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.

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.

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.

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.

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.

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.

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.

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.

The association of sickle cell disorder with adverse outcomes in COVID-19 patients: A meta-analysis.

The aim is to elucidate the relationship between sickle cell disorder and severe COVID-19. We systematically searched the required articles in three electronic databases, extracting and pooling effect sizes (ES) and 95% confidence interval (CI) from each eligible study to evaluate the effect of combined sickle cell disorder on adverse consequences in patients with COVID-19. This meta-analysis included 21 studies. Sickle cell disease (SCD) was a risk factor for mortality (pooled ES = 1.70, 95% CI: 1.00-2.92, p = 0.001), hospitalization (pooled ES = 6.21, 95% CI: 3.60-10.70, p = 0.000) and intensive care unit (ICU) admission (pooled ES = 2.29, 95% CI: 1.61-3.24, p = 0.099) in COVID-19 patients. Patients with SCD had an increased risk of respiratory failure/mechanical ventilation, but a statistical association was not found (pooled ES = 1.21, 95%CI: 0.74-1.98, p = 0.036). There was significant heterogeneity between SCD and death, hospitalization, and respiratory failure/mechanical ventilation. The results of meta-regression of SCD and hospitalization suggested that the tested variables including Area (p = 0.642), study design (p = 0.739), sample size (p = 0.397), proportion of males (p = 0.708), effect type (p = 0.723), whether confounding factors are adjusted (p = 0.606) might not be the source of heterogeneity. In addition, sickle cell trait (SCT) was significantly associated with the mortality (pooled ES = 1.54, 95% CI: 1.28-1.85, p = 0.771) and hospitalization (pooled ES = 1.20, 95% CI: 1.07-1.35，p = 0.519) in patients with COVID-19. But any increased risk of ICU admission/severe (pooled ES = 1.24, 95% CI: 0.95-1.62, p = 0.520) and mechanical ventilation (OR = 1.00, 95%CI:0.59-1.69) in COVID-19 patients with SCT was not observed. Sensitivity analysis demonstrated that the results were robust. The results of the funnel plot and Egger's test did not support the existence of publication bias. Current meta-analysis indicated that sickle cell disorder has a meaningful impact on COVID-19 progression to severe cases and associated deaths. However, further investigations and research to validate the current findings is indispensable.

Systematic Literature Review Shows Gaps in Data on Global Prevalence and Birth Prevalence of Sickle Cell Disease and Sickle Cell Trait: Call for Action to Scale Up and Harmonize Data Collection.

Sickle cell disease (SCD) is an inherited monogenic disorder with high prevalence throughout sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. Sources of SCD epidemiology remain scarce and fragmented. A systematic literature review (SLR) to identify peer-reviewed studies on SCD epidemiology was performed, with a search of bibliographic databases and key conference proceedings from 1 January 2010 to 25 March 2022 (congress abstracts after 2018). The SLR followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Meta-analyses, using a binomial normal random-effects model, were performed to estimate global and regional prevalence and birth prevalence. Of 1770 journal articles and 468 abstracts screened, 115 publications met the inclusion criteria. Prevalence was highest in Africa (~800/100,000), followed by the Middle East (~200/100,000) and India (~100/100,000), in contrast to ~30/100,000 in Europe. Birth prevalence was highest in Africa (~1000/100,000) and lowest in North America (~50/100,000) and Europe (~30/100,000). This SLR confirmed that sub-Saharan and North-East Africa, India, the Middle East, and the Caribbean islands are global SCD hotspots. Publications including mortality data were sparse, and no conclusions could be drawn about mortality. The identified data were limited due to gaps in the published literature for large parts of the world population; the inconsistent reporting of SCD genotypes, diagnostic criteria, and settings; and a sparsity of peer-reviewed publications from countries with assumed high prevalence. This SLR demonstrated a lack of systematic knowledge and a need to provide uniform data collection on SCD prevalence and mortality.

Bilateral Humeral Head Avascular Necrosis: A Rare Presentation in Sickle Cell Trait.

Sickle cell disease (SCD) affects millions of people worldwide. It is an autosomal recessive hemoglobinopathy that occurs due to a point mutation in the sixth codon that replaces glutamic acid with valine in the beta-globin chain. Avascular necrosis (AVN), also known as osteonecrosis, is one of its complications. In this report, we present a case of a 25-year-old female with sickle cell trait without any comorbidities who presented to us with pain in both shoulder joints for three months and was diagnosed with AVN in bilateral shoulder joints. Appropriate treatment can dramatically reduce pain and improve the quality of life for these patients. This case drew our attention due to its rare presentation.

A Rare Case of Progressive Encephalopathy in a Sickle Cell Trait Patient: A Case Report.

Fat embolism syndrome (FES) is one of the underdiagnosed and underrecognized complications that can happen in multiple medical and surgical conditions. FES can manifest in a broad spectrum of signs and symptoms and affect multiple organ systems in the human body. One of the most commonly involved is the central nervous system (CNS), mainly the brain, which can be involved in different ways, and the presenting symptoms can vary in type and severity. One of the most common causes of FES is trauma, mainly a long bone fracture or any orthopedic injury. However, one of the rare causes of FES is sickle cell disease (SCD) and thalassemia. Generalized and vague presenting symptoms, the rarity of FES, and the absence of well-defined diagnostic criteria make it a challenging diagnosis for healthcare practitioners. FES diagnosis is usually made after having a high index of suspicion in patients with underlying risk factors that can precipitate and contribute to the pathophysiology of FES. Moreover, the diagnosis is usually reached after excluding other more common and treatable conditions.

Levels of inflammatory markers are differentially expressed in sickle cell anemia and sickle cell trait.

Although sickle cell anemia (SCA) is related to inflammation, the profile of inflammatory markers in sickle cell trait (SCT) is poorly studied. This is a cross-sectional study of inflammatory biomarkers carried out involving adults with SCA in steady state, SCT and controls. The SCA group had higher levels of lactato dehydrogenase, IL-1ß, IL-6, IL-10, and tumor necrosis factor alpha than the others, while the SCT group had similar levels to control group. In addition, SCA group had lower IL-8/IL-10 and soluble triggering receptor expressed on myeloid cells-1/IL-10 ratios. These findings indicate that individuals with SCT do not have a chronic inflammatory profile and reinforce that cytokines are involved in the maintenance of the inflammatory state in SCA.

Feasibility of peripheral blood stem cell collection from sickle cell trait donors with an intensified G-CSF regimen.

OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCD and bone marrow from an HLA-matched sibling is currently the standard of care. Haploidentical HSCT from a family donor with a TCR αß/CD19 depleted graft (T-haplo) is an increasingly successful alternative, which requires the generation of G-CSF stimulated peripheral stem cell (PBSC) from haploidentical relatives. These sickle cell trait (SCT) donors reported to develop SCD-related complications in conditions of severe stress. METHODS: In this retrospective analysis, we compared the safety and efficacy of PBSC mobilization with a G-CSF intensified mobilization regimen in SCT donors with a conventional G-CSF mobilization regimen in healthy donors. RESULTS: The reported adverse events were similar during intensified G-CSF mobilization, apheresis, and shortly after stem cell apheresis in SCT and control donors. In SCT and control donors, we were able to mobilize high yields of CD34+ stem cells and the harvested CD34+ cell count was comparable with control donors. CONCLUSIONS: Peripheral stem cell mobilization using an intensified G-CSF regimen is safe, and well tolerated among SCT donors. SCT donors are a valid alternative for collection of peripheral CD34+ stem cells for T-cell-depleted haploidentical stem cell transplantation.