Immunization adherence among children with sickle cell disease and sickle cell trait: Results of a population-based study.

INTRODUCTION: Despite the importance of timely vaccine completion for protection from infectious disease, there is limited knowledge of the immunization adherence rates of children with sickle cell disease (SCD). METHODS: This is a retrospective cohort study comparing the immunization rates of children with SCD to those with sickle cell trait between 2008 and 2019 in Georgia. Completion rates for each vaccine and the proportion of children with up-to-date status at 24 and 35 months were calculated and compared between the cohorts. Chi-square tests with odds ratios (OR) for differences and 95% confidence intervals (CIs) were reported on the overall up-to-date rates and rates for individual vaccines at 24 and 35 months for the two cohorts. RESULTS: Children with SCD had higher up-to-date rates than children with sickle cell trait at 24 and 35 months. At 35 months, the overall up-to-date rates (OR = 1.17; 95% CI, 1.04-1.31; p = .004) and the four-dose pneumococcal conjugate vaccine series (OR = 1.36; 95% CI, 1.18-1.57; p < .001) were significantly different between the groups. Both cohorts had the highest completion rates for the hepatitis B series and the lowest rates for the varicella vaccine. Doses of diphtheria, tetanus, and acellular pertussis vaccine; varicella; and pneumococcal conjugate vaccines were most commonly missed by children in both cohorts. CONCLUSIONS: Children with SCD have better immunization coverage than children with sickle cell trait, but there is an opportunity for improvement. Policymakers and healthcare professionals should focus on increasing access to care coordination services among children with SCD to ensure on-time and preventive healthcare services.

The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study.

Purpose: To evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). Design: Population-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 health care organizations worldwide. Participants: Diabetes mellitus patients (type 1 [T1DM] or 2 [T2DM]), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or sickle-cell/hemoglobin-C; (2) DM with SCD; and (3) DM with SCT. Methods: All patients with DM were categorized into 3 cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome Measures: Risk of DR in DM patients with and without SCD or SCT. Results: There was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable twofold increased risk for T1-proliferative DR (PDR) (relative risk [RR]: 2.03; 95% confidence interval [CI]: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher PDR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-PDR was also found to be higher in patients with SCT. Conclusions: The risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for PDR in patients with SCT and T1DM. This indicates there may be a potential role of sickle-cell disorders in diabetic eye disease progression. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

[SMARCB1-deficient renal medullary carcinoma with supra clavicular revealing location]. / Carcinome médullaire rénal SMARCB1-déficient révélé par une métastase ganglionnaire sus-claviculaire.

We report the case of a 14 year-old teenager who has SC hemoglobinosis and presented with a tumor syndrome with a retro-peritoneal mass, a supraclavicular lymph node and a mid-renal lesion. The microscopic examination revealed an undifferentiated tumor proliferation infiltrating the lymph node parenchyma. This tumor proliferation was INI1/SMARCB1-deficient, and expressed cytokeratins. Given the fact that the histopathological data showed an undifferentiated INI1-deficient carcinoma and that the patient has a kidney lesion and a sickle cell trait, the final diagnosis was lymph node metastasis of SMARCB1-deficient renal medullary carcinoma (OMS 2022).

Update on the practice of premarital screening for sickle cell traits in Africa: a systematic review and meta-analysis.

BACKGROUND: Screening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening. METHODS: This review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits. RESULTS: Our results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53-49.11]; I2: 98.95% [98.74-99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (ß = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables. CONCLUSION: With over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools.

Comparative assessment of quality of life among adolescents with sickle cell disease and sickle cell trait: evidence from Odisha, India.

The present study aims to assess the quality of life (QOL) of adolescents with sickle cell disease (SCD) and sickle cell trait (SCT) in hard-to-reach regions in Koraput district of Odisha state. 387 adolescents with sickle cell genes (HbSS = 52, HbAS = 135, HbA = 200) were selected through their medical records from southern parts of Odisha. A validated and pretested QOL scale was modified to assess the QOL. The questionnaires were modified by aiming to describe the proportion of adolescents who feel restricted in different domains, measuring the extent within each domain, and finding an aggregate score of QOL. Furthermore, to explore the expenditure on health, 552 households were selected randomly, of which 72 families had HbS individuals. This study found a significantly lower health-related QOL in adolescents with SCD. However, most psychosocial sub-domains, for instance, worry about the illness, frequency of angry days, feeling jealousness toward other normal adolescents, and negative feelings of sadness on some days, are similarly affected in adolescents with SCT and SCD. The overall QOL of SCD individuals is more affected (percentage of affected mean score = 60.93%), followed by SCT individuals (35.63%). Healthy adolescents' QOL is relatively unaffected (13% were affected). The yearly frequency of blood transfusion received (1.7 ± 0.4) and hospitalization (2.1 ± 0.9) was significantly higher in adolescents with SCD. The healthcare expenditure was significantly higher (3.6% to 81.3% of the family income) in families with HbS than in families without HbS (0.8% to 19.2%) (p < 0.05). The overall QOL was affected in both SCD and SCT adolescents. The focus should be given equally to both SCD and SCT individuals, in spite of only SCD individuals.

Vaso-Occlusive Crises in Sickle Cell Trait Patients With Blood Loss Anemia: A Report of Two Cases.

This report of two cases confronts the longstanding perception of Sickle Cell Trait (SCT) as a clinically benign condition, highlighting its complex and severe clinical manifestations, particularly in the context of blood loss anemia and vaso-occlusive crises (VOCs). The hallmark of sickle cell disease is the severe pain caused by acute vaso-occlusion of the microvasculature that leads to bone marrow infarction. We report two cases of patients with SCT and severe anemia in the setting of blood loss secondary to uterine fibroids subsequently causing VOCs with likely bone sequestration. The occurrence of VOCs in SCT, while infrequent, can be serious and demands a high index of suspicion, particularly when patients appear in significant distress and cardiac or vascular etiologies are ruled out as a source. Reversal of anemia in this case provided quick resolution to symptoms, and we recommend other clinicians not disregard a differential of VOC in SCT carriers, and urge to treat patients as they would if they had sickle cell disease. This report challenges the conventional view of SCT as a condition of clinical benignity, calling for a recalibration in the clinical understanding, management strategies, and focus on this genetic trait under similar circumstances.

Blood count changes in malaria patients according to blood groups (ABO/Rh) and sickle cell trait.

INTRODUCTION: Introduction: Malaria continues to be the leading cause of hospitalization and death in Angola, a country in sub- Saharan Africa. In 2023, in the first quarter, 2,744,682 cases were registered, and of these 2,673 patients died due to malaria disease. Previous studies have shown that the ABO blood group can affect the progression of malaria to severe conditions after P. falciparum infection, while the sickle cell gene offers relative protection. OBJECTIVE: We investigated changes in the blood count according to blood groups (ABO/Rh) and sickle cell trait in patients with malaria in Luanda, capital of Angola. METHODOLOGY: This was a longitudinal, prospective and observational study with 198 patients hospitalized for malaria. RESULTS: Of the 198 patients studied, 13(6.6%) were ABRh(+), 4(2.0%) were ARh(-), 49(24.7%) were ARh(+), 42(21, 2%) were BRh (+), 5(2.5%) were ORh(-) and 85(42.9%) were ORh(+). For sickle cell trait, 145(73.2%) were AA, 37(18.7%) were AS and 16(8.1%) were SS. No statistical relationship was observed between age group, sex, parasitemia, clinical picture, hematocrit, MCV, HCM, MCHC, leukocytes, NEUT, LINF and PTL values with blood groups (p<0.05), but there was a relationship between values of hemoglobin and ABO/Rh blood groups (p>0.05). There was no relationship between age, parasitemia, clinical condition, MCV, HCM and MCHC values, leukocytes, NEUT and LINF with sickle cell trait (p<0.05), but there was a relationship between sex, hemoglobin and PTL and sickle cell values. sickle cell trait (p>0.05). CONCLUSION: It is imperative to differentiate patients with malaria based on blood groups and sickle cell trait, taking into account mainly the blood count parameters that demonstrate that there are patients who, depending on blood group or sickle cell trait, may react weakly to malaria infection regardless of the degree of parasitemia and medical prognosis.

Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants' demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.

Early-onset indicators of a hypercoagulable state and clinical complications in a cohort of children with sickle cell trait.

Adults with sickle cell trait (SCT) have a procoagulant state with increased risk of thromboembolism, but limited data are available for children. We compared the coagulation profile of children with SCT, different sickle cell disease (SCD) genotypes, and healthy controls. Compared to controls and similarly to HbSC patients, 41 SCT children (mean age 6.85 years; 20 males; 88% Africans) had a characteristic procoagulant profile: higher levels of factor VIII, von Willebrand factor (VWF) Ag and CBA, D-dimer; lower levels of ADAMTS 13 activity, ADAMTS13 activity: VWFAg, plasminogen activator inhibitor, tissue plasminogen activator. Moreover, 13/41 had clinical complications of SCD, five requiring hospitalization.

A Rare Presentation of Extramedullary Hematopoiesis as an Adrenal Mass: A Case Report.

Hematopoiesis is an enormous and complex process. When the primary site of hematopoiesis fails to meet the requirements of the body in conditions like hemoglobinopathies or myelofibrosis, various extramedullary sites take on the role of blood formation. Extramedullary hematopoiesis most commonly occurs in the liver, spleen, and lymph nodes and is rarely found in the thymus, heart, breast, adrenal glands, paravertebral regions, intraspinal tissue, and brain. Extramedullary hematopoiesis can mimic neoplasms in which symptoms are caused by the mass effect of the lesion. We report a rare case of a 41-year-old female patient with a fibrohematopoietic adrenal mass mimicking a neoplasm for which she underwent an adrenalectomy.

Splenic Subcapsular Hematoma from Commercial Air Travel: Case Report of a Unique Incident of Altitude-Associated Splenic Syndrome.

BACKGROUND: Sickle cell trait (SCT), the heterozygous form of sickle cell disease, is generally thought of as a benign condition. However, it is possible for those with SCT to have serious complications, especially when they are exposed to high altitudes where oxygen levels are low. CASE REPORT: We present a case of a 41-year-old man with a history of SCT who developed severe epigastric pain and nearly lost consciousness while traveling on a commercial airplane. His twin brother, who also has SCT, had a similar episode in the past and required a splenectomy. A splenic subcapsular hematoma was found in a computed tomography scan of the abdomen and pelvis with intravenous contrast. He was admitted and managed conservatively until his symptoms resolved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Though SCT is prevalent in our population, the complications that can arise, such as altitude-associated splenic syndrome, have likely not been thoroughly investigated. Physicians should add this condition to their differential if they practice at locations near airports or in areas of higher altitude and if their patients have a past medical history of SCT.

Haemoglobin Ottawa, sickle cell trait and vaso-occlusive crises.

A girl with a sickle cell trait had severe VOCs (vaso-occlusive crises), her father also had a sickle cell trait but mild VOCs, and her mother had no symptoms. Electrophoresis on agarose gel under alkaline conditions showed haemoglobin AS (HbAS) in the girl and in her father, with an S band increased more than expected (46.2% and 41.2% respectively), and a band migrating at C (16.8% and 8.9% respectively) in both. There was a band at S (19.6 %) in her mother. The C band was attributed to a hybrid tetramer with haemoglobin S (HbS) and a Hb variant. A homozygous c.46G>C mutation (Hb Ottawa, the Hb variant) was detected by Sanger sequencing in the girl. Heterozygosity for Hb Ottawa by Sanger sequencing was shown in both the father and the mother. The father, with HbAS and heterozygous for Hb Ottawa, had mild VOCs. Heterozygosity only for Hb Ottawa did not produce any abnormality in the mother. A sister and two brothers of the index patient presented a Hb variant, probably Hb Ottawa, migrating to the S zone (all 20%) at electrophoresis, without HbS. These last three were asymptomatic. We conclude that Hb Ottawa, an α-globin variant, contributes along with haemoglobin S (HbS) to VOC symptoms.

Donors with repeated blood product discards for filtration problems, clots or hemolysis: Causes and follow-up.

INTRODUCTION: Sanquin donor medicine department is informed when donations or their components are rejected. This can occur isolated or frequently. It is undesirable because the donations cannot be used and there may be an underlying medical cause. Based on regional approaches, a uniform procedure was developed. METHODS: Information about whole blood, plasma- plateletpheresis donations from which one or more components were rejected for filtration time (>2 h), hemolysis or clots were extracted from blood bank information system. After rejection of two successive components or donations or total ≥3 the donor is contacted. Depending on the medical history and investigation by the family doctor, the donor carrier is re-evaluated. We looked for the causes of the discarded products and performed a survey among blood services regarding polices with discarded products. RESULTS: One or more components from 1742 of about 2.2 million successful donations (0.08%) were rejected. The highest percentage of rejection was seen in plateletpheresis (1.5%), all for clots. No underlying medical causes were found. 24 whole blood donors were found to have sickle cell trait (SCT) and were permanently deferred. The policies for follow-up after discarded products or acceptance of SCT donors vary between the 16 blood banks. Six organizations do not follow-up donors and seven accept SCT for blood or plasma donation. CONCLUSION: Informing donors with repeated discarded products avoids the non-use of donations. Causes of repeated discarded products can be found by follow-up of donors. The results of the survey indicate a large discrepancy in policies applied worldwide.

Death due to sickle cell crisis: a case report.

Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy worldwide. It results in characteristic acute and chronic findings on postmortem computed tomography (PMCT), macroscopic and microscopic examinations. While the diagnostic imaging and macroscopic features are not specific for SCD on their own, when coupled with microscopic features such as sickled erythrocytes and evidence of chronic venous congestion (i.e., Gamna-Gandy bodies), these clues can help alert forensic pathologists to the presence of SCD. Despite the prevalence of the disease and the constellation of findings alluded to above, SCD is not often explored in forensic pathology literature. This case demonstrates classic acute and chronic features of SCD on PMCT, macroscopic and microscopic examinations. It explores the pathophysiology leading to sudden and unexpected death in a person with SCD and possible pitfalls in attribution of cause of death.

Safety of Ultrasound Contrast Agents in Pediatric Patients With Sickle Cell Disease and Trait.

Ultrasound contrast agent (UCA) use is increasing. Recent isolated reports observed a rise in pain-related adverse events with the intravenous administration of the UCA Definity in adults with sickle cell disease. To date, no studies have investigated the incidence of similar adverse events with UCA Lumason or Optison. We describe our experience regarding the safety of Lumason and Optison in children with sickle cell disease and trait who underwent contrast-enhanced ultrasound exams in our department with intravenous, intravesical, and other intracavitary routes. No pain-related or other adverse events were observed in this pediatric population with any route of UCA administration.

Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.

Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of immunoglobulin G against several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific immunoglobulin G in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs.

Sensitivity Analysis for Observational Studies with Recurrent Events.

We conduct an observational study of the effect of sickle cell trait Haemoglobin AS (HbAS) on the hazard rate of malaria fevers in children. Assuming no unmeasured confounding, there is strong evidence that HbAS reduces the rate of malarial fevers. Since this is an observational study, however, the no unmeasured confounding assumption is strong. A sensitivity analysis considers how robust a conclusion is to a potential unmeasured confounder. We propose a new sensitivity analysis method for recurrent event data and apply it to the malaria study. We find that for the causal conclusion that HbAS is protective against malarial fevers to be overturned, the hypothesized unmeasured confounder must be as influential as all but one of the measured confounders.

Delayed Plasmodium falciparum Malaria in Pregnant Patient with Sickle Cell Trait 11 Years after Exposure, Oregon, USA.

Delayed Plasmodium falciparum malaria in immigrants from disease-endemic countries is rare. Such cases pose a challenge for public health because mosquitoborne transmission must be rigorously investigated. We report a case of delayed P. falciparum malaria in a pregnant woman with sickle cell trait 11 years after immigration to the United States.

The Effectiveness of Common Interventions in the Management of Sickle Cell Disease in Primary Care Settings: A Review.

Sickle cell disease (SCD), a chronic condition that affects men and women equally, continues to present a public health burden in the United States due to its associated morbidity and complications. Despite advances in medical knowledge and the design of novel therapies for managing the disease, its burden remains compounded because of increasing rates of immigration arising from global displacements and economic unrest in many countries. We thus conducted a comprehensive literature review of publications from 2000 to 2022 to gather guidelines on managing SCD, with a search through four databases, PubMed, Embase, Google Scholar, and Cochrane; 42 articles met the final inclusion criteria after the full-text article screening process. In the United States healthcare system, primary care physicians (PCPs) are generally providers who cater to the lifelong management of chronic medical conditions, SCD not being an exception. While more SCD patients now present to primary care clinics, many PCPs still lack the confidence and adequate experience necessary to manage the condition effectively. The gap created by the shortage of PCPs extensively equipped to provide comprehensive SCD care leads to poor health outcomes for patients. It is imperative now more than ever to continue to raise awareness about this condition at the provider level, to ensure that patients receive well-rounded care to improve their quality of life and clinical outcomes. Providing up-to-date knowledge about existing and novel therapies and/or modalities of SCD treatment would undoubtedly equip the PCPs with self-assurance to manage the condition adeptly. Thus, we explore various public health interventions such as hydroxyurea therapy, pneumococcal vaccination, penicillin therapy, iron chelation therapy, and clinical decision support tools that have been implemented in primary healthcare settings and shown to be effective in improving SCD care. We also discuss recent advancements that can lead to improved outcomes for SCD patients in the future.