Follow-up of children with sickle cell anemia screened with transcranial Doppler and enrolled in a primary prevention program of ischemic stroke

ABSTRACT Background: Stroke is a serious complication of sickle cell anemia (SCA). The transcranial Doppler (TCD) is the risk-screening tool for ischemic strokes. The objective of the study was to describe the clinical progression of children with SCA who presented with high risk for stroke by TCD or relevant changes by magnetic resonance angiography (MRA) and underwent the regular transfusion program (RTP) and/or hydroxyurea (HU) treatment between 2007 and 2018. Method: This was a neonatal retrospective/prospective cohort study with children born between 1999 and 2014 with the homozygotic form (HbSS) or Sβ0-thalassemia who underwent TCD at least once. Results: Of the 718 children screened during this period, 675 had HbSS and 43 Sβ0-thalassemia. In 54 children (7.5%), all with HbSS, a high-risk TCD (n = 45) or, when the TCD was inconclusive, an MRA with cerebral vasculopathy (n = 9) was used for detection. Of these, 51 started the RTP and the families of three refused treatment. Of the 43 children with a highrisk TCD who initiated the RTP, 29 (67.4%) reverted to low risk. In 18 of them (62%), HU was started at the maximum tolerated dose (MTD) before transfusion discontinuation. None of these 29 patients had a stroke. Eight children (18.6%) maintained a high-risk TCD, even using the RTP/HU and two had a stroke. Conclusions: The TCD was confirmed as a viable tool for tracking patients with a risk for stroke. The RTP was effective in preventing the primary event. New strategies are necessary to prevent stroke using HU and new drugs, in addition to bone marrow transplantation.

A systematic review on hydroxyurea therapy for sickle cell disease in India

Background & objectives: Sickle cell disease (SCD) constitutes frequently inherited haemoglobin disorders and poses a significant health burden in India. Hydroxyurea (HU), the most commonly used drug, has shown promising results in the clinical management of SCD. The present systematic review was undertaken to assess the efficacy and toxicity of HU in Indian sickle cell patients. Methods: A systematic review of studies on HU therapy was conducted to identify the application of HU and its outcome(s) across India. PubMed, Scopus and Cochrane Library was used as data sources for various studies on the efficacy and toxicity of HU therapy for treatment for SCD in India published between January 2001 and October 2021. Two authors independently extracted the data on study design, patient characteristics and therapeutic outcomes of HU in order to determine the study quality of the present review. Results: Overall, 14 studies were included for a systematic analysis. Of these 11 were prospective, two cross-sectional and one double-blind randomized controlled trial. Low-dose HU (10 mg/kg/day) was found to reduce the rates of vaso-occlusive crisis and hospitalization as well as decreased the requirement of blood transfusion in SCD patients. The foetal haemoglobin (HbF) level was recorded in 13 (80%) studies all of whom reported an elevation in the HbF levels, with a mean increase in per cent HbF from 15.8 to 21.4 per cent across studies. The common adverse events were reversible, mild-to-moderate cytopenia and anaemia. Interpretation & conclusions: The findings of the present review suggest that there is still insufficient information presently to determine the long-term or major adverse effects on organ damage, fertility as well as pregnancy on the use of HU therapy for SCD. Long-term multi-centric studies are thus required to address these problems.

Impact of hydroxyurea on hospital stay & analgesic utilization in sickle cell anaemia with vaso-occlusive crises

Background & objectives: Hydroxyurea (HU) has been useful in preventing sickle cell vaso-occlusive crises (VOC). A few studies also suggest utility of HU, during acute VOC. Sickle cell anaemia (SCA) is of high prevalence in western districts of Odisha State, India, and VOC is a common presentation, despite being mostly of Arab-Indian haplotype. This study was undertaken to evaluate the impact of HU on hospital stay and analgesic utilization in acute painful VOC of SCA. Methods: Homozygous sickle cell disease (HbSS) patients were categorized as cases who were receiving low-dose HU (10 mg/kg/day) and patients who were not on HU were considered as control. Days of hospital stay, analgesic utilization and visual analogue scale (VAS) score in patients were compared with that of control. Analgesics used to control pain were tramadol hydrochloride, ketorolac and diclofenac. Results: A total of 359 homozygous sickle cell disease (SCD) patients with VOC were studied (187 patients and 172 controls). The patient group had lesser mean days of hospital stay (1.4 days less than controls, P<0.001) and required lesser days of analgesic utilization than controls (1.18 days less than controls, P<0.001). Significant differences were observed between patients and controls concerning VAS score and amount of tramadol hydrochloride, ketorolac and diclofenac utilization (P<0.05). Interpretation & conclusions: In this study, HU was found to have beneficial effects in acute VOC of homozygous SCD, which includes shortening the duration of hospital stay and reducing the net amount of analgesic utilization during hospitalization

Avaliação de prescrições pediátricas de hidroxiureia para pacientes com doença falciforme / Evaluation of pediatric hydroxyurea prescriptions for patients with sickle cell disease

A hidroxiureia (HU) constituiu um dos principais avanços no tratamento da doença falciforme. O uso do medicamento em crianças no Brasil ainda é off label e está disponível somente na forma farmacêutica sólida. O objetivo do presente trabalho é avaliar as estratégias de adaptação da forma farmacêutica sólida para o uso em crianças com doença falciforme. Trata-se de estudo descritivo, com análise de prescrições pediátricas de HU e aplicação de questionários aos responsáveis no período de janeiro a março de 2018. Foram analisadas 43 prescrições e identificadas duas formas de adaptação 1) diluição convencional: diluição do medicamento em quantidade pré-determinada de água, seguido de administração de parte da solução obtida (22) (51%) e 2) uso da recomendação posológica "holiday" ou intermitente (21) (49%). Todos os pacientes que utilizavam a estratégia de diluição convencional descartavam o restante do medicamento da rede de esgoto doméstica. Além disso, identificou-se administração incorreta do medicamento em um paciente. A falta de forma farmacêutica apropriada para população pediátrica pode levar a riscos de administração incorreta e gastos desnecessários com o descarte de medicamentos, além de descarte inadequado que compromete fatores ambientais. O estudo reforça a necessidade de desenvolvimentos de formas farmacêuticas mais adequadas ao público infantil.

Hydroxyurea (HU) was one of the main advances in the treatment of sickle cell disease. The use of the drug in children in Brazil is still off-label and is only available in solid pharmaceutical form. The objective of the present study is to evaluate the strategies for adapting the solid dosage form for use in children with sickle cell disease. This is a descriptive study, with the analysis of pediatric HU prescriptions and the application of questionnaires to those responsible in the period from January to March 2018. 43 prescriptions were analyzed, and two forms of adaptation were identified, 1) conventional dilution: dilution of the drug in a pre-prescribed quantity - determined amount of water, followed by administration of part of the solution obtained (22) (51%), and 2) use of the holiday or intermittent dose recommendation (21) (49%). All patients using the conventional dilution strategy discarded the remainder of the drug from the domestic sewage system. In addition, incorrect administration of the drug was identified in one patient. The lack of an appropriate pharmaceutical form for the pediatric population can lead to risks of incorrect administration and unnecessary expenses with drug disposal, in addition to improper disposal that compromises environmental factors. This study reinforces the need to develop pharmaceutical forms that are more suitable for children.

IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to hydroxyurea in essential thrombocythemia / 医学前沿

The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

Technical specification for clinical diagnosis and treatment of human parvovirus B19 infection in kidney transplant recipients (2022 edition) / 器官移植

Long-term use of immunosuppressant in kidney transplant recipients leads to poor immune function and infection with various pathogens. In recent years, along with the advancement of detection technique of human parvovirus B19 (HPV-B19) infection and the increasing quantity of kidney transplantation, the infection rate of HPV-B19 after kidney transplantation has been elevated year by year, becoming one of the major causes of pure red cell aplasia (PRCA), affecting the recovery of renal allograft function, and even leading to the injury or poor prognosis of renal allograft. To further standardize the diagnosis and treatment of HPV-B19 infection in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association and National Kidney Transplantation Quality Control Center jointly organized experts to formulate the clinical diagnosis and treatment specification for HPV-B19 infection after kidney transplantation from the perspectives of etiology, epidemiological characteristics, clinical manifestations, diagnosis, prevention, treatment, existing problems and prospects of HPV-B19, aiming to provide guidance for standardized prevention and treatment of HPV-B19 infection post-kidney transplantation in China.

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

ABSTRACT Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18-69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5-2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5-2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.

Evaluación nutricional de pacientes en edad pediátrica con drepanocitosis tratados con hidroxiurea / Nutritional Evaluation of Pediatric Patients with Sickle Cell Disease Treated with Hydroxyurea

RESUMEN Fundamento: estudios clínicos en pacientes con drepanocitosis han demostrado que el uso de hidroxiurea se asocia a una reducción de complicaciones agudas y crónicas, incluyendo las relacionadas con el estado nutricional de estos pacientes. Objetivo: evaluar el estado nutricional en pacientes con drepanocitosis tratados con hidroxiurea en el Hospital Pediátrico Universitario Paquito González Cueto de Cienfuegos. Métodos: se realiza un estudio descriptivo, analítico y prospectivo de la totalidad de los pacientes con drepanocitosis tratados con hidroxiurea, atendidos en el Servicio de Hematología del Hospital Pediátrico de Cienfuegos en el periodo de enero 2012 a diciembre 2018. Las variables del estudio fueron: edad, sexo, variante de hemoglobina, manifestaciones clínicas y evaluación nutricional, parámetros hematológicos, hospitalizaciones y requerimientos transfusionales. La información se obtuvo de los expedientes clínicos. Resultados: se estudiaron 15 pacientes, hubo predomino del sexo femenino (60 %) y los adolescentes representaron el 80 % de los pacientes en estudio. Presentaban la forma homocigota 10 pacientes (66,7 %); la variante Sβ talasemia y SC estuvo representada con 2 y 3 pacientes, respectivamente. No hubo diferencias significativas al comparar los valores hematológicos antes y después del tratamiento. Se observó una disminución en la frecuencia y gravedad de las crisis, en el número de hospitalizaciones y requerimientos transfusionales en la totalidad de los pacientes. La desnutrición estuvo presente en solo 4 pacientes del total. Conclusiones: el tratamiento con hidroxiurea para los pacientes en estudio resultó en mejoría clínica, reducción del número de ingresos y disminución de los requerimientos transfusionales, lo cual repercutió favorablemente en su estado nutricional.

ABSTARCT Background: clinical studies in patients with sickle cell disease have shown that the use of hydroxyurea is associated with a reduction in acute and chronic complications, including those related to the nutritional status of these patients. Objective: to evaluate the nutritional status in patients with sickle cell disease treated with hydroxyurea at the Paquito González Cueto University Pediatric Hospital in Cienfuegos. Methods: a descriptive, analytical and prospective study was carried out of all the patients with sickle cell disease treated with hydroxyurea, treated at the Hematology Service of the Pediatric Hospital of Cienfuegos in the period from January 2012 to December 2018. The study variables were: age, sex, hemoglobin variant, clinical manifestations and nutritional evaluation, hematological parameters, hospitalizations and transfusion requirements. The information was obtained from the clinical records. Results: 15 patients were studied, there was a predominance of females (60 %) and adolescents represented 80 % of the patients in the study. 10 patients (66.7 %) presented the homozygous form; the Sβ thalassemia and SC variant were represented with 2 and 3 patients, respectively. There were no significant differences when comparing hematological values ​​before and after treatment. A decrease was observed in the frequency and severity of the seizures, in the number of hospitalizations and transfusion requirements in all the patients. Malnutrition was present in only 4 patients out of the total. Conclusions: treatment with hydroxyurea for the study patients resulted in clinical improvement, reduction in the number of admissions and decrease in transfusion requirements, which favorably affected their nutritional status.

Chronic osteo-articular changes in patients with sickle cell disease

Abstract Background: Sickle cell disease (SCD) is an autosomal recessive genetic disease in which a mutation occurs in the β-globin chain gene, resulting in abnormal hemoglobin levels. In an environment with reduced oxygen concentration, red blood cells change their conformation, resulting in chronic hemolysis and consequent anemia and vaso-occlusive crises with injuries to several organs, with a significant impairment of the osteoarticular system. This study aimed to verify the chronic osteoarticular alterations and their association with clinical and laboratory characteristics of patients with SCD with a more severe phenotype (SS and Sβ0), on a steady-state fasis. Methods: Fifty-five patients were referred to a medical consultation with a specialized assessment of the locomotor system, followed by laboratory tests and radiographic examinations. Results: In total, 74.5% patients had hemoglobinopathy SS; 67.3% were female; and 78.2% were non-whites. The mean patient age was 30.5 years. Most patients (61.8%) reported up to three crises per year, with a predominance of high-intensity pain (65.5%). Radiographic alterations were present in 80% patients. A total of 140 lesions were identified, most which were located in the spine, femur, and shoulders. Most lesions were osteonecrosis and osteoarthritis and were statistically associated with the non-use of hydroxyurea. Conclusions: There was a high prevalence of chronic osteoarticular alterations, which was statistically associated only with the non-regular use of hydroxyurea.(AU)

Study of sensitization effect of hydroxyurea on chemoradiotherapy of human glioma U251 cells / 中华放射肿瘤学杂志

Objective:To investigate the effect of hydroxyurea (HU) combined with temozolomide (TMZ) and radiotherapy (RT) on the sensitivity of human glioma U251 cells to chemoradiotherapy (CRT).Methods:Human glioma U251 cell line was cultured in vitro. CCK8 cell assay was used to detect the proliferation activity of U251 cells treated with different concentrations of HU/TMZ under different conditions. Flow cytometry was utilized to detect apoptosis rate and cell cycle distribution of U251 cells. Transwell chamber assay and scratch test were performed to evaluate the changes of cell invasion and migration. The expression levels of apoptosis proteins were determined by Western blot. Colony formation assay was adopted to detect the cell survival fraction . Results:HU concentration at 50μmol/L and below did not affect the proliferation of human glioma U251 cells ( P>0.05). Low-dose HU combined with CRT significantly inhibited cell proliferation ( P<0.05), invasion ( P<0.01) and migration (12h P<0.001, 24h P<0.01), and promoted cell apoptosis ( P<0.01) compared with the use of CRT alone. Application of 50μmol/L HU combined with RT increased the radiosensitivity of cells (SER=1.49), significantly prolonged the cell cycle of S phase and G 2 phase (both P<0.05), considerably up-regulated the expression levels of the apoptosis-associated proteins of Caspase-3 and Bax and significantly down-regulated the expression level of anti-apoptosis protein of Bcl-2(all P<0.001). Conclusions:Compared with CRT, HU combined with CRT can further inhibit the proliferation, invasion and migration of human glioma U251 cells, promote cell apoptosis, increase the radiosensitivity and prolong the cell cycle of S and G 2 phases, thereby enhancing the sensitivity of human glioma U251 cells to CRT.

Effects of oxidative stress on liver, brain and spinal cord of rats using L-NAME and treated with hydroxyurea. A model of sickle cell complication

Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

Pregnancy with chronic myeloid leukemia: case report and literature review

Chronic myeloid leukemia (CML) is a rare condition during reproductive age. Still, women may present with pre-existing or newly diagnosed CML during pregnancy. The management of chronic myeloid leukemia during pregnancy requires balancing the well-being of the mother with that of fetus. Tyrosine Kinase inhibitors are considered the most effective drug against CML but they are still not considered safe during pregnancy and breast feeding. So, there is a need for management of CML with alternate drugs during pregnancy. Here we report a case of a 26-year-old lady who was diagnosed with chronic myelogenous leukemia (CML) at 20 weeks of gestation and had an atypical chromosome translocation t (9:22). She was managed jointly by obstetrician and haemato-oncologist for the remainder of her pregnancy and eventually she delivered a healthy baby at term.

Clinical difference between identical twins with sickle cell anemia / Diferenças clínicas entre gêmeas idênticas com anemia falciforme

ABSTRACT Sickle cell anemia (SCA) is a genetic disease that causes important clinical manifestations due to chronic hemolysis and vascular occlusion. The aim of this study was to report a rare case of monozygotic twins diagnosed with SCA, presenting a different clinical characteristic. An interview with the patients was carried out and the medical records were consulted. One patient has a history of malleolar ulcer in the left back, while the other does not. Both patients used hydroxyurea at the same dosage. This study shows that SCA presents, in addition to genetic factors, non-genetic factors involved in the severity of the disease and its clinical manifestations. Studies are needed that may contribute to the understanding of the clinical heterogeneity of SCA.

RESUMEN La anemia de células falciformes (ACF) es una enfermedadgenética que causa importantes manifestaciones clínicas debido a la anemia hemolítica crónica y a la oclusión vascular. El objetivo de este estudio fue reportar un caso raro de gemelas monocigóticas con diagnóstico de ACF, presentando una característica clínica diferente. Se realizó una entrevista con las pacientes, consultándose sus fichas médicas. Una paciente tiene historia de úlcera maleolar en la región izquierda, mientras la otra no. Ambas hacían tratamiento con hidroxiurea en la misma dosis. Este estudio demuestra que la ACF presenta, además de factores genéticos, factores no genéticos involucrados en la severidadde la enfermedad y sus manifestaciones clínicas. Son necesarios estudios que contribuyan para la comprensión de la heterogeneidad clínica de la ACF.

RESUMO A anemiafalciforme (AF) é uma doença genética que causa importantes manifestações clínicas devido à hemólise crônica e à oclusão vascular. O objetivo deste estudo foi relatar um caso raro de gêmeas univitelinas com diagnóstico de AF, apresentando uma característica clínica diferente. Uma entrevista com as pacientes foi realizada, e os prontuários foram consultados. Uma paciente tem história de úlcera maleolar na região esquerda, enquanto a outra não. Ambas as pacientes faziam tratamento com hidroxiureia na mesma dosagem. Este estudo mostra que a AF apresenta, além de fatores genéticos, fatores não genéticos envolvidos na gravidade da doença e suas manifestações clínicas, sendo necessários estudos quepossam contribuir para o entendimento da heterogeneidade clínica da AF.

Management of chronic myeloid leukemia during pregnancy: a retrospective analysis at a single center

ABSTRACT We analyzed the management and outcomes of pregnancies of patients with chronic myeloid leukemia at a single center over fifteen years. Among the 203 CML female patients, there were ten pregnancies in seven women, all of them not planned. In three cases, the chronic myeloid leukemia diagnosis was made during pregnancy. Five patients received tyrosine kinase inhibitors in the first weeks of pregnancy and the drug was interrupted until delivery. One patient lost complete cytogenetic response, and two patients lost the hematological response. A patient with a stable major molecular response had two successful pregnancies without loss of response. There were four premature births. There were no maternal adverse events, fetal malformation or death. All patients received Interferon-alpha during gestation, and two received hydroxyurea for a short period. Leukapheresis was performed in two patients for hyperleukocytosis control. One patient with sickle cell disease died from disease progression six months after delivery. Conclusions: The tyrosine kinase inhibitors ministration should be interrupted during pregnancy. Patients should be advised to achieve a stable and deep molecular response if they plan to conceive, to avoid the risk of disease progression.

The Effect of Hydroxyurea Therapy on Adverse Clinical Events and Haematological Indices in Paediatric Patients with Sickle Cell Anaemia / Efecto de la Terapia con Hidroxiurea en los Eventos Clínicos Adversos y los Indices Haematológicos de Pacientes Paediátricos con Aanemia de Células Falciformes

ABSTRACT Objective: The aim of this study was to determine the effect of hydroxyurea on adverse clinical events and haematological indices in paediatric patients with sickle cell anaemia. Method: This study compared the same cohort of patients before and after hydroxyurea therapy, monitoring the rate of adverse events, pre- and post-treatment and haematological indices. Results: Of the 40 patients, the incidence rate of painful crises post-treatment was 80% lower than pre-treatment. Post-treatment incidence rates of painful crises managed at home, requiring emergency department care or requiring admission to the ward were also lower - 79%, 81% and 84%, respectively. There was no significant difference in the incidence of other clinical events. The haemoglobin concentration increased within the first month and plateaued while the mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) continued to increase until six months before plateauing out. The white blood cell count (WBC) and absolute neutrophil count (ANC) decreased over the first month before levels stabilized. The reticulocyte percentage and the absolute reticulocyte count (ARC) decreased over the first three months before plateauing while the platelet count remained stable. Conclusion: Hydroxyurea significantly reduced the incidence of painful crises. There were significant increases in haemoglobin, MCV and MCHC with decreases in WBC, ANC, ARC, and reticulocyte percentage while the platelet count remained relatively stable.

RESUMEN Objetivo: El objetivo de este estudio fue determinar el efecto de la hidroxiurea sobre los eventos clínicos adversos y los índices hematológicos en pacientes pediátricos con anemia falciforme. Método: Este estudio comparó una misma cohorte de pacientes antes y después del tratamiento con hidroxiurea, monitoreando la tasa de eventos adversos, el tratamiento previo y posterior, y los índices hematológicos. Resultados: En los 40 pacientes, la tasa de incidencia de postratamiento de crisis dolorosas fue 80% inferior a la del pretratamiento. Las tasas de incidencia de postratamientos de crisis dolorosas que fueron tratadas en el hogar, atendidas en el departamento de emergencias, o requirieron ingreso hospitalario, fueron también menores -79%, 81%y 84%, respectivamente. No hubo diferencias significativas en la incidencia de otros eventos clínicos. La concentración de hemoglobina aumentó en el primer mes y se estabilizó, mientras que el volumen corpuscular medio (VCM) y la concentración de hemoglobina corpuscular media (CHCM) continuaron aumentando hasta seis meses antes de estabilizarse. nivelarse. El conteo de glóbulos blancos (CGB) y el conteo absoluto de neutrófilos (CAN) disminuyeron durante el primer mes antes de que los niveles se estabilizaran. El porcentaje de reticulocitos y el conteo absoluto de reticulocitos (CAR) disminuyeron durante los primeros tres meses antes de estabilizarse, mientras que el conteo de plateletas permaneció estable. Conclusión: La hidroxiurea redujo significativamente la incidencia de crisis dolorosas. Hubo aumentos significativos de hemoglobina, VCM y CHCM con disminuciones de CGB, CAN, CAR, y porcentaje de reticulocitos mientras que el conteo plaquetario permaneció relativamente estable.

Carotid and femoral intima-media thickness in adults with sickle cell disease

Background: This study was conducted to evaluate Carotid Intima Media Thickness (CIMT) and Femoral Intima Media Thickness (FIMT) in adults with SCD.Methods: The present prospective cross-sectional study with control group was carried out in Department of Medicine at Acharya Vinoba Bhave rural hospital over a period of 6months from January to June 2018. A total of 100 (50 cases of SCD, 50 normal subjects) were studied. In the SCD group, 35 cases were patients regular follow up cases and 15 patients were in sickle cell crisis. CIMT of both left and right carotids were taken and the mean of the two values were recorded. The IMT was also measured in the right common femoral artery (RCFA) and left common femoral artery.Results: SCD patients in steady state had significantly decreased Hb%, increased WBC counts and platelet counts as compared to healthy controls. The mean right FIMT, left FIMT, right CIMT and left CIMT the patients with SCD with crisis were significantly higher than that of the patients without SCD (P<0.001). One way showed that there were significant differences in duration of disease in mean level of Hb%, WBC count, platelet count of the patients in the three groups (p<0.01).Conclusions: CIMT and FIMT can pick up the macrovascular involvement early and can be utilized as screening tools to predict vascular injury so that at risk individuals would be subjected to proper treatment protocols, especially hydroxyurea therapy early on.

Higher values of triglycerides: HDL-cholesterol ratio hallmark disease severity in children and adolescents with sickle cell anemia

Dyslipidemia has been described in sickle cell anemia (SCA) but its association with increased disease severity is unknown. Here, we examined 55 children and adolescents with SCA as well as 41 healthy controls to test the association between the lipid profiles in peripheral blood and markers of hemolysis, inflammation, endothelial function, and SCA-related clinical outcomes. SCA patients exhibited lower levels of total cholesterol (P<0.001), low-density lipoprotein cholesterol (LDL-c) (P<0.001), and high-density lipoprotein cholesterol (HDL-c) (P<0.001), while displaying higher triglyceride (TG) levels and TG/HDL-c ratio values (P<0.001). TG/HDL-c values were positively correlated with lactate dehydrogenase (P=0.047), leukocyte count (P=0.006), and blood flow velocity in the right (P=0.02) and left (P=0.05) cerebral artery, while being negatively correlated with hemoglobin levels (P<0.04). Acute chest syndrome (ACS) and vaso-occlusive events (VOE) were more frequent in SCA patients exhibiting higher TG/HDL-c values (odds ratio: 3.77, P=0.027). Multivariate logistic regression analysis confirmed independent associations between elevated TG/HDL-c values and SCA. Thus, children and adolescents with SCA exhibited a lipid profile associated with hemolysis and inflammatory parameters, with increased risk of ACS and VOE. TG/HDL-c is a potential biomarker of severity of disease.

Evaluation of hydroxyurea genotoxicity in patients with sickle cell disease / Avaliação da indução de genotoxicidade pela hidroxiureia em pacientes com doença falciforme

ABSTRACT Objective To evaluate the induction of DNA damage in peripheral blood mononuclear cells of patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea. Methods The study subjects were divided into two groups: one group of 22 patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea, and a Control Group composed of 24 patients with sickle cell disease who were not treated with hydroxyurea. Peripheral blood samples were submitted to peripheral blood mononuclear cell isolation to assess genotoxicity by the cytokinesis-block micronucleus cytome assay, in which DNA damage biomarkers - micronuclei, nucleoplasmic bridges and nuclear buds - were counted. Results Patients with sickle cell disease treated with hydroxyurea had a mean age of 25.4 years, whereas patients with sickle cell disease not treated with hydroxyurea had a mean age of 17.6 years. The mean dose of hydroxyurea used by the patients was 12.8mg/kg/day, for a mean period of 44 months. The mean micronucleus frequency per 1,000 cells of 8.591±1.568 was observed in the Hydroxyurea Group and 10.040±1.003 in the Control Group. The mean frequency of nucleoplasmic bridges per 1,000 cells and nuclear buds per 1,000 cells for the hydroxyurea and Control Groups were 0.4545±0.1707 versus 0.5833±0.2078, and 0.8182±0.2430 versus 0.9583±0.1853, respectively. There was no statistically significant difference between groups. Conclusion In the study population, patients with sickle cell disease treated with the standard dose of hydroxyurea treatment did not show evidence of DNA damage induction.

RESUMO Objetivo Avaliar o efeito da indução de danos ao DNA em células monocelulares do sangue periférico de pacientes com doença falciforme, genótipos SS e SC, tratados com hidroxiureia. Métodos Os sujeitos da pesquisa foram divididos em dois grupos: um de 22 pacientes com doença falciforme genótipos SS e SC tratados com hidroxiureia, e o outro controle, composto por 24 pacientes com doença falciforme que não eram tratados com o fármaco. As amostras de sangue periférico foram submetidas ao isolamento de células mononucleares do sangue periférico para avaliação da genotoxicidade pelo ensaio de micronúcleo citoma com bloqueio da citocinese, tendo sido quantificados os biomarcadores de danos ao DNA - micronúcleos, pontes nucleoplasmáticas e brotamento nuclear. Resultados Os pacientes com doença falciforme tratados com hidroxiureia apresentaram média de idade de 25,4 anos, enquanto aqueles com doença falciforme não tratados com hidroxiureia tiveram média de idade de 17,6 anos. A dose média de hidroxiureia utilizada pelos pacientes foi de 12,8mg/kg/dia, por período médio de 44 meses. A frequência média de micronúcleos por 1.000 células de 8,591±1,568 foi observada no Grupo Hidroxiureia e de 10,040±1,003 no Grupo Controle. Adicionalmente, a frequência média de pontes nucleoplasmáticas por 1.000 células e brotamento nuclear por 1.000 células para o Grupo Hidroxiureia e Controle foi de 0,4545±0,1707 versus 0,5833±0,2078, e de 0,8182±0,2430 versus 0,9583±0,1853, respectivamente. Não houve diferença estatisticamente significativa entre os grupos. Conclusão Na população estudada de pacientes com doença falciforme com tratamento em dose padrão de hidroxiureia, não houve evidência de indução de danos ao DNA.

Fenotipificación de un caso de anemia de células falciformes / Elucidating the phenotype in a sickle cell disease case

La anemia de células falciformes es una enfermedad genética frecuente en la que la herencia de dos genes mutantes de la hemoglobina, uno de cada progenitor, produce un trastorno de la hemoglobina. Es una enfermedad crónica con exacerbaciones agudas que causan efectos a largo plazo en la educación, la vida familiar, la integración social y la calidad de vida del paciente. La clínica se resume en vaso oclusión e isquemia tisular, anemia hemolítica y la susceptibilidad a infecciones. Se presenta el caso de un hombre de raza negra, de 28 años cursando con crisis dolorosa vaso-oclusiva, trastorno hemolítico y síndrome anémico de volúmenes normales.

Sickle cell anemia is a common genetic disease in which the inheritance of two mutant hemoglobin genes, one from each parent produces a hemoglobinopathy. It is a chronic disease with acute exacerbations that cause long-term effects on education, family life, social integration and the patient's quality of life. The clinic is summarized in vaso-occlusion and tissue ischemia, hemolytic anemia and susceptibility to infections. We present the case of a 28 years old black male, suffering from a vaso-occlusive crisis, hemolytic disorder and normocytic anemic syndrome.