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.

Prevalence of sickle cell trait and needs assessment for uptake of sickle cell screening among secondary school students in Kampala City, Uganda.

BACKGROUND: Sickle cell disease (SCD) is one of the most frequent and traumatizing genetic disease in Uganda, with the prevalence of the sickle cell trait (SCT) estimated at 13.3% leading to serious psycho-social and economic impact on the patients and their families. AIM: This study aimed to determine the burden of SCT and factors influencing the uptake of screening services among secondary school students in Uganda. METHODS: We used an analytical cross-sectional design with a multi-stage sampling approach. A total of 399 students from four secondary schools in Kampala City were enrolled in this study. Data were gathered using semi-structured questionnaires and blood screening. We used the sickling test to determine the presence of sickle cell alleles among the participants and hemoglobin electrophoresis as a confirmatory test. Data gathered using the questionnaire were analyzed using descriptive and inferential statistics. RESULTS: In total, 5.8% of participants who were tested during this study had SCT. Most (80.2%) participants were not in an intimate relationship at the time of data collection. The majority (60.4%) had moderate knowledge about SCT screening and obtained information about screening from the school. Only 29 (7.3%) participants knew of a family member with sickle cell. Overall, participants had a negative attitude toward SCT screening (67%), although 41.6% believed that most people who were sickle cell carriers did not live long and were often sick. Statistically significant associations were found between testing for SCT and knowing a partner's sickle cell status (odds ratio [OR] 2.112, p = 0.043) and Anglican religion (OR 2.075, p = 0.047). CONCLUSION: Despite the moderate level of knowledge and negative attitudes, a relatively large number of participants had SCT. This highlights the need for a comprehensive health education package targeting adolescents to promote SCD/SCT screening.

COVID-19 Infection and Outcomes in Newborn Screening Cohorts of Sickle Cell Trait and Sickle Cell Disease in Michigan and Georgia.

The sickle cell mutation increases morbidity in those with sickle cell disease (SCD) and potentially sickle cell trait, impacting pulmonary, coagulation, renal, and other systems that are implicated in COVID-19 severity. There are no population-based registries for hemoglobinopathies, and they are not tracked in COVID-19 testing. We used COVID-19 test data from 2 states linked to newborn screening data to estimate COVID outcomes in people with SCD or trait compared with normal hemoglobin. We linked historical newborn screening data to COVID-19 tests, hospitalization, and mortality data and modeled the odds of hospitalization and mortality. Georgia's cohort aged 0 to 12 years; Michigan's, 0 to 33 years. Over 8% of those in Michigan were linked to positive COVID-19 results, and 4% in Georgia. Those with SCD showed significantly higher rates of COVID-19 hospitalization than the normal hemoglobin Black cohort, and Michigan had higher rates of mortality as well. Outcomes among those with the trait did not differ significantly from the normal hemoglobin Black group. People with SCD are at increased risk of COVID-19-related hospitalization and mortality and are encouraged to be vaccinated and avoid infection. Persons with the trait were not at higher risk of COVID-related severe outcomes.

Reconsidering sickle cell trait testing of red blood cell units allocated to children with sickle cell disease.

BACKGROUND: Sickle cell trait (SCT) testing of red blood cell (RBC) units is sometimes performed to identify and divert units containing hemoglobin S (HbS). Recipients strategically guarded against this exposure include fetuses, neonates, and children with sickle cell disease (SCD). The clinical necessity of this practice is unclear. STUDY DESIGN AND METHODS: A one-year audit (2018) was performed at a pediatric tertiary care hospital that tests for SCT in RBC units prescribed to children with SCD and neonates. The impact of incorporating varying numbers of SCT RBC units in a single-unit top-up, partial-manual red cell exchange, and automated erythrocytapheresis was modeled in four typical-parameter age scenarios (2, 5, 10, and 18 years) sharing a high baseline HbS. Additionally, a survey assessing SCT testing practices was administered to Canadian pediatric hospital transfusion laboratories serving hemoglobinopathy programs. RESULTS: Of 2268 donor RBC units tested, one was positive for SCT (0.04% [95% CI: 0.01%-0.24%]), at a cost of $19,384.56 CAD. The impact of SCT unit incorporation on lost HbS reduction was modest (Δ1%-3% [automated erythrocytapheresis] and Δ4%-15% [top-up/partial manual exchange]). The survey (with all 13 sites responding) showed variable SCT testing practice; four (31%) do not test, four (31%) test for children with SCD, and six (46%) test for neonates. CONCLUSION: RBC SCT testing may be more costly than beneficial or necessary in children with SCD. As of 2019, our transfusion service has ceased SCT testing for this population. Further research in the fetal/neonatal populations is needed to overturn this entrenched practice.

Sickle cell trait screening in students in a Ugandan university: a cross-sectional study.

OBJECTIVE: To determine the uptake, knowledge level and attitude towards sickle cell trait screening in students aged 18 to 35 years in a Ugandan university. METHODS: This was a university-based, cross-sectional study of students aged 18 to 35 years who were students at the Busitema University Faculty of Health Sciences. We used a simple random sampling technique to recruit participants. We conducted multivariable logistic regression to establish the association between factors such as age, year of study, marital status and uptake of sickle cell trait screening (SCTS) services. RESULTS: A total of 315 students participated in the study. The uptake rate of SCTS was 24.4%. The knowledge level regarding sickle cell disease/SCTS was 93.7%, and 73.3% of respondents had a positive attitude towards SCTS, with a mean score of 23.32 ± 5.84. A multivariate analysis showed that those aged 25 to 29 years were 7.8 times more likely to have SCTS, while married respondents were 1.3 times more likely to be screened. CONCLUSION: The uptake of SCTS services was low relative to the total number of participants recruited in this study. Therefore, the uptake of SCTS needs to be encouraged in students at universities.

National Audit of Criteria For Pre-Operative Sickle Cell Screening in Children.

Aim We set out to identify the current practice in the anaesthesiology departments of Ireland's public hospitals that deliver paediatric anaesthesia with regard to pre-operative screening for sickle cell disease (SCD) and Sickle cell trait (SCT). Methods The Departments of Anaesthesiology at 14 public HSE-funded hospitals that deliver paediatric anaesthesia were contacted over a three month period in 2020. Any existing policies regarding pre-operative screening of paediatric patients for Sickle cell disease or trait were sought. Comparisons were made between any screening policies in place. Results A response was received from 11 of the 14 hospitals. Three out of 11 of the Anaesthesiology Departments have formal policies in place. The ethnicities identified for pre-operative screening varied across these three hospitals. Conclusion Despite a significant increase in the number of people of African, middle Eastern & Indian descent living in Ireland in recent years, no neonatal screening programme for Sickle cell exists here, and no national policy exists with criteria to guide the practice of pre-operative screening of patients for SCD/SCT (trait). Our survey highlights a lack of standardisation in the approach to pre-operative sickle cell screening of children across Ireland's public hospital system. In view of the increasing multiculturalism in Ireland we recommend a national review of the merits of the introduction of developing a targeted national guideline for pre-operative screening for sickle cell in at-risk children.

Optical absorbance-based rapid test for the detection of sickle cell trait and sickle cell disease at the point-of-care.

People afflicted with sickle cell disease (SCD) experience severe deterioration in quality of life. The disease is characterized by debilitating pain, anemia, and increased susceptibility to life threatening infections. This genetic disorder is endemic to many parts of the world. Extensive and accurate screening of individuals with sickle cell trait (SCT) in the population, coupled with genetic counselling can inhibit the propagation of the disease. The gold-standard techniques for the detection of sickle hemoglobin, such as capillary electrophoresis, HPLC, and genetic testing, are prohibitively expensive and time-consuming. Mass screening is usually conducted with a low-cost test called the solubility test, which does not offer high specificity. This study proposes a game-changing single-step low-cost method for rapidly yet accurately screening and diagnosing SCD and SCT. This method relies on the hitherto unexplored differences in the optical absorbance between diseased, trait, and normal blood samples, under deoxygenated conditions. The proposed method was tested in two phases of clinical validation: a pilot study and a blind study. A total of 438 patient samples were tested using the proposed method across the two phases. The proposed method offers an average accuracy, sensitivity, and specificity of 97.6%, 96.9%, and 98.6%, respectively. The proposed test has the potential to obliviate the conventional two-step process of screening and diagnostic tests as it can be used at the point-of-care with minimal training and yet yield results reliable enough to assess disability benefit claims.

Parents' Experiences and Needs Regarding Infant Sickle Cell Trait Results.

BACKGROUND AND OBJECTIVE: Sickle cell trait (SCT) has reproductive implications and can rarely cause health problems. SCT counseling improves parent knowledge but is infrequently received by children with SCT compared with children with cystic fibrosis carrier status. There are no national guidelines on SCT disclosure timing, frequency, or counseling content. Parents' experiences with SCT disclosure and counseling are poorly understood but could inform the development of guidelines. We explored parents' experiences with and desires for SCT disclosure and counseling for their infants with SCT identified via newborn screening. METHODS: Parents of infants 2 to 12 months old with SCT were recruited through a state newborn screening program for semistructured interviews to explore their experiences with and desires for SCT disclosure and counseling. Inductive thematic analysis was conducted. RESULTS: Sixteen interviews were completed from January to August 2020. Most parents reported that SCT disclosure occurred soon after birth, in person, and by the child's physician. Five themes were identified: parent knowledge before child's SCT disclosure, family planning, the dynamics of SCT disclosure and counseling, emotions and actions after SCT disclosure, and parent desires for the SCT disclosure and counseling process. Two primary parent desires were revealed. Parents want more information about SCT, particularly rare symptomatology, and they want SCT counseling repeated once the child approaches adolescence. CONCLUSION: Parents report receiving their child's SCT diagnosis in the early newborn period from their child's doctor but indicate they receive incomplete information. Opportunities exist in primary care pediatrics to better align SCT disclosure timing and counseling content with parent desires.

Sudden Death in Diabetic Ketoacidosis Complicated by Sickle Cell Trait.

ABSTRACT: In a sudden death investigation of a service member with sickle cell trait (SCT), evidence of sickle cell crisis further complicated by coexisting, undiagnosed diabetic ketoacidosis called into question the synergistic effects of diabetic ketoacidosis on red blood cell sickling. Sickle cell trait affects more than 4 million people in the United States (US) with the highest prevalence in non-Hispanic Blacks (7%-9%; Mil Med 2017;182(3):e1819-e1824). The heterozygous state of sickled hemoglobin was previously considered a benign condition causing sickling during hypoxic, high-stress conditions such as exercise and high altitude ( Am Assoc Clin Chem 2017). However, research within the last decade shows evidence of sudden death among SCT patients ( J Forensic Sci 2011;56(5):1352-1360). It has been shown that the presence of sickled hemoglobin artificially lowers levels of hemoglobin A1c making it a less effective biomarker for red blood cell glycosylation over time in sickle cell patients ( JAMA 2017;317(5):507-515). The limited scope of medical understanding of the effects of SCT in combination with other comorbidities requires further investigation and better diagnostic criteria. The uniqueness of the US Military and its screening program for sickle cell disease (SCD) and SCT allows for more detection. Since May 2006, newborn screening for SCD/SCT has been a national requirement; however, anyone older than 14 years may not know their SCD/SCT status ( Semin Perinatol 2010;34(2):134-44). The previous absence of such national screening makes it more challenging to identify SCT and SCD patients even within high-risk populations. Furthermore, patients may not know or understand the results of their SCD/SCT status testing. International standards for the autopsy of decedents with SCD and SCT exist ( R Coll Pathol 2017). Within the US, testing of vitreous electrolytes is a common practice in suspected natural death cases, but a review of the US literature did not demonstrate any autopsy standards or recommendations for persons with SCT or high-risk persons for sickling pathologies. The identification of a new diagnosis of type 2 diabetes mellitus, as the cause of death, is not uncommon; however, this case indicates that type 2 diabetes mellitus was not the sole contributing factor. It further illustrates that the US may be underestimating the impact of SCD and SCT as a cause of death, a contributing factor to death, and its synergistic effects with other pathologic processes. We propose a stringent literature review in conjunction with a review of international autopsy standards to develop national autopsy standards and possible SCT/SCD screening recommendations for high-risk persons at the time of autopsy.

Sudden Death in High School Athletes: A Case Series Examining the Influence of Sickle Cell Trait.

ABSTRACT: Athletes with sickle cell trait (SCT) have up to a 37-fold increased risk of exercise-related death. Exertional collapse associated with sickle cell trait (ECAST) is uncommon but can lead to exercise-related death due to exertional sickling. We present a case series of fatal ECAST in high school athletes aged 14 to 16 years. All 3 athletes experienced collapse during practice sessions with muscle pain or weakness. Upon evaluation at the hospital, the athletes had a significant metabolic acidosis that did not respond as expected to fluid resuscitation. Admitting diagnoses for the athletes included exertional heat stroke or dehydration. All 3 athletes had profound rhabdomyolysis leading to acute renal failure, worsening metabolic acidosis, and hyperkalemia. They rapidly progressed to disseminated intravascular coagulation, multiorgan system failure, and death. The autopsies of all 3 athletes showed extensive sickle cell vaso-occlusion involving the spleen liver, and muscles. Final clinical and pathologic diagnosis supported ECAST with fatal exertional rhabdomyolysis. Exertional collapse associated with sickle cell trait is an uncommon but potentially deadly condition that is often underrecognized or misdiagnosed as exertional heat stroke. The development of ECAST is thought to be multifactorial with exercise intensity, recent illness, and exercising conditions (ie, heat and altitude). Prevention should be the primary goal for athletes with SCT through exercise modification, education of precipitation factors, and cessation of exercise with recent illness. Athletes with suspected ECAST should undergo aggressive resuscitation with a low threshold for early transfer to a tertiary care facility for further management and potential hemodialysis.

Newborn Screening and Clinical Profile of Children With Sickle Cell Disease in a Tribal Area of Gujarat.

OBJECTIVE: To present the result of newborn sickle cell disease (SCD) screening and clinical profile of SCD newborns in a tribal area of Gujarat. METHODS: We screened all newborns of sickle cell trait (SCT) and SCD mothers for SCD using high-performance liquid chromatography (HPLC) within two days of birth at a secondary care hospital in a tribal area in Gujarat from 2014 to 2019. Newborns with SCD were registered under an information technology based platform for hospital-based comprehensive care. Neonates were followed prospectively every 3 months. If they missed the clinic visit, a medical counsellor visited them at home to collect the required information. RESULTS: Out of 2492 newborns screened, 87 (3.5%) were diagnosed with SCD. Among the 67 newborns screened for alpha-thalassemia deletion, 64 (95.4%) of babies had alpha-thalassemia deletion. We recorded total 554 clinic visits over the period of 221.5 person-years. The rates of acute febrile illness, painful crisis, hospitalization and severe anemia were 42.9, 14.9, 14.9 and 4.5 per 100 person-year, respectively. Two deaths were recorded, and 5 babies (5.7%) had severe SCD. CONCLUSION: We found a high prevalence of alpha thalassemia deletion among newborn SCD cohort in tribal area of Gujarat, and 70% babies had atleast one clinical complication on follow-up.

Community based screening for sickle haemoglobin among pregnant women in Benue State, Nigeria: I-Care-to-Know, a Healthy Beginning Initiative.

BACKGROUND: Haemoglobin genotype screening at prenatal care offers women an opportunity to be aware of their genotype, receive education on sickle cell disease (SCD) and may increase maternal demand for SCD newborn screening. In developed countries, most pregnant women who access prenatal care and deliver at the hospital receive haemoglobin genotype screening. In settings with low prenatal care attendance and low hospital deliveries, community-based screening may provide similar opportunity for pregnant women. We assessed the feasibility and acceptability of integrating haemoglobin genotype screening into an existing community-based HIV program. METHODS: Onsite community-based integrated testing for HIV, hepatitis B virus and haemoglobin electrophoresis, were conducted for pregnant women and their male partners. Community Health Advisors implementing the NIH and PEPFAR-supported Healthy Beginning Initiative (HBI) program provided education on SCD, collected blood sample for haemoglobin electrophoresis and provided test results to participants enrolled into the HBI program. We concurrently conducted a cross-sectional study using a pretested, semi-structured, interviewer administered questionnaire to collect demographic data and assess awareness of individual haemoglobin "genotype" among HBI pregnant women participants. RESULTS: In this study, 99.9% (10,167/10,168) of pregnant women who received education on SCD accepted and completed the survey, had blood drawn for haemoglobin electrophoresis and received their results. A majority of participating pregnant women (97.0%) were not aware of their haemoglobin "genotype". Among the participants who were incorrect about their haemoglobin "genotype", 41.1% (23/56) of women who reported their haemoglobin "genotype" as AA were actually AS. The odds of haemoglobin "genotype" awareness was higher among participants who were in younger age group, completed tertiary education, had less number of pregnancies, and attended antenatal care. Overall prevalence of sickle cell trait (AS) was 18.7%. CONCLUSIONS: It is feasible to integrate haemoglobin "genotype" testing into an existing community-based maternal-child program. Most pregnant women who were unaware of their haemoglobin "genotype" accepted and had haemoglobin genotype testing, and received their test results. Increasing parental awareness of their own haemoglobin "genotype" could increase their likelihood of accepting newborn screening for SCD.

An investigation of sickle cell trait, body mass index, and fitness in relation to venous thromboembolism among African American adults.

BACKGROUND: The relationships of sickle cell trait (SCT), body mass index (BMI), and physical fitness to venous thromboembolism (VTE) in young adults have received little attention. OBJECTIVES: To test for associations among SCT, BMI, fitness, and VTE. PATIENTS/METHODS: We conducted a retrospective cohort study of 48,316 SCT-tested, African American individuals in the US Army during 2011-14. We used Cox proportional hazards models to compute adjusted hazards of deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with selected factors. RESULTS: Incidence rates of DVT and PE were 1.09 and 0.91 cases per 1000 person-years, respectively. Adjusted hazard ratios (aHRs) for DVT for men and women with SCT were 0.9 (95% confidence interval [CI]: 0.4-2.0; P = .711) and 1.51 (CI: 0.7-3.2; P = .274), respectively. aHRs for PE for SCT+ men and women were 1.1 (CI: 0.5-2.4; P = .773) and 1.2 (CI: 0.5-3.1; P = .650), respectively. Low physical fitness was associated with DVT and PE in women (DVT aHR =3.1; CI: 1.4-6.5; P = .004; PE aHR =4.6; CI: 2.1-9.9; P < .001) and DVT in men (aHR =2.2; CI: 1.0-4.6; P = .048). Recent weight gain of 1 or more BMI points was associated with DVT in men (aHR =1.8; CI: 1.1-2.8; P = .017). CONCLUSIONS: We found no evidence of increased VTE risk associated with SCT in this population. However, lower fitness levels and BMI increases were so associated.

Fluorescence spectroscopy as a novel technique for premarital screening of sickle cell disorders.

Spectral diagnostic screening for sickle cell disease was carried out on volunteer blood samples (N = 100). The samples were subjected to different diagnostic methods including conventional complete blood count (CBC), hemoglobin electrophoresis (HBE) and spectral diagnosis. For the spectral diagnostic method, we discriminated three different characteristic spectral features. In total, 15 samples were sickle cell trait (SCT), 34 samples were sickle cell disease (SCD), and the rest of the samples (N = 51) were normal controls. The spectral discrimination of the three different sets of samples was distinguished on the quantification of fluorescent biomolecules such as tyrosine, tryptophan, NADH, FAD, and porphyrins. The results were compared with the conventional standard CBC and capillary electrophoresis findings. The spectral diagnosis method exhibited a sensitivity and specificity greater than 90 % for the tested samples. This technique requires only 5 mL blood samples, has an analysis time of 20 min, exhibits high accuracy and may be used in small clinics in remote villages.

Screening of blood donors for sickle cell trait using a DNA-based approach: Frequency in a multiethnic donor population.

BACKGROUND: Minority RBC donors are important to support the transfusion needs of patients with sickle cell disease. Testing of donors for sickle cell trait (SCT) is performed to avoid transfusion of hemoglobin S+ (HbS+) RBCs to specific patient groups and to investigate leukoreduction failures. A screening assay based on hemoglobin solubility is commonly used. The purpose of this study was to validate a DNA approach for HbS screening. METHODS: Hemoglobin solubility screening (Pacific Hemostasis or SICKLEDEX) and PreciseType human erythrocyte antigen (HEA)-HbS (Immucor) targeting c.20A>T in the ß-globin gene were performed according to manufacturer's directions. Resolution of differences in results included gene sequencing and high-performance liquid chromatography (HPLC). RESULTS: Initial validation of HEA-HbS performed by testing 60 known samples, 20 HbS/A, A/A, and S/S, gave expected results. However, in the subsequent parallel testing phase, 4/58 samples HbS+ by solubility assay tested negative by HEA-HbS; the negative results were confirmed by ß-globin gene sequencing. Samples from donors self-identifying as White testing HbS+ by solubility assay (n = 60) were retested by HEA-HbS and HPLC. The HEA-HbS assay was concordant with HPLC which is recognized as the gold standard for hemoglobin variation. CONCLUSION: A DNA-based approach is an alternative to screen donors for SCT, found in approximately 7% of Black and 1.7% of our random donors. HEA-HbS correlated with HPLC results in all samples tested, supporting the use of HEA-HbS as the test of record. The method allows higher throughput screening and testing at the donor center allows association of the screening result with the donor record to avoid repeat testing.

Atypical Presentations of Exertional Collapse.

ABSTRACT: Exertional collapse associated with sickle trait (ECAST) is an underrecognized cause of exertional collapse triggered by complex mechanisms involving acidosis, rhabdomyolysis, and arrhythmias, all of which create sickling, vaso-occlusive problems, and ultimately end organ failure. Three cases are described in young athletes, as well as 12 other examples of ECAST noted in case reports and news sources. Exertional collapse associated with sickle trait can be differentiated from other common causes of collapse (exertional heat syndrome, acute cardiac events, and asthma) because it is a conscious collapse without neurological changes, occurs early in workout with only mildly elevated body temperature, and involves muscle pain and weakness but not cramping. Aggressive early management and transport to care facilities can reverse ECAST in certain cases. This article discusses tips for early recognition, initial treatment in the emergency department, and precautions that can be taken to prevent sickling collapse in athletes with sickle cell trait (SCT).