Hb Genotype Research Articles

Pulmonary function assessments and clinical correlates in children with sickle cell disease in Cape Town, South Africa

Objectives: Among children with sickle cell disease (SCD) in Africa, there are varied reports on pulmonary function assessments. Restrictive pulmonary function is common in children with SCD in Africa; however, reports from Africa are few. We aimed to describe pulmonary function and its clinical correlates in children with SCD in Cape Town, South Africa. Materials and Methods: A prospective cross-sectional study was carried out over seven months from October 2018 to April 2019 in children 6–16 years with SCD. Children with hemoglobin (Hb) genotypes, homozygous for the BS globin mutation, and sickle-beta0-thalassemia Hb were included in the study. Children were excluded if they had acute complications. Medical record review clinical, laboratory, and pulmonary function assessments were done. Data were entered into Excel and exported to Stata Version 16.0 statistical software for analysis. Results: A total of 25 participants were recruited, mean (standard deviation) age of 10 ± (3.0) years. Thirteen (53%) children were under ten years and 15 (60%) were male. The median/interquartile range age at diagnosis was 1.7 [0.8–3.0] years. SCD-related complications were common. A review of the medical records showed a third of the patients (32%) had at least one previous episode of acute chest syndrome, 20 (80%) had a history of vaso-occlusive crisis, and 15 (76%) had required at least one blood transfusion. Spirometry was performed on 19 (76%) of the participants 9 (47%) had abnormal lung function. The most common spirometry abnormality was a restrictive pattern (forced vital capacity (FVC) < lower limit of normal (LLN)). No participant had a positive bronchodilator response. Older age was associated with a decrease in forced expiratory volume in the first second (FEV1) Z-score (−0.16, 95% confidence interval [CI] −0.31, −0.01; P = 0.04). Children on hydroxyurea similarly had reduced FEV1 Z-score (−1.5, 95%CI −2.88, −0.12; P = 0.04) and reduced FVC Z-score (−2.21, 95%CI −3.64, −0.79; P < 0.001). Conclusion: Lung function abnormalities were common among children with SCD, with restrictive abnormality predominating. Asthma and obstructive airway abnormalities were uncommon in children with SCD in South Africa.

Immune responses to P falciparum antibodies in symptomatic malaria patients with variant hemoglobin genotypes in Ghana

BackgroundHaemoglobin (Hb) variants such as sickle cell trait (SCT/HbAS) play a role in protecting against clinical malaria, but little is known about the development of immune responses against malaria parasite (Plasmodium falciparum surface protein 230 (Pfs230) and Plasmodium falciparum erythrocyte binding antigen 175 region-3 (PfEBA175-3R)) and vector (on the An. gambiae Salivary Gland Protein-6 peptide 1 (gSG6-P1)) antigens in individuals with variants Hb genotypes. This study assessed antibody (IgG) responses against malaria parasite, Pfs230 and PfEBA175-3R and vector, gSG6-P1 in febrile individuals with variant Hb genotypes.MethodsThe study was conducted on symptomatic malaria patients attending various healthcare facilities throughout Ghana. Microscopy and ELISA were used to determine the natural IgG antibody levels of gSG6-P1, PfEBA175-3R & Pfs230, and Capillarys 2 Flex Piercing was used for Hb variants determination.ResultsOf the 600 symptomatic malaria patients, 50.0% of the participants had malaria parasites by microscopy. The majority 79.0% (398/504) of the participants had Hb AA, followed by HbAS variant at 11.3% (57/504) and HbAC 6.7% (34/504). There were significantly (p < 0.0001) reduced levels of gSG6-P1 IgG in individuals with both HbAC and HbAS genotypes compared to the HbAA genotype. The levels of gSG6-P1 IgG were significantly (p < 0.0001) higher in HbAS compared to HbAC. Similarly, Pfs230 IgG and PfEBA-175-3R IgG distributions observed across the haemoglobin variants were significantly higher in HbAC relative to HbAS.ConclusionThe study has shown that haemoglobin variants significantly influence the pattern of anti-gSG6-P1, Pfs230, and PfEBA-175 IgG levels in malaria-endemic population. The HbAS genotype is suggested to confer protection against malaria infection. Reduced exposure to infection ultimately reduces the induction of antibodies targeted against P. falciparum antigens.

Distribution of ABO, RhD Blood Group among Secondary School Students at Bishops Girls Secondary School Rushere Kiruhura Southwestern Uganda

ABO and Rhesus blood group antigens are inherited genetic markers in human blood. Haemoglobin is an efficient transporter of oxygen from the lungs to the tissues and carbon dioxide from tissues to the lungs for exhalation. The study was to determine the distribution of ABO and Rhesus blood groups among secondary school female students. The blood samples of 107 secondary school students at Bishops girls’ Secondary School Rushere kiruhura Southwestern Uganda between July to August, 2023 were collected and their haemoglobin genotypes were determined using HemoTypeSC™ rapid test kit and ABO and Rhesus blood groups were determined by a standard tube method. Results. The frequencies of ABO blood groups among the study population were 20 (18.5%), 24 (22.5%), 06 (5.4%) and 57 (53.6%) for blood group A, B, AB, and O respectively. Also, the distribution of Rhesus (D) positive and Rhesus (D) negative were reported as 98 (91.6%) and 9 (8.4%) each. There was no association between ABO, Rhesus (D) and Hb genotypes observed. Data revealed that Rhesus (D) positive students were statistically higher in number compared to the Rhesus (D) negative students (p=0.000). The sequence of ABO distribution among the rural population in southwestern Uganda is; O &gt; A &gt; B &gt; AB. The frequency of Rhesus (D) negative is very low among secondary school students at Bishops’ Girls Secondary School Rushere Kiruhura Southwestern Uganda Keywords: blood groups, ABO blood group, Rh group, Haemolytic Disease of the Newborn

Steady-State Von Willebrand Factor Antigen Levels Predict Low Platelet Counts and Risk for Complications in Hospitalizations for Painful Sickle Cell Vaso-Occlusive Episodes

We previously reported that a &amp;gt;20% decline in platelet counts from steady state to presentation predicted severe complications during hospitalization for vaso-occlusive pain crisis (VOC) in 130 adult sickle cell disease (SCD) patients. 1 Sharp platelet decline in acute chest syndrome was reported to be accompanied by large von Willebrand Factor (VWF) aggregates adherent to pulmonary vascular endothelium in SCD. 2 A prospective study of 24 SCD patients found a significant increase of VWF reactivity in VOC admissions relative to steady state, which correlated with low platelet counts and the development of acute chest syndrome. 3 We aimed to investigate the role of steady-state VWF antigen level and ADAMTS13 activity as predictors of platelet count decline and severe complications in VOC admissions. Plasma levels of VWF antigen and ADAMTS13 activity were measured 4 for 56 patients at steady-state outpatient visits (Baseline). VWF antigen was expressed as fold increase or decrease from the concentration in normal pooled plasma of 12.2 ug/ml; ADAMTS13 activity was expressed as fold of the value from normal pooled plasma which was considered 100% activity. Electronic records of VOC admission that occurred &amp;gt;21 days after Baseline were reviewed. Exclusion criteria included non-VOC admissions defined as elective admission for surgery, admission for accident or injury, admission for delivery of an infant, or admission with a pain score &amp;lt;8/10 at presentation. 5 A total of 98 qualifying admissions were identified. Severe complication during the admission was defined as having any of the following: 1) acute chest syndrome, new infiltrate on chest X-ray, or use of ventilator; 2) acute kidney injury; 6 3) acute liver injury; 7 4) thrombotic or hemorrhagic stroke; 5) venous thromboembolism including deep vein thrombosis, atrial thrombosis, and pulmonary embolism; 6) need for transfer to the intensive care unit; 7) need for exchange blood transfusion; 8) death during hospitalization. Platelet counts at presentation to the emergency room (ER) leading to the admissions under study were recorded, as well platelet counts at Baseline. The 56 patients had a median (range) age of 37 (21-66) years; 52% are female, 89% with hemoglobin SS or Sβ 0-thalassemia, and 57% on hydroxyrea (HU). Severe complication occurred in 35 (36%) of the 98 admissions involving 27 (48%) of the patients. Focusing on the first admissions, higher steady-state VWF antigen levels correlated strongly with lower ER platelet counts (ρ= -0.50, P=0.00011, Figure 1A) and higher steady-state ADAMTS13 activity correlated weakly with ER platelet counts (Spearman's ρ= 0.30, P=0.025). The ratio of VWF antigen to ADAMTS13 activity ratio also correlated strongly with lower ER platelet counts (ρ= -0.52, P=0.000052, Figure 1B). In contrast, steady-state VWF antigen level (ρ= -0.17, P=0.23), ADAMTS13 activity (ρ= 0.19, P=0.17), and VWF antigen to ADAMTS13 activity ratio (ρ= -0.23, P=0.098) showed no significant correlation with steady-state platelet counts. The correlations remained by adjusting for age, gender, Hb genotype severity, HU, and treatment of anticoagulant, aspirin, or non-steroidal anti-inflammatory drugs at VOC visits. In analyses restricted to admissions &amp;gt;1 year after Baseline, the correlation between steady-state VWF antigen level and ER platelet counts appeared to persist. Focusing on the 28 first admissions, steady-state VWF antigen level (ρ= -0.50, P=0.0071) and VWF antigen to ADAMTS13 activity ratio (ρ= -0.44, P=0.018) correlated negatively with ER platelet counts. Steady-state ADAMTS13 activity did not correlate with ER platelet counts in admissions that occurred &amp;gt;1 year after Baseline (ρ= 0.16, P=0.43). We further examined the association of steady-state VWF antigen level, ADAMTS13 activity, and their ratio with risk for severe complication in admission. Focusing on the first 56 admissions, which involved 23 complications, steady-state VWF antigen level in the top quartile (1.63) associated with risk for severe complications (OR=6.5, 95% CI 1.4-31, P=0.018, n=56), adjusting for age, gender, Hb genotype severity, and HU. Our observations suggest that steady-state VWF antigen level and the ratio of VWF antigen level to ADAMTS13 activity predict low platelet counts at presentation to VOC admissions, and that steady-state VWF antigen level in SCD patients may be a relatively stable marker for risk of severe VOC complications.

Donor Hemoglobin Genotype Does Not Impact Outcomes Following Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Study

Sickle cell disease (SCD) is an inherited hemoglobin (Hb) disorder which leads to significant morbidity and early mortality. Hematopoietic cell transplantation (HCT) is the only curative treatment with long-term outcome data, demonstrating excellent symptom-free survival particularly when a matched related donor (MRD) is available. Most MRD have sickle cell trait (Hb AS), but trait donor HCT is considered acceptable by the FDA and without negative impact. Further, initial gene addition and editing approaches for SCD have resulted in a trait-like status with benefit. Sickle trait, however, is associated with complications such as papillary necrosis, bacteriuria, splenic infarction, and exercise-induced death. The primary aim of this study was to compare long-term outcomes following MRD HCT for SCD based on donor Hb genotype, to objectively describe any impact on outcomes. Retrospective data was available for this analysis on 182 SCD patients ≥1 year post MRD HCT at 10 participating Sickle Transplant Advocacy and Research (STAR) Alliance centers. Summary statistics were presented as mean (standard deviation) for continuous variables and count (%) for categorical variables. Comparisons were made between Hb AA and Hb AS donor groups using both parametric and non-parametric tests for continuous variables and Chi-square test/exact test for categorical variables, with p-value &amp;lt;0.05 set as significant. Amongst 182 patients undergoing MRD HCT, 67% (n=122) had a Hb AS donor ( Table). In the overall cohort, median age at HCT was 8.7 (4.8) years and most patients had HbSS (n=174; 96%) with a severe clinical phenotype (n=97; 54%). HCT was performed using bone marrow (n=166; 92%) with myeloablative conditioning (n=156; 86%) in the majority. Patients with a severe disease phenotype and Hb AS donor were significantly more likely to have recurrent vaso-occlusive pain crises as an indication for HCT (p=0.033), otherwise there were no differences in baseline patient or HCT characteristics between cohorts. With mean post-HCT follow up of 4.5 (3.9) and 5.1 (4.1) years in Hb AA and Hb AS donor cohorts (p=0.145), no significant differences were seen in recipient outcomes including time to neutrophil and platelet engraftment, number of or time to last platelet transfusion, myeloid or unsorted % donor chimerism, number with acute (day 100) or chronic GVHD (1 year), or time to discontinue immunosuppression (data not shown). Disease recurrence and need for 2 nd HCT were rare in both cohorts (AA: 2 [3%] and 2 [3%]; AS: 3 [3%] and 4 [3%]; p=0.665 and 1.0, respectively). Two (3%) and 5 (4%) patients died in the AA and AS cohorts, respectively (p=1.0). Aside from a statistically (but not clinically) significant difference in Hb at day 30 (p=0.044), no difference was seen in longitudinal Hb or markers of hemolysis (LDH and ARC; Figure). No significant difference was seen in median number of RBC units transfused (AA: 4.0 [2.0-6.0]; AS: 3.0 [2.0-6.0]; p=0.454) or days to last transfusion (AA: 23.0 [14.0-77.0]; AS: 22.0 [13.0-75.0]; p=0.86). SCD complications were rare post-HCT, with no difference seen between cohorts in number (%) with VOC (AA: 1 [2%; had 2 separate VOC events]; AS: 3 [3%]; p=1.0), ACS (none reported), chronic pain (AA: 0 [0%]; AS: 1 [&amp;lt;1%]; p=1.0), or other SCD-related complications (AA: 2 [3%]; AS: 9 [7%; had 11 separate other events]; p=0.456). Stroke occurred in a significantly higher proportion with an AA versus AS donor (5 [8%] and 2 [2%], respectively; p=0.04). No significant differences were seen in longitudinal (1 and 2 years and at last follow up) post-HCT cardiac (EF, SF, TRJ velocity), pulmonary (FEV1, FVC, DLCO), or renal (GFR) function between cohorts (data not shown). Our results indicate that in MRD HCT for SCD, AS and AA donors yield comparable long-term outcomes. In this retrospective and registry-based study design, detailed analyses did not show differences between the two cohorts at baseline or at any timepoint post-HCT. While there were some outcome differences between the cohorts, they were either not clinically significant or did not have a scientific rationale, and thus were likely due to chance alone (denoted by bolding in Table). Given the young age of our cohort at HCT and thus a smaller proportion with SCD-related organ dysfunction, our results may not be applicable to an older cohort with significant organ dysfunction which will require a separate analysis.

Demographics and outcomes of hemoglobin genotype in hospitalized patients with COVID-19 and sickle cell disease in the United States.

Coronavirus disease 2019 (COVID-19) is associated with poor outcomes in sickle cell disease (SCD) patients. However, there is a paucity of data comparing hemoglobin (Hb) genotypes in SCD and infection outcomes. The National Inpatient Sample was used to identify the record of hospitalizations with COVID-19 and SCD in 2020 using the International Classification of Disease, Tenth Revision codes. Study outcomes (invasive mechanical ventilation, extracorporeal membrane oxygenation, shock, vasopressor use, measures of resource utilization, and in-hospital mortality) were compared between hemoglobin SS, SC, and S-beta thalassemia (Sβ). Of the 102 975 COVID-19 hospitalizations with SCD, 87.26% had HbSS, 7.16% had HbSC, and 5.58% had HbSβ. Younger patients were more likely to have HbSS, while older patients were likely to have HbSC and HbSβ. HbSS was more frequent with Blacks, while HbSβ was more prevalent with Whites and Hispanics. Though measures of resource utilization were higher in HbSS, there was no significant difference in in-hospital outcomes between the three genotypes. There is no difference in COVID-19 outcomes among Hb genotypes in SCD. Further studies are needed to explore the reasons for this observation.

Incidence and risk factors for osteonecrosis of the femoral head in five hundred and ten sickle cell disease paediatric patients.

Osteonecrosis of the femoral head (ONFH) is a degenerative and progressive disorder that mainly affects people with sickle cell disease (SCD). Herein, we aimed to search for a better understanding of markers that can act as risk factors for ONFH in patients with SCD. We conducted a retrospective study including 510 SCD patients followed over 23years. Patients were divided into the ONFH group and the no-ONHF control group. Univariate and multivariate logistic regression analyses were performed to identify risk factors. Among 510 SCD patients, 41(8%) were diagnosed with ONFH at a mean age of 167months ± 64 (72-288). The cumulative incidence of ONHF increased from 2.3% at tenyears to 18.3% at 20years of age. The radiological grade 3 ONHF was predominant. No significant differences in sex, age at diagnosis of SCD, and Hb genotype were found between groups. The patient age and the time since diagnosis of SCD were statistically higher in patients with ONHF in univariate and multivariate analysis. ONHF was also associated with higher creatinine level (p = 0.001) lower LDH level (p = 0.006), and higher number of vaso-occlusive crisis (VOC)/patient/year (p < 0.001). The cumulative incidence of ONHF in patients having more than 3 VOC/year was significantly higher (43% versus 18.9% at 20years, p < 0.001). In addition, infections, gallstones, growth delay, delayed initiation of hydroxyurea, and a higher transfusion rate were significantly associated with ONFH. These findings confirm that ONFH is closely related to the age, severity, and duration of SCD. Better management of this disease prevents acute and chronic complications, and early screening of the ONFH as soon as the first signs of the severity of the disease are detected provides a better functional prognosis.

Detection and prevalence of HBsAg and HBV DNA among visiting patients attending health facilities in Nigeria

Hyper-endemicity of the Hepatitis B virus (HBV) has for long been retained in parts of Sub-Saharan Africa, including Nigeria with a prevalence rate above 8%. Despite the implementation of vaccination programs, factors such as inadequate diagnostic protocols, the prevalence of occult infections, and population group-specific susceptibility to infection remain overlooked in control strategies. This study, therefore, aims at investigating the prevalence of hepatitis B viral infection, the presence of mutant strains, and establishing a link between age, blood parameters and susceptibility to infection. A total of 451 blood samples from participants aged 1–50 years were tested for the presence of hepatitis B surface antigen (HBsAg) and HBV DNA using rapid diagnostic testing and PCR molecular-based assay. Age, blood group and hemoglobin (Hb) genotype were used to evaluate associated risk of infection. Statistical analysis was done using Python3. A prevalence of 5.8% and 18.2% were recorded using rapid diagnostic testing and PCR molecular-based assay respectively. Correlation between age and, HBV DNA and HBsAg positivity gave a p-value of 1.672. Error rates of 4.4% and 16.9% were recorded for false positives and false negatives respectively, with a rapid test kit sensitivity of 7.32% and specificity of 94.58%. Blood group O rhesus D positive (O⁺) showed a statistically significant higher risk of infection (P < 0.001, odd ratio (OR) = 0.38, 95% CI = 0.23–0.63) compared to non-O blood types. Age groups 21- 30 years and 31–40 years, both showed high relative risk and odd ratios. The low sensitivity found for the available RDT kits negatively influenced the ability to screen for Hepatitis B strains, hence, the high rate of false negatives. The Hb genotype may also play some role or have some association with the viral infection. This study highlights areas to specifically look into in implementing HBV eradication strategies.

Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels.

Malaria affects a significant portion of the global population, with 247 million cases in 2021, primarily in Africa. However, certain hemoglobinopathies, such as sickle cell trait (SCT), have been linked to lower mortality rates in malaria patients. Hemoglobin (Hb) mutations, including HbS and HbC, can cause sickle cell disease (SCD) when both alleles are inherited (HbSS and HbSC). In SCT, one allele is inherited and paired with a normal allele (HbAS, HbAC). The high prevalence of these alleles in Africa may be attributed to their protective effect against malaria. Biomarkers are crucial for SCD and malaria diagnosis and prognosis. Studies indicate that miRNAs, specifically miR-451a and let-7i-5p, are differentially expressed in HbSS and HbAS compared to controls. Our research examined the levels of exosomal miR-451a and let-7i-5p in red blood cells (RBCs) and infected red blood cells (iRBCs) from multiple sickle Hb genotypes and their impact on parasite growth. We assessed exosomal miR-451a and let-7i-5p levels in vitro in RBC and iRBC supernatants. Exosomal miRNAs exhibited distinct expression patterns in iRBCs from individuals with different sickle Hb genotypes. Additionally, we discovered a correlation between let-7i-5p levels and trophozoite count. Exosomal miR-451a and let-7i-5p could modulate SCD and malaria severity and serve as potential biomarkers for malaria vaccines and therapies.

5613191 KNOWLEDGE, ATTITUDE, PRACTICE OF GENOTYPE SCREENING AMONG UNDERGRADUATES MEDICAL STUDENTS IN THE UNIVERSITY OF ABUJA

Background: Sickle cell disease remains the most common life threatening genetic disorder worldwide. Globally about 312,000 children are born each year with sickle cell disease (SCD), half of which are from Nigeria1,2,4,5,7,8. The prevalence of sickle cell anaemia (SS) in Nigeria is estimated to be 20 per 1000 and 25% of the population have sickle trait (AS)2,6,9,10,11. Medical students in Nigeria are key in the future management of sickle cell disease. Therefore, it is important to understand what training in SCD is given to medical students in Nigeria and to identify any important knowledge gaps which may improve training curricula. Method: A student survey was conducted at the College of Health Sciences, University of Abuja in the Federal Capital Territory of Nigeria (FCT) in the 2021/2022 academic year. At this University, all students undergo comprehensive medical tests before admission, which include genotype screening. All medical students were eligible to complete the survey and which was advertised through year group social platforms. Data were collected using a self-administered questionnaire through Google form, after the respondent indicated their consent. The questions focused on knowledge of the disease and attitude towards genotype screening, and whether the student had undergone screening and were aware of their status. Results: In the academic year of 2021/2022 there were a total number of 374 medical students from year one to year six of these 150 (40%) completed the survey. Survey respondents included similar numbers of males and females, with a mean age of 23.7 years and were from all years of study. All the respondents had heard about sickle cell disease and 85% stated that they had attended courses which covered Sickle cell disease topics (from 63% in 1st year of study rising to over 90% by year 3). A very high proportion knew that Sickle cell disease trait can be transmitted from both parents to offspring (95%), and 90% knew that SCD can affect anyone and can occur when both parents are carriers of the Sickle gene. Fewer students (79%) knew that SCD can be diagnosed at birth. Knowledge of common symptoms for sickle cell patients was variable, while most knew that one of the most common complaints was pain in the limbs (92%), only 23% were aware that yellow eyes is also a common symptom, and 10 students (7%) incorrectly identified skin rashes as a common symptom. A total of 93% of students had been genotype-screened for SCD, and attitudes towards genotype screening, was generally positive. Most agreed that genotype screening can help prevent SCD and that pre-conception genotype screening is important. Of those who had been screened and knew their status, 68.6% were AA (adult haemoglobin without any haemoglobin disorder), 28.6% were AS (had the sickle cell trait) and 2.9% were SS (sickle cell anaemia). Conclusion: Over 90% respondents knew their sickle cell status (Hb genotype) and 2.9% had SCD (HbSS), and 29% had sickle cell trait (HbAS) consistent with the national burden in Nigeria. Reassuringly, medical students had a good knowledge of and attitude towards SCD irrespective of their year of study. Although identifying symptoms, which may be important in diagnosis, could be improved. Given that almost half of the global burden of SCD is in Nigeria, this study reflects the importance of ensuring adequate health education towards sickle cell disease among Nigerian medical students.

A review of outcomes of laser photocoagulation for Goldberg stage 3 proliferative sickle cell retinopathy

Topic: A review of outcomes of laser photocoagulation for Goldberg stage 3 proliferative sickle cell retinopathy (PSR) in a Eye Foundation Hospital. Aims and objectives: To report regression of retina neovascularization and visual outcomes after prophylactic scatter retina laser photocoagulation for Goldberg stage 3 PSR in a tertiary private hospital in sub-Saharan Africa. Methods: A retrospective review of case files of patients who were treated with prophylactic scatter retina laser photocoagulation between January 2017 and June 2022 following a diagnosis of PSR in a Eye Foundation Hospital, Ikeja, Lagos, Nigeria, was done. Results: A total of 124 eyes of 62 patients with PSR were seen within the period under consideration. A majority of patients (49 (79.0%)) had hemoglobin (Hb) genotype SC, while 13 patients (21%) were Hb genotype SS. At presentation, 29 eyes (23.3%) had Goldberg stage 2 PSR, 55 eyes (44.4%) had Goldberg stage 3 PSR, 27 eyes (21.8%) had stage 4 PSR, while 13 eyes (10.5%) had stage 5 PSR. All 55 eyes (49.2%) with stage 3 PSR were treated with prophylactic retina laser photocoagulation. At the patients’ last clinic visit, 34 eyes (61.8%) had the same visual acuity (VA) as at presentation, 11 eyes (20%) had improvements in VA, while 10 eyes (18.2%) had worse VA. Laser treatment success (regression of seafan neovascularization) was seen in 50 eyes (90.9%), while five eyes (8.1%) had unsuccessful laser treatment. Conclusion: A high percentage (90.9%) of resolution of retina neovascularization secondary to PSR at stage 3 of Goldberg’s classification was seen after prophylactic scatter retina laser photocoagulation in our group of evaluated patients. Most patients (81.8%) maintained or had improvements in their visual acuities over the period of follow-up. More clinical research is required to further evaluate outcomes of laser photocoagulation for PSR.

Pattern of Hb genotype in surgical patients at a tertiary hospital in Southern, Nigeria

Background: Haemoglobin (Hb) genotype is not a routine test in adult pre-operative investigations in majority of clinical settings, though in the obstetric and gynaecological patients already have their Hb genotype as a part of the routine antenatal investigations. However, in paediatric work up for surgical procedures Hb genotype is a routine investigation. This is due to sickle cell endemicity in our locality. Aim: To determine the pattern of HB Genotype in surgical patients at the Rivers State University Teaching Hospital (RSUTH). Method: This was a one-year retrospective study of surgical patients (Surgery and Obstetrics/Gynaecology departments) of the RSUTH. The patients comprised of all the consecutive cases of the surgeries in these departments for the period under review. Ethical clearance was obtained from ethical committee of the Rivers State Hospital Management Board. Structured profoma was used to extract information from patients’ case notes and analyzed using SPSS version 25. Result: There were a total of 370 subjects that were recruited for the study under review. There were 146 (39.5%) males and 224 (60.5%) females. The mean age was 31 years. The age range was 22 years to 56 years. One hundred and ninety four (52.4%) were obstetrics and gynaecological surgeries while 176 (47.6 %) were non-gynaecological surgeries. The commonest indication for surgery was caesarean representing 126 (34.1%) of the subject. The most common Hb genotype was AA 246 (66.5%)of which females contributed to 148 (40%) and males 98(26.5%)had Hb AA while 124 (33.5%)of the subjects were Hb AS. Females that were Hb As were 74 (20%) while males were 50 (13.5%). There were no subjects that were Hb SS. Conclusion: This study showed the most prevalent Hb Genotype as AA (66.5%) in surgical patients at the Rivers State University Teaching Hospital (RSUTH), while 33.5% had Hb AS genotype. None of these subjects had sickle cell (HbSS) homozygous trait

MiR-451a and let-7i-5p loaded extracellular vesicles attenuate heme-induced inflammation in hiPSC-derived endothelial cells.

Hemolysis is associated with many pathologies, including trauma, sepsis, hemorrhagic stroke, malaria, and genetic disorders such as sickle cell disease (SCD). When hemolysis occurs, free-heme drives vascular inflammation, resulting in oxidative tissue damage and cardiometabolic complications. A better understanding of heme clearance and detoxification is essential to preventing sustained tissue damage. Human induced pluripotent stem cell (hiPSC)-derived endothelial cells (hiPSC-ECs) provide a novel source of patient-specific cells and tissues for disease modeling, drug discovery, and regenerative therapeutics. Here we report the use of hiPSC-ECs to elucidate the role of miR-451a and let-7i-5p-loaded extracellular vesicles (EVs, such as exosomes) in the inflammatory response to free-heme as a model for heme-induced inflammation. We provide evidence of a significant correlation between miR-451a and let-7i-5p-loaded circulating exosomes in plasmodium-infected patients with reported clinical benchmarks of malaria-severity (e.g., Hemoglobin (Hb) levels, white blood cell counts). Additionally, we determined that exposure of Plasmodium falciparum (Pf) parasites to EVs, loaded with either miRNA, significantly reduces their counts in vitro. Using hiPSCs derived from individuals with wild-type Hb (HbAA) or homozygous sickle cell mutated Hb (HbSS) genotypes, we demonstrate that heme-treated hiPSC-ECs secreted inflammatory products (cytokines, chemokines and growth factors) into supporting media at concentrations that were similar to that reported in HbAA and HbSS serum. This inflammatory response was attenuated by exposure with miR-451a or let-7i-5p-loaded EVs. We also found a decrease in transcription of ICAM1 and P-Selectin, as well as the secretion of key inflammatory cytokines (e.g., CXCL10, TNF-α, and IFN-γ). Based on these findings, we propose a model in which increased levels of exosomal miR-451a and let-7i-5p in Plasmodium-infected individuals will attenuate inflammatory responses to free-heme and parasite-derived products. As a result, infected erythrocytes will less likely adhere to the endothelium, sequester in brain micro vessels, and reduce vaso-occlusive crises that exacerbate cerebral malaria.

Risk factors for Venous Thromboembolism and clinical outcomes in adults with sickle cell disease

IntroductionThe natural history of venous thromboembolism (VTE) in sickle cell disease (SCD) is incompletely understood. We hypothesized that VTE recurrence is common in SCD and associated with increased disease severity. We sought to understand the short- and long-term clinical outcomes of VTE in SCD. MethodsWe conducted a single-center retrospective chart review study of patients with SCD 18 years and older at our institution between 2003 and 2018. Demographics, hemoglobin (Hb) genotype, medical history, and laboratory values were collected. We recorded VTE occurrence and potential provoking factors, duration of anti-coagulation and subsequent recurrence of VTE. We compared rates of emergency department (ED) visits, and hospitalizations for five years post-VTE to rates of ED visits and hospitalizations among those without VTE. ResultsFifty-five (23.6%) of 233 individuals with SCD in our cohort (69% HbSS/HbS-β0) had a VTE. Increased BMI, prior splenectomy, and white blood cell count were significantly associated with increased risk of VTE while Hb genotype, and severity of anemia were not. Recurrent VTE occurred in 27/55 (49%); 13 VTE recurrences occurred during active treatment with anticoagulants. Patients with a VTE had significantly higher rates of ED visits and hospital admissions than those without a VTE. ConclusionNearly a quarter of our single institution cohort had a VTE with a high recurrence rate even in those receiving anti-coagulation therapy. SCD patients had a higher rate of healthcare utilization after a VTE suggesting a link to disease severity.

Genetic variation in haemoglobin is associated with evolved changes in breathing in high-altitude deer mice

Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated whether genetic variants in haemoglobin (Hb) that contribute to high-altitude adaptation in deer mice (Peromyscus maniculatus) are associated with evolved changes in the control of breathing. We created F2 inter-population hybrids of highland and lowland deer mice to test for phenotypic associations of α- and β-globin variants on a mixed genetic background. Hb genotype had expected effects on Hb-O2 affinity that were associated with differences in arterial O2 saturation in hypoxia. However, high-altitude genotypes were also associated with breathing phenotypes that should contribute to enhancing O2 uptake in hypoxia. Mice with highland α-globin exhibited a more effective breathing pattern, with highland homozygotes breathing deeper but less frequently across a range of inspired O2, and this difference was comparable to the evolved changes in breathing pattern in deer mouse populations native to high altitude. The ventilatory response to hypoxia was augmented in mice that were homozygous for highland β-globin. The association of globin variants with variation in breathing phenotypes could not be recapitulated by acute manipulation of Hb-O2 affinity, because treatment with efaproxiral (a synthetic drug that acutely reduces Hb-O2 affinity) had no effect on breathing in normoxia or hypoxia. Therefore, adaptive variation in Hb may have unexpected effects on physiology in addition to the canonical function of this protein in circulatory O2 transport.

Haemoglobin (Hb) Genotype Profile in COVID-19 Disease Susceptibility and Severity in Lagos State Nigeria

COVID‐19 pandemic has posed unique challenges to the health providers involved with chronic diseases like Haemoglobin disorders (sickle cell disease). Therefore, this study highlights the susceptibility and severity of COVID‐19 associated with normal and haemoglobin variants. This study is a case series that includes patients evaluated between June and August 30, 2020, and diagnosed with COVID-19 by the Quantitative Polymerase Chain Reaction method. Alkaline haemoglobin electrophoresis was used to identify types of Haemoglobin genotype associated with mild-to-severe cases of COVID-19. A total of 697 COVID-19 patients were included in this study, with a mean age of 41.32 (12.917). There were more males (66.1%) than females. The most frequently detected genotype was AA (75.8%), followed by AS (22%). Severe conditions of COVID-19 were present in patients with HBAC 2(14.28%) and HBAS 13 (8.5%). Co-morbidities were present in (24.0%) of the patients, with a mortality rate of 1.3%. Patients with pneumonia in association with other co-morbidities are 26 times more likely to have severe SARS CoV-2 than those with only pneumonia, irrespective of their haemoglobin genotype profile. The clinical course is seen in normal haemoglobin, and the variant with COVID-19 was the same. It is suggested that people with haemoglobin variant are not at increased risk during COVID-19 infection or risk of a sickle cell crisis.

The prevalence of sickling abnormality in Oman: A review of relevant publications

Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. The prevalence of sickle cell trait and disease reaches up to 4.8–6% and 0.2% respectively, which is the highest among the Arab Gulf states. Omani population represents a variability of HbS genotype combinations with other Hb genotypes modify the clinical severity of the disease. The most prevalent sickling abnormality in Oman is Hb S/S (SCA) followed by Hb S/β-thalassemia. Omani children with SCD with high Hb F level had less severe disease. More than two-thirds of SCD cases were running a mild course of the disease due to the high prevalence of α-thalassemia trait. The severity index has been correlated with the early age of presentation, the absence of α-thalassemia trait and the lower level of HbF as well as to the existence of different β-globin gene haplotypes. S/ β0 presented with the same clinical severity of S/S while those with S/ β+ had some splenic function into adulthood and were more prone to splenic sequestration. The unique existence of HbS-Oman (a severe variant of sickle hemoglobinopathy) markedly increased the severity of the disease. Compound heterozygotes HbS-Oman resulted in very severe clinical manifestations with transfusion-dependency and hypersplenism early in life. This paper summarizes and reviews βs gene haplotypes in patients with sickle cell anemia (SCA) in Oman. (www.actabiomedica.it)

Prevalence of Plasmodium Falciparum among Medical Students with different ABO Groups and Electrophoretic Patterns in a Tertiary Institution in Nnewi, Nigeria

There is evidence that Plasmodium falciparum (Pf) malaria is influenced by ABO blood type but the extent of association is not fully established. Some investigators opinioned that haemoglobin electrophoretic patterns are a factor in susceptibility to Pf infection but there is no consensus on possible association between it and ABO blood group and Hb genotypes. This study was designed to determine the prevalence of Pf among different ABO blood groups and Hb electrophoretic patterns of medical students of a tertiary institution in Nnewi, Nigeria. A total of 80 subjects (41 males and 39 females) aged 18-30 years who reported to the Medical Centre of the institution on account of febrile illness were recruited for the study. Information on age, previous malaria episodes and recent use of prophylaxis were sought. Three milliliters (3ml) of blood were collected into EDTA container for ABO grouping, Hb electrophoresis and blood films for P. falciparum detection and quantification by microscopy. Pf prevalence among the subjects was 47.5% (38/80). Thirty-one (38.75%) of the subjects were of blood group O, 27 (33.75%) group A, 19 (23.75%) blood group B and 3(3.75%) blood group AB. Fifty-two (65%) of the subjects were Hb AA and 28 (35%) AS. No significance difference was seen between malaria episodes and ABO blood groups; Hb electrophoretic patterns; gender and parasite density (p&gt;0.05) respectively. A negative correlation was observed between parasite density and age (r= -0.180, p = 0.109). Pf infection, frequency of infection and parasite load is not influenced by blood group and Hb electrophoretic patterns in our study population.

Analysis of clinical presentation, hematological factors, self-reported bed net usage, and malaria burden in sickle cell disease patients.

BackgroundSickle cell anemia (SCA) is a severe monogenic disorder, caused by single nucleotide mutations in the hemoglobin (Hb) gene, that is prevalent in malaria endemic regions of the world. Sickle cell trait (SCT) individuals carry only one of the mutated alleles and were shown to be protected against malaria. However, defining the relative contribution of hematological, clinical, and environmental factors to the overall burden of malaria in individuals with hemoglobinopathies such as SCA has been challenging.MethodsWe hypothesized that hematological differences, clinical presentations, and self-reported bed net usage among Plasmodium-infected and uninfected individuals may govern overall malaria burden in individuals with sickle cell disease (SCD). We conducted a cross-sectional study in Ghana from 2014 to 2019 and described clinical presentations, hematological characteristics, and bed net use based on a comprehensive questionnaire. Hematological characteristics were compared using a parametric or nonparametric ANOVA, pending if data passed D'Agostino & Pearson normality test. When comparing only two Hb genotypes hematological characteristics a Mann–Whitney U-test were used. Logistic regressions and Chi-squared tests were used to compare questionnaire responses between Hb genotypes. All statistical significance was set at p < 0.05.FindingsMultiple hematological parameters were significantly (p < 0.05) altered depending on sickle cell genotype and/or malaria status. When compared to other Hb genotypes, SCA individuals with or without malaria had significantly (p < 0.05) higher WBC and platelets counts and lower Hb levels. While the sickle cell genotype may affect malaria severity, SCT and SCA participants were found to significantly (p < 0.007) use bet nets more than HbAA participants.InterpretationsOur findings can be utilized to enhance national guidelines for reducing the incidence of malaria especially among individuals with SCD, SCT protection and health disparities among hemoglobinopathies.FundingThis study was supported by the National Institute for Health.

Transcranial Doppler Findings Among Gulf Arabs

▪Background: Transcranial Doppler (TCD) is used to identify patients with sickle cell disease (SCD) at risk for stroke. We have carried out TCD studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Southern Iraq and UAE) to document the prevalence of abnormal TCD findings.Methodology: The patients were recruited from outpatient clinics and studied in steady state. TCD was performed using standard equipment with experienced operators. Time-averaged mean of maximum velocity (TAMMV) was documented in the arteries of the Circle of Willis. The hemoglobin (Hb) genotype was confirmed and the fetal Hb (HbF) level and complete blood counts were determined.Results: There were 415 patients in the study, aged 2 to 18 years (mean of 8.6±3.5). None of the patients had abnormal TAMMV (i.e. >200 cm/sec), while only 13 (3.1%), all from Iraq had conditional values in the right middle cerebral artery (MCA) and 7 (1.7%) in the left MCA. There were no significant gender differences, and both the Hb genotype (SS, Sβ0thal or SD) and the use of hydroxyurea did not show consistent influence on TAMMV. Total hemoglobin, reticulocyte count, serum bilirubin and HbF showed varying degrees of association with TAMMV in the different vessels.Conclusions: This study has demonstrated the rarity of abnormal TCD findings among Peninsular Arab patients with SCD. This might be related to the haplotype, elevated HbF or may represent a racial variation. The guidelines for TCD screening in this population need further studies and recommendations. DisclosuresNo relevant conflicts of interest to declare.