark of SCA is chronic anaemia and recurrent vaso-occlusive crisis. The aim of this study is to compare the oxygen saturation of sickle cell anaemic individuals with the normal haemoglobin type (Hb AA) control and also to determine the prevalence of hypoxemia among SCA. RESULTS: Two-hundred and twenty-two (136 Hb SS and 86 Hb AA) participated in the study. The mean ± SD of age (years), oxygen saturation (%) and pulse rate (bpm) of participants with sickle cell anaemia and Hb AA control were 21.85 ± 3.04 and 22.14 ± 3.18 (t = 0.701, p = 0.436), 95.21 ± 3.02 and 98.07 ± 0.81 (t=-8.598, p < 0.0001) and 77.10 ± 9.28 and 73.16 ± 8.52 (t = 3.173, p = 0.002) respectively. The prevalence of hypoxemia among SCA participants was 47.1%. Prevalence of hypoxemia in males with SCA was 60.9% while 39.1% of the females had hypoxemia.

Management of diabetes mellitus patients with sickle cell anemia: Challenges and therapeutic approaches.

The coexistence of diabetes mellitus (DM) and sickle cell anemia (SCA) poses significant challenges in clinical management due to the complex interactions and overlapping complications associated with both conditions. Managing diabetes in individuals with SCA requires a comprehensive approach that addresses the unique physiological and pathological aspects of both diseases. This paper reviews the challenges encountered in the management of DM in patients with SCA and explores therapeutic strategies and approaches to optimize patient care. Challenges in the management of DM in individuals with SCA stem from several factors, including the impact of hemoglobin variants on glycemic control assessment, increased susceptibility to infections, altered immune response, and complications associated with both diseases. Moreover, the coexistence of SCA and DM heightens the susceptibility to infections due to compromised immune function, emphasizing the need for vigilant preventive measures, including vaccinations and close monitoring for infectious complications. Close collaboration among healthcare providers specializing in diabetes, hematology, and other relevant fields is crucial for developing comprehensive care plans. Individualized treatment strategies that balance glycemic control, pain management, and preventive care are essential to mitigate complications and optimize the overall health outcomes of patients with both DM and SCA. In conclusion, managing diabetes in the context of SCA necessitates a nuanced and patient-centered approach. By addressing the challenges and employing tailored therapeutic strategies, healthcare providers can improve the quality of life and health outcomes for individuals affected by both conditions.

Sickle Cell Disease Related Vasculopathies and Early Evaluation in a Pediatric Population.

BACKGROUND/AIM: Cardiovascular pathologies are ubiquitous in sickle cell disease (SCD). A targeted literature review was conducted to compare the overall epidemiology of selected vasculopathies seen in SCD (SCDVs) compared to the general population. Since many SCDV may originate in childhood, the study also focused on the retrospective investigation of SCDVs in a pediatric cohort at the Harbor-UCLA Medical Center. PATIENTS AND METHODS: SCDVs were studied along patient age, ß-globin genotypes, and fetal hemoglobin (HbF). Urine microalbumin/creatinine ratios (UM/Cr), trans-cranial doppler (TCD) and tricuspid regurgitant jet velocities (TRJV) were analyzed as well. Retinographies and overt vasculopathies were presented descriptively. RESULTS: Among 20 females and 20 males [average 8.3 years (2.3-19 years)], 70% had HbSS/Sß0, 22.5% HbSC and 7.5%-HbSß+. The mean(±SD) HbF% was 17.4±12.7% (30% higher in <10 vs. ≥10 y/o, and 3 times higher in SS/Sß0). Twenty-six patients received hydroxyurea and 13/26, L-glutamine. Thirty-six patients had TCDs within 1.4±0.9 years and all laboratory values were obtained within the last 12 months. TCDs showed low-normal velocities, but 2 were higher for HbSS/Sß0 vs. HbSC/Sß+ (MCA-96 vs. 86 cm/s, p=0.03; and PCA-50 vs. 41, p<0.001). Nineteen of 28 patients with echocardiograms had measurable TRJV (2.46±0.19 m/s); 9 had TRJV ≥2.5-2.8 m/s, but BNP ≤80 pg/ml. SS/Sß0 was associated with higher UM/Cr. There were 2 cases with silent infarcts, 1-Moyamoya, 2-persistent macroalbuminuria, and 1-hematuria/renal papillary necrosis. Most ≥9 y/o patients had retinographies without SCD-related changes. There was no correlation among TCD (MCA), TRJV, and UM/Cr (n=17); thus, in this subpopulation, pathologies of cerebral, cardiopulmonary, and renal vasculatures evolved independently. Patients with higher TRJV and/or overt vasculopathy (n=14) were older than ones without (12.5±4.7 vs. 6.1±3.1 y/o, p<0.001), and had lower HbF (11.4±7.6 vs. 20.6±13.8%, p=0.026). CONCLUSION: While overt SCDVs are less frequent in children, age-dependent trends/surrogate markers suggest their early origination in youth, justifying intense screening to prevent their progression with disease-modifying measures.