Association of Sickle Cell Trait with Risk and Mortality of COVID-19: Results from the United Kingdom Biobank.

Sickle cell trait (SCT) carriers inherit one copy of the Glu6Val mutation in the hemoglobin gene and is particularly common in Black individuals (5-10%). Considering the roles of hemoglobin in immune responses and the higher risk for coronavirus disease (COVID-19) among Black individuals, we tested whether Black SCT carriers were at increased risk for COVID-19 infection and mortality according to the United Kingdom Biobank. Among Black individuals who were tested for COVID-19, we found similar infection rates among SCT carriers (14/72; 19.7%) and noncarriers (167/791; 21.1%), but higher COVID-19 mortality rates among SCT carriers (4/14; 28.6%) than among noncarriers (21/167; 12.6%) (odds ratio [OR], 3.04; 95% confidence interval [CI], 0.69-11.82; P = 0.12). Notably, SCT carriers with preexisting diabetes had significantly higher COVID-19 mortality (4/4; 100%) than those without diabetes (0/10; 0%; (OR, 90.71; 95% CI, 5.66-infinite; P = 0.0005). These findings suggest that Black SCT carriers with preexisting diabetes are at disproportionally higher risk for COVID-19 mortality. Confirmation by larger studies is warranted.

Serious adverse events in African-American cancer patients with sickle cell trait and inherited haemoglobinopathies in a SEER-Medicare claims cohort.

African-American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA-; 144,863 NHW-). AA+ patients had significantly increased risk for ≥1 AEs compared to AA- (RR = 1.19; 95% CI 1.11-1.27) and NHW- (RR = 1.23; 95% CI 1.15-1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.

Sickle cell trait: what are the costs and benefits of screening?

INTRODUCTION: Eight percent of African Americans are carriers of the sickle cell trait. Some regard this as a benign anomaly, but others point to incidents of sudden exercise-related death, calling for a preliminary screening of either all athletes or those of African-American ancestry. This brief review considers the costs and benefits of such screening. EVIDENCE ACQUISITION: The Ovid/Health Star data-base was searched from 1996 to June 2015. 2014. The terms "exercise", "exercise therapy", "sports", "athletes", "physical activity/motor activity" and "physical fitness" were combined to yield 227,120 citations. Likewise, the terms "sickle cell trait", "sickle cell disease", "splenic infarction", "hemoglobin S" and "rhabdomyolysis" identified 12,325 citations. A combination of the 2 searches yielded 416 abstracts. EVIDENCE SYNTHESIS: Excluding items relating to animal research or forms of rhabdomyolysis other than sickling left 375 abstracts; 115 papers merited full examination. This material covered the risks of sickle cell trait and of screening (55 items), effects upon physical performance (31 items), cellular mechanisms (23 items), nutrition (4 items), and other topics (2 items). Supplemented material was drawn from reference lists and personal files. The tendency to sickling was provoked by excessive exercise relative to physical condition in hot or hypoxic conditions, and by local tissue acidosis, conditions that were best avoided by all athletes. The condition had little impact upon physical performance, but the relative risks of heat illness, exertional rhabdomyolysis, splenic infarction and sudden death were all increased by the sickle cell trait. The absolute number of critical incidents was nevertheless small, calling for close assessment of the costs and putative benefits of widespread screening. CONCLUSIONS: Sports physicians should be aware of the clinical picture of sickling and be prepared to treat it. Screening may be cost-effective if targeted to black athletes involved in certain sports, although it has yet to be demonstrated how far the diagnosis of sickle cell trait reduces the risk of death when exercising in an adverse environment. A better tactic may be to reduce risks for all competitors by educating athletes and their coaches to adopt an intensity of training appropriate to the individual's physical condition, to maintain full hydration, and to avoid exposure to excessive heat and hypoxia.

Sickle cell trait associated with a RR of death of 37 times in National Collegiate Athletic Association football athletes: a database with 2 million athlete-years as the denominator.

BACKGROUND: This study examines sickle cell trait (SCT) as a cause of sudden death in National Collegiate Athletic Association (NCAA) athletes and explores the cost-effectiveness of different screening models. METHODS: The authors reviewed the cause of all cases of sudden death in NCAA student-athletes from January 2004 through December 2008. The authors also explored the cost-effectiveness of screening for this condition in selected populations assuming that identifying athletes with SCT would prevent death. RESULTS: There were 273 deaths and a total of 1 969 663 athlete-participant-years. Five (2%) deaths were associated with SCT. In football athletes, there were 72 (26%) deaths. Of these, 52 (72%) were due to trauma unrelated to sports activity and 20 (28%) were due to medical causes; nine deaths were cardiac (45%), five were associated with SCT (25%). Thirteen of the 20 deaths due to medical causes occurred during exertion; cardiac (6, 46%) SCT associated (5, 39%), and heat stroke unrelated to SCT (2, 15%). All deaths associated with SCT occurred in black Division I football athletes. The risk of exertional death in Division I football players with SCT was 1:827 which was 37 times higher than in athletes without SCT. The cost per case identified varied widely depending on the population screened and the price of the screening test. CONCLUSIONS: Exertional death in athletes with SCT occurs at a higher rate than previously appreciated. More research is needed to (1) understand the pathophysiology of death in SCT-positive athletes and (2) determine whether screening high-risk populations reduces mortality.

[Assessment of the use of transfusion therapy and complications in orthopedic surgery in patients with sickle-cell anemia: retrospective study]. / Analyse des pratiques transfusionnelles et complications chez le patient drépanocytaire en situation de chirurgie orthopédique: étude rétrospective.

Red blood cells (RBCs) transfusion is a common practice in the treatment or for the prevention of complications of patients with sickle-cell disease. In surgery, pre-operative transfusions are frequently given to prevent peri-operative complications. There is no consensus however on the best regimen of transfusion for this purpose. The transfusion techniques are muliple. In addition, pre-operative transfusion therapy is reported to be largely responsible for an increased morbidity and mortality in patients with sickle cell anemia undergoing surgery. During the period 1990-2000, 16 patients (4 men and 12 women) with a mean age of 37 years and various major sickle cell hemoglobinopathies underwent 32 total hip arthroplasty for femoral head necrosis. Nine patients with sickle-cell trait were included as control group. Twelve of them had haemoglobin SS (HbSS), 2/16 had HbSC, 2/16 had HbS/betathalassemia. Operative transfusion were given in only 12/32 procedures, 4 were performed pre-operatively and 8 intra-operatively. Simple transfusion (mean: 2.5 packed red cells) were administered in all the procedures. The main complications observed in our patients were anemia by hemolysis and haemorrhagic shock, vaso-occlusive crisis and chest syndrome. Anemia requiring transfusions was significatively related to the procedures with pre-operative transfusion. In the light of our result, we would like to propose transfusional protocol--if needed--only intra-operatively.

Anterior pituitary gland assessment in sickle cell anaemia patients with delayed menarche.

Pituitary gland dysfunction and its contribution to menarcheal delay in sickle cell anaemia patients was investigated. Ten SS patients mean age 17.5 years who had not achieved menarche were recruited and 10 each of AS and AA controls, mean ages 17.4 and 17.7 years were used as controls to study the effect of the heterozygous state. Dynamic studies with LHRH and TRH were performed for 60 minutes and LH, FSH, PRL and TSH assays were done. Median basal values were significantly lower in the SS patients compared with the AS and AA controls for LH, FSH and PRL. LH: 3.0; 7.1; 7.7 U/L, FSH: 2.1: 4.3: 5.1 U/L. PRL: 94.5; 590; 390 U/L, respectively. The median basal TSH values did not show any significant difference between the SS subjects (7.3 U/L) and the AS and AA controls (5.4 U/L) and 5.6 U/L, respectively. The readily releasable pool also showed the same pattern for LH, FSH and PRL as the basal values while the SS subjects had higher median TSH releasable pool values that were significantly different from those of the AA controls. From the prolactin responses three subjects demonstrated maturational delay in menarcheal achievement while seven demonstrated isolated gonadotrophin deficiency. It is concluded that SS patients with delayed menarche have a hypothalamopituitary axis dysfunction that gives rise to delay in menarcheal achievement and metabolic adaptations to stress of illness. The heterozygous state did not delay menarcheal onset.

[Echocardiographic assessment of patients with sickle cell anemia]. / Evaluación ecocardiográfica de pacientes con anemia falciforme.

One hundred and sixty four (164) patients were evaluated. Sixty (60) with Sickle cell disease (SSHg.) and ninety seven (97) with Trait (ASHg.); seventeen (17) were normal control group. The study confirmed that the incidence of cardiomyopathy in Trait (ASHg.) is greater than reported by other clinical investigations. Cardiac arrhythmia, atrial fibrillation, premature ventricular contractions, bundle branch blocks, and T and ST modifications with sub epicardial isquemia were most significant electrocardiographics changes. The possibility of myocardial infarction in SS patients with low or normal hemoglobin is significant. M-Mode and 2-D echo, demonstrated similar end diastolic volumes in AS and SS patients in which cardiomyopathy were diagnosticated. Patients with cardiac failure, treated with cardiotonics, diuretics and ACE were compensated most frequently. To prevent hemosiderosis, antioxydant (alfatocoferol and Ubiquinones) were used with satisfactory response.