Ferroptosis as an emerging target in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.

Evaluation of the Newborn Screening Pilot for Sickle Cell Disease in Suriname Using the Non-Adoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) Framework.

The early detection of sickle cell disease (SCD) is vital to reduce mortality among affected children. Suriname currently lacks a newborn screening programme (NSP) for SCD. We performed a pilot programme to evaluate the scalability of such an initiative. Dried blood spots were collected from five birth centres and subjected to electrophoresis analysis. The programme scalability was evaluated using the non-adoption, abandonment, scale-up, spread, and sustainability framework. Challenges across six domains (illness, technology, value proposition, adopter system, organisation, and societal system), were categorised hierarchically as simple 😊, complicated 😐, or complex 😢. It has been proven that implementing programmes with mainly complicated challenges is difficult and those in mainly complex areas may be unachievable. SCD was detected in 33 of 5185 (0.64%) successfully screened newborns. Most of the domains were classified as simple or complicated. Disease detection and technology suitability for screening in Suriname were confirmed, with favourable parental acceptance. Only minor routine adjustment was required from the medical staff for programme implementation. Complex challenges included a reliance on external suppliers for technical maintenance, ensuring timely access to specialised paediatric care for affected newborns, and securing sustainable financial funding. Scaling up is challenging but feasible, particularly with a targeted focus on identified complex challenges.

Exploring the role of viscosity-vaso-occlusion and haemolysis-endothelial dysfunction in pain sensitization among Jamaicans with sickle cell disease.

Viscosity-vaso-occlusion (VVO) and haemolysis-endothelial dysfunction (HED) are pathophysiological mechanisms and clinical subphenotypes of sickle cell disease (SCD). Recurrent vaso-occlusive crises (VOC) may lead to neuroplastic changes and pain sensitization. Among 257 SCD participants, we assessed the relationship of subphenotypes with pain sensitivity using quantitative sensory testing to identify heat pain thresholds (HPT) and pressure pain thresholds (PPT). VOC history and sleep, social and emotional functioning were assessed using the adult sickle cell quality of life measurement information system. The 'elbow method' determined the optimal number of clusters as three. Clustering was performed using K-prototypes. Among clusters 2 and 3, VOC frequency and severity were higher. Clusters 1 and 3 had lower haemoglobin, higher reticulocytes and lactate dehydrogenase and more leg ulcers. In multivariate regression, cluster 3 was associated with approximately 13.6% lower PPT compared to cluster 1, and female sex was associated with decreases in PPT and HPT at the hands and feet (p < 0.001). Hydroxyurea use and unit increases in sleep functioning and age were associated with approximately 20.1% higher foot-PPT, 6.8% higher hand-PPT and 2.5% higher hand-HPT and foot-HPT respectively. Findings suggest that a third subphenotype with mixed VVO and HED features and worse pain sensitization may exist.

Highly Defined Induced Pluripotent Stem Cell Lines Mimic Donor Red Blood Cell Antigen Profiles for Therapeutic and Diagnostic Use.

Our group generated two induced pluripotent stem cell (iPSC) lines for in vitro red blood cell (RBC) production from blood donors with extensively known erythrocyte antigen profiles. One line was intended to give rise to RBCs for transfusions in patients with sickle cell disease (SCD), while the other was developed to create RBC panel reagents. Two blood donors were selected based on their RBC phenotypes, further complemented by high-throughput DNA array analysis to obtain a more comprehensive erythrocyte antigen profile. Enriched erythroblast populations from the donors' peripheral blood mononuclear cells were reprogrammed into iPSCs using nonintegrative plasmid vectors. The iPSC lines were characterized and subsequently subjected to hematopoietic differentiation. iPSC PB02 and iPSC PB12 demonstrated in vitro and in vivo iPSC features and retained the genotype of each blood donor's RBC antigen profile. Colony-forming cell assays confirmed that iPSC PB02 and iPSC PB12 generated hematopoietic progenitors. These two iPSC lines were generated with defined erythrocyte antigen profiles, self-renewal capacity, and hematopoietic differentiation potential. With improvements in hematopoietic differentiation, these cells could potentially be more efficiently differentiated into RBCs in the future. They could serve as a complementary approach for obtaining donor-independent RBCs and addressing specific demands for blood transfusions.

[Sickle cell disease in French Guiana: assessing 30 years of neonatal screening (1992-2021)]. / La drépanocytose en Guyane : bilan de 30 années de dépistage néonatal (1992-2021).

Background: Sickle cell disease is one of the most common genetic diseases in France. In French Guiana, neonatal screening was introduced in 1992, at the same time as other screening programs for childhood diseases. The aim of this study is to describe the organization of newborn screening for sickle cell disease in French Guiana. Materials and methods: We used several data sources: data collected from hospital records since 2005, activity reports from the national neonatal screening program and data from screening campaigns organized by the Drepaguyane association between 2010 and 2021 on 1,300 subjects. Blood samples from newborns are collected by capillary or venous sampling and absorbed on blotting paper (Guthrie) at the same time as those for other neonatal screenings. The dried papers are sent to the inter-regional laboratory in Lille, for further processing. In Saint-Laurent-du-Maroni, in order to reduce the proportion of people lost to follow-up, a double screening is carried out and the results are returned before discharge from the maternity hospital. All data were entered into an anonymous Excel file. The data were analyzed using STATA software. Results: Among the 175,593 screened neonates between 1992 and 2021, screening detected 823 infants with sickle cell disease and 17,950 heterozygotes. Sickle cell genotypes include 493 SS (60%), 302 SC (37%) and 28 S-Beta-thalassemia (3%). The incidence of sickle cell disease was 1/213, 95% CI [1/236-1/204], and that of heterozygotes 1/10, IC 95% [1/12-1/8]. The majority of these children (52%) were from the Maroni region. The delay between screening and test results was 7 days. Only pathological results (homozygous, heterozygous) were communicated to parents and/or the attending physician by post. These data confirm the upward trend in the number of children screened for sickle cell disease in French Guiana. Data from screening campaigns organized by the Drepaguyane association have enabled to describe the distribution of the various abnormal hemoglobin fractions, and to confirm that HbS is more frequent in Western French Guiana. In Cayenne, in 2021, the active file comprised 699 patients, including 266 children under 18 years old. Discussion and conclusion: This study provides valuable data on 30 years of neonatal screening for sickle cell disease in French Guiana, and on the evolution of sickle cell disease patients. It confirms that French Guiana is the French territory with the highest incidence of sickle cell disease. This incidence continues to rise over time. The study reveals the improvement in the organization of sickle cell disease management in French Guiana between 1992, when screening was introduced, and the present day. It highlights the role of patient associations in the fight against this disease, by organizing awareness and screening campaigns. These data will be used to guide public health policies in the pursuit of improved care and primary prevention.

Clinical outcomes of COVID-19 in patients with sickle cell disease in French Guiana.

Objectives: French Guiana also suffered concrete epidemiological consequences of the SARS-CoV2 epidemic. These regions are home to a large number of sickle cell patients who are at risk of developing severe forms of COVID-19. This study aimed to describe the characteristics and prognosis of patients with sickle disease infected with SARS-CoV2 during the first and second epidemic waves of 2020 in French Guiana. Design: We conducted a multicenter, retrospective cohort study that included sickle cell patients followed up in French Guiana. Results: Among the 79 patients infected with SARS-CoV2, there were 26 children <18 years. Forty-two patients were hospitalized and 37 were outpatients. Respiratory illness (38 %), vaso-occlusive crises (18 %), and acute chest syndrome (8 %) were the main causes of hospitalization. There were two cases of pulmonary embolism and one case of deep limb thrombosis. Seven patients were transferred to the ICU. Of these, three received mechanical ventilation, and two died. The deceased patients had the SS phenotype (a 16-year-old boy and a 32-year-old man), both of whom exhibited severe pneumonitis complicated by COVID-19. Conclusion: Despite the two deaths, the overall outcome was favorable.

Current obstetric outcomes in Jamaican women with sickle hemoglobinopathy - a balance of risks for aspirin?

OBJECTIVES: Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes. METHODS: A retrospective comparative analysis of HbSS, HbSC and HbSßThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted. RESULTS: Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSßThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5-32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4-16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1-8.9; p=0.037) and preterm birth (OR=2.6, 1.2-5.8; p=0.018) compared to HbSC and HbSßThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04-0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03-0.9, p=0.03)). CONCLUSIONS: HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes.

Unraveling DEHP influence on hemoglobin S polymerization in sickle cell disease: Ex vivo, in vitro and in silico analysis.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy, caused by a mutation at position 6 of the ß-globin chain and patients are frequently exposed to several blood transfusions in order to maintain physiological function. Transfusion blood bags are composed of PVC and phthalates (as DEHP) are often introduced to the material in order to confer malleability. In this sense, DEHP can easily elute to the blood and cause harmful effects. This study aimed to unravel DEHP effect on SCD patient's hemoglobin function. We found that HbS polymerization using whole erythrocytes is decreased by DEHP in ex vivo experiments and this effect might be mediated by the DEHP-VAL6 interaction, evaluated in silico. Isolated HbS exhibited less polymerization at low DEHP concentrations and increased polymerization rate at higher concentration. When analyzing the propensity to aggregate, HbS is more inclined to aggregate when compared to HbA due to the residue 6 mutation. Circular dichroism showed characteristic hemoglobin peaks for oxygenated HbS that are lost when oxygen is sequestered, and DEHP at higher concentration mildly recovers a peak close to the second hemoglobin one. Finally, by transmission electron microscopy we demonstrated that high DEHP concentration increased polymer formation with a more organized structure. These findings show for the first-time the beneficial effect of low-dose DEHP on HbS polymerization.

Sickle Cell Disease in Brazil: Current Management.

Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the ß-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other ß-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country.

Prevalence of arboviruses in sickle cell disease patients from two different regions of Brazil, the North and Northeast.

Sickle Cell Disease (SCD) is a hereditary disease characterized by extravascular and intravascular hemolysis and clinical variability, from mild pain to potentially life-threatening. Arboviruses include mainly Zika (ZIKV), Chikungunya (CHKV), and Dengue (DENV) virus, and are considered a public and social health problem. The present cross-sectional observational study aimed to investigate the prevalence of arbovirus infection in SCD patients from two Brazilian cities, Salvador and Manaus located in Bahia and Amazonas states respectively. A total of 409 individuals with SCD were included in the study, and 307 (75.06 %) patients tested positive for DENV-IgG, 161 (39.36 %) for ZIKV-IgG, and 60 (14.67 %) for CHIKV-IgG. Only one individual was positive for DENV-NS1 and another for DENV-IgM, both from Salvador. No individuals had positive serology for ZIKV-IgM or CHIKV-IgM. Arbovirus positivity by IgG testing revealed that the SCD group presented high frequencies in both cities. Interestingly, these differences were only statistically significant for ZIKV-IgG (p = 0.023) and CHIKV-IgG (p = 0.005) among SCD patients from Manaus. The reshaping of arbovirus from its natural habitat by humans due to disorderly urban expansion and the ease of international Mobility has been responsible for facilitating the spread of vector-borne infectious diseases in humans. We found the need for further studies on arboviruses in this population to elucidate the real association and impact, especially in acute infection. We hope that this study will contribute to improvements in the personalized clinical follow-up of SCD patients, identifying the influence of arbovirus infection in severe disease manifestations.

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/ß0, 7 S/ß+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P = 0.03) with stroke was found in HbS/ß-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r = -0.316; P < 0.001), age at first job (r = 0.221; P = 0.018), personal (r = 0.23; P = 0.012) and per capita familiar incomes (r = 0.303; P = 0.001), personal (r = 0.61; P = 0), maternal (r = 0.536; P = 0), and paternal educational status (r = 0.441; P = 0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

Fludarabine-Based Reduced-Intensity Conditioning Regimen for Hematopoietic Stem Cell Transplantation in a Pediatric Patient with Sickle Cell Disease: A Case Report.

Reduced-intensity conditioning (RIC) regimens have the potential to decrease toxicities related to hematopoietic stem cell transplantation (HCT) in patients with sickle cell disease (SCD). While initial results may have been acceptable in adults and young adults, there are no well-established strategies in children with SCD. Here, it is described the clinical course of two children with symptomatic SCD who have successfully undergone HSCT using Fludarabin-based conditioning.

Poor Sleep Quality in Jamaican Adults With Sickle Cell Disease: Prevalence, Risk Factors, and Association With Quality of Life.

Poor sleep and chronic illnesses have a bidirectional relationship where presence of one can worsen the other. Sickle cell disease (SCD) is associated with significant morbidity and early mortality. In this study, we examine sleep quality, its predictors, and its association with quality of life in Jamaican adults with SCD. This cross-sectional study evaluated 177 well adult SCD patients for sleep quality using The Pittsburgh Sleep Quality Index (PSQI) and quality of life using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Multiple linear regression models examined the predictors of poor sleep quality. The mean global PSQI score was 6.9 (SD 4.2) with 56.5% having poor sleep quality. Women had significantly worse scores for sleep efficiency (p 0.005), sleep latency (p 0.03) and higher use of sleeping medications (p 0.02). Those overweight/obese had significantly worse subjective sleep quality (p 0.001) and sleep efficiency (p 0.05). In multivariate regression analysis, overweight individuals had poorer sleep quality (OR: 2.9; 95% C.I.: 1.07, 7.88) than those with normal weight whereas those unemployed and looking for a job had lower prevalence of poor sleep quality (OR 0.2; 95% C.I.: 0.05, 0.77) compared to employed individuals. Participants with good sleep quality had significantly better functioning in all 5 domains of the ASCQ-Me. In conclusion, persons with SCD who are overweight or obese are at increased risk of poor sleep which can negatively affect quality of life. Patient populations and healthcare providers will need to manage the emerging burden of overweight/obesity.

Sickle cell disease and increased adverse maternal and perinatal outcomes in different genotypes.

BACKGROUND: Sickle cell disease (SCD) comprises a heterogeneous group of inherited hemolytic disorders that increases the risk of maternal and perinatal complications due to chronic systemic inflammatory response, endothelial damage and vaso-occlusion. The contribution of genotypes to the severity of outcomes during pregnancy is not completely established. METHODS: A retrospective study of medical charts was performed to compare maternal and perinatal outcomes in Hb SS, Hb SC disease and sickle-beta thalassemia (Hb Sß) pregnancies followed at a high-risk antenatal care unit over a 6-year period. A descriptive analysis of morphological findings was performed of the placenta when pathology reports were available. RESULTS: Sixty-two SCD pregnant women [25 Hb SS (40 %), 29 Hb SC (47 %) and 8 Hb Sß (13 %)] were included. Overall, SCD was associated with maternal complications (77 %), preterm birth (30 %), cesarean section (80 %) and a need of blood transfusion. In general there were no statistically significant differences between genotypes. The only significant difference was the hemoglobin level at first antenatal care visit which was lower for the homozygous genotype (7.7 g/dL) compared to Hb SC and Hb Sß (9.7 g/dL and 8.4 g/dL, respectively; p-value = 0.01). Ten of 15 evaluated placentas showed abnormal morphological findings CONCLUSION: SCD, regardless of the underlying genotype, is associated with increased adverse maternal and perinatal outcomes and placental abnormalities associated with maternal vascular malperfusion.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease

Abstract To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Real-world evidence of the burden of sickle cell disease: a 5-year longitudinal study at a Brazilian reference center.

INTRODUCTION: Sickle cell disease (SCD) is an inherited and multisystem blood disorder characterized by hemolytic anemia, vaso-occlusive crises (VOCs), progressive multiorgan damage and increased mortality. In Brazil, it is one of the most common monogenic diseases afflicting 60,000 to 100,000 individuals, however, there are sparse epidemiological data, as well as information on the utilization of public healthcare resources. METHOD: This was a 5-year (2016 - 2020) retrospective study conducted at one Brazilian reference center on SCD - Santa Casa de Sao Paulo, in Sao Paulo, Brazil. RESULTS: Among a total of 100 eligible adult patients, the median age was 31.0 years old, 84% of the patients were aged between 18 and 45 years old; 59% were women and 91% presented the genotype HbSS. The number of hematologist and non-hematologist visits at the outpatient unit were 2,198 and 1,436, respectively. The number of hospital ER visits was 758, of which 51% required 864 days of hospitalization. The main cause for seeking hospital medical care was the VOCs. The numbers and ratios of VOCs were: 1 to 10 VOCs, 64%; 11 to 20, 15%, and; 21 or more, 1%. There was a statistically significant difference between the number of VOCs and hospitalizations, as well as infection. CONCLUSION: Results indicate the burden of SCD on Brazilian patients' daily lives, the impact of VOCs on public healthcare resources, the importance of having a national surveillance program to improve resource utilization and clinical outcomes of patients with SCD and the urgent need for the revitalizing of the current national comprehensive SCD care programs.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort.

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.

Molecular characterisation of sickle cell disease and classification of major haplotypes associated with the ß-globin cluster (HBB gene) by means of SNP marker sequencing in a group of samples from Bolívar, Colombia.

BACKGROUND: Colombia has a mestizo population and the prevalence of haemoglobin variants varies according to each region, but heterozygous carriers can be found in all of them. AIM: To characterise sickle cell disease (SCD) haematologically, biochemically, and molecularly, and detect classic haplotypes by DNA sequencing in a group of samples from Bolívar, Colombia. SUBJECTS AND METHODS: Blood samples were collected after informed consent from volunteers from eight communities in the Bolívar department, plus samples from the Pacific region, Providencia Island, and Bogotá were included. Data were obtained from: (1) haematological analyses; (2) biochemical tests: dHPLC was used to determine haemoglobin (Hb); and (3) DNA sequencing data through five SNPs. RESULTS: 101 samples were identified by rs334 through Sanger's Sequencing, structural haemoglobinopathies HbAS (34.65%), HbSS (2.97%) and HbAC (1.98%) were found. When contrasting the Hb identification results between SNP rs334 Vs. dHPLC/Isoelectric Focusing (IEF), a coincidence was found in 39/43 samples analysed, therefore, when comparing these techniques, a significant correlation was found (Pearson's correlation coefficient r = 0.998). 26 samples previously analysed by rs334 were classified into classical haplotypes CAR (50.0%), BEN (30.76%), CAM (7.69%), SEN (3.84%), and ATP-I (7.69%). CONCLUSIONS: SCD characterisation and SNPs-based classification through Sanger's DNA sequencing have not been performed before in Colombia. The results of this work will make it possible to expand the data or records of carriers and those affected, which will benefit patients and their families.

Acupuncture as a Complementary Treatment for Leg Ulcers in Sickle-Cell Disease.

Background: Sickle-cell diseases (SCD) are a group of hereditary disorders in which a specific mutation in the gene that encodes the hemoglobin ß chain leads to formation of an anomalous hemoglobin molecule (HbS) with high polymerization power. This leads to sickling of erythrocytes in situations of low oxygen tension, such as in microcirculation, resulting in peripheral microvasculature occlusion, chronic hemolysis, inflammation, and damage to several target organs. Malleolar ulcers are among the most-debilitating complications of the disease, as they are associated with significant pain, secondary infections, and social impact due to their aesthetic impairment. There are no completely satisfactory therapeutic options for this complication; local healing agents, antibiotics, and dressings are used, with high rates of recurrence and complications, such as osteomyelitis and even limb amputation. Case: This case study evaluated the effect of Traditional Chinese Medicine techniques on chronic malleolar ulcers in a 49-year-old male patient. Ten sessions of systemic acupuncture (combinations involving Source, Master, Energetic Action, and Extraordinary Vessels points), auriculotherapy, and dressing with magnets were conducted. Results: Although the primary outcome sought was not reached (decrease in ulcer diameters), this patient had great reduction of local pain, a decrease in limb edema, and important reduction of his inflammatory condition, reflected in his decreasing blood levels of C-reactive protein. Conclusions: These results show that acupuncture should be considered as an important auxiliary treatment for SCD complications.