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2.
Transfusion ; 61(8): 2290-2294, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34252204

RESUMO

BACKGROUND: Irradiation of blood products prevents transfusion-associated graft-versus-host disease, but most patients do not require this modification which could have an adverse impact on transfusion outcomes. We hypothesized that irradiation may increase transfusion requirements for patients with sickle cell disease (SCD) receiving chronic transfusion. STUDY DESIGN AND METHODS: Our pediatric hospital implemented a new policy of universal blood product irradiation in May 2018. We conducted a retrospective chart review of patients with SCD receiving chronic red blood cell (RBC) transfusion throughout the year before and after institution of this policy. The primary outcome was the change in RBC transfusion volume per patient weight transfused during the pre- vs. post- universal irradiation period. Secondary outcomes were the change in median pretransfusion laboratory values. RESULTS: Among 17 patients, 8 (47%) received more RBCs the year before irradiation and 9 (53%) received more the year after irradiation. Implementation of universal irradiation did not significantly increase transfusion volumes needed to clinically manage this population (median change +1.7 ml/kg/year, p = .54). Additionally, there were no significant changes in absolute reticulocyte count, hemoglobin, hemoglobin S%, white blood cell count, lactate dehydrogenase, total bilirubin, serum potassium, and ferritin during the two time periods. CONCLUSION: In a cohort of patients with SCD receiving simple chronic transfusion, irradiation did not impact transfusion requirements or pertinent pretransfusion laboratory values. Irradiation does not appear to have clinically significant consequences for SCD chronic transfusion management.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Adolescente , Anemia Falciforme/sangue , Criança , Pré-Escolar , Transfusão de Eritrócitos/efeitos adversos , Feminino , Raios gama , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
3.
Transfusion ; 61(8): 2255-2264, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34002408

RESUMO

BACKGROUND: Patients with sickle cell disease (SCD) are frequent recipients of red blood cell (RBC) transfusions and are at risk for RBC alloimmunization. RBC alloimmunization is diagnosed by identifying RBC alloantibodies as part of pre-transfusion testing, but this testing fails to detect alloantibodies that have evanesced. It may be beneficial to screen for new RBC alloantibody development after transfusion before possible antibody evanescence. STUDY DESIGN AND METHODS: Our institution started a new initiative for episodically transfused patients with SCD to obtain at least one antibody screen 2-6 months after transfusion as part of their clinical care. A database was created to prospectively track all transfused patients for 1 year and their post-transfusion antibody screen results. Patients received prophylactically CEK-matched RBC units. RESULTS: During the study year, 138 patients with SCD received a total of 242 RBC transfusions. Patients with a history of an RBC alloantibody (n = 13, 9.4%) had previously received more RBC units than non alloimmunized patients (median 11 vs. 2 RBC units, p = .0002). A total of 337 post-transfusion antibody screens were obtained in 127 patients (92.0%) with 110 patients (79.7%) having at least one antibody screen 2-6 months post-transfusion. With this prospective testing, two new RBC alloantibodies (anti-C and -M) were identified in two patients. CONCLUSION: It is feasible to test for new RBC alloantibody development in most episodically transfused patients with SCD as part of their routine care. The yield of this screening appears low with CEK matching, but it could still provide important information for individual patients.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos , Eritrócitos/imunologia , Isoanticorpos/imunologia , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/imunologia , Criança , Pré-Escolar , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/métodos , Feminino , Humanos , Isoanticorpos/sangue , Masculino , Estudos Prospectivos
5.
Biochem Biophys Res Commun ; 554: 222-228, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33823382

RESUMO

Optical folding and rotation behavior of red blood cells (RBCs) in polarized laser tweezers are considerably important for understanding the biophysical and biomechanical properties using the fast probing method. Here, a dual-mode polarized single-laser tweezers technique with distinct principal axes exhibiting different polarization states is presented and designed to investigate the deformation, optical folding, and rotation of single living cells with one measurement. RBC optical folding and rotation speed are measured in patients with sickle cell disease (SCD), including follow up of patients after hydroxyurea (HU) treatment for at least three months. Folding angle and rotation speed are significantly lower in patients with SCD and do not significantly differ in patients treated by HU compared with the healthy control group. The RBC folding angle and rotation speed in patients treated with HU drug increase linearly at lower laser powers and rapidly at higher powers, and increase much slowly in patients not treated with HU. The difference in the folding angle and rotation speed of RBCs could be useful for drug response in SCD or predicting pain crisis in SCD.


Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Eritrócitos/fisiologia , Hidroxiureia/administração & dosagem , Anemia Falciforme/metabolismo , Antidrepanocíticos/administração & dosagem , Biomarcadores/análise , Estudos de Casos e Controles , Contagem de Eritrócitos , Eritrócitos/efeitos da radiação , Feminino , Humanos , Lasers , Masculino , Pinças Ópticas , Rotação , Resultado do Tratamento
6.
BMC Infect Dis ; 21(1): 329, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827455

RESUMO

BACKGROUND: In Plasmodium falciparum infection, clinical conditions such as anaemia, thrombocytopenia and leukocytosis are common. Mutation in haemoglobin sub-unit beta gene (HBB) may be a genetic factor responsible for these haematological changes during infection. However, the contributions of the carriage of different HBB genotypes on these changes remain largely unknown. METHODOLOGY: In this cross-sectional study, we evaluated haematological abnormalities in P. falciparum-infected children (n = 217, aged 1-192 months) with different haemoglobin sub-unit beta (HBB) genotypes (HbAA, HbAS and HbSS). Children with acute febrile conditions were recruited at Jaramogi Oginga Odinga Teaching and Referral Hospital at the outpatient clinic. Haematological parameters were determined using Beckman Coulter counter ACTdiff2™ while HBB genotyping was done using TaqMan® SNP genotyping assay. Chi-square (χ2) was used to determine differences between proportions. Differences in haematological parameters were compared across groups using Kruskal Wallis test and between groups using Mann Whitney U test. Partial correlation test was used to determine correlation between haematological parameters and sickle cell genotypes while controlling for age and sex. RESULTS: Haemoglobin (Hb), [median (IQR); 7.3 (1.3), P = 0.001], haematocrit (HCT), [median (IQR); 26.4 (4.4), P = 0.009], red blood cells (RBC), [median (IQR); 3.2 (1.7), P = 0.048] were markedly reduced in HbSS, however, red cell distribution with (RDW) [median (IQR); 14.9 (3.3), P = 0.030] was increased in malaria infected children with HbSS. Severe anaemia was highest in HbSS (23.1%) followed by HbAA (8.6%) and HbAS (7.1%). There were no differences in platelet count (P = 0.399) hence no severe thrombocytopeania across the genotypes. Leukocytosis was highest in HbSS (69.2%), 42% in HbAS and 31% in HbAA. The RBC, HCT and Hb had negative correlation with RDW in HbSS in malarial-infected children (r = - 0.725, P = 0.008), (r = - 0.718, P = 0.009) and (r = - 0.792, P = 0.002), respectively. CONCLUSION: Our study reveals that anaemia is the most common abnormality in malaria-infected children with carriage of HbSS. The RBC, HCT and Hb concentration decrease with increase in RDW levels in infected children with carriage of HbSS compared to other HBB genotypes. Therefore, carriage of HbSS genotype is correlated with severity of haematological abnormalities.


Assuntos
Anemia Falciforme/sangue , Malária Falciparum/sangue , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/genética , Criança , Pré-Escolar , Estudos Transversais , Contagem de Eritrócitos , Feminino , Genótipo , Hematócrito , Hemoglobinas/genética , Humanos , Lactente , Quênia , Leucocitose , Malária Falciparum/complicações , Malária Falciparum/genética , Masculino , Contagem de Plaquetas
7.
Ann Hematol ; 100(6): 1401-1409, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33796899

RESUMO

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.


Assuntos
Injúria Renal Aguda/sangue , Anemia Falciforme/sangue , Lipocalina-2/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lipocalina-2/urina , Masculino , Curva ROC
8.
Cells ; 10(2)2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672679

RESUMO

(1) Background: It is known that sickle cells contain a higher amount of Ca2+ compared to healthy red blood cells (RBCs). The increased Ca2+ is associated with the most severe symptom of sickle cell disease (SCD), the vaso-occlusive crisis (VOC). The Ca2+ entry pathway received the name of Psickle but its molecular identity remains only partly resolved. We aimed to map the involved Ca2+ signaling to provide putative pharmacological targets for treatment. (2) Methods: The main technique applied was Ca2+ imaging of RBCs from healthy donors, SCD patients and a number of transgenic mouse models in comparison to wild-type mice. Life-cell Ca2+ imaging was applied to monitor responses to pharmacological targeting of the elements of signaling cascades. Infection as a trigger of VOC was imitated by stimulation of RBCs with lysophosphatidic acid (LPA). These measurements were complemented with biochemical assays. (3) Results: Ca2+ entry into SCD RBCs in response to LPA stimulation exceeded that of healthy donors. LPA receptor 4 levels were increased in SCD RBCs. Their activation was followed by the activation of Gi protein, which in turn triggered opening of TRPC6 and CaV2.1 channels via a protein kinase Cα and a MAP kinase pathway, respectively. (4) Conclusions: We found a new Ca2+ signaling cascade that is increased in SCD patients and identified new pharmacological targets that might be promising in addressing the most severe symptom of SCD, the VOC.


Assuntos
Anemia Falciforme/sangue , Sinalização do Cálcio , Eritrócitos/metabolismo , Lisofosfolipídeos/metabolismo , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo N/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Células HeLa , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Modelos Biológicos , Proteína Quinase C/metabolismo , Canal de Cátion TRPC6/metabolismo , Doadores de Tecidos
9.
Science ; 371(6533): 1019-1025, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674488

RESUMO

In vivo models that recapitulate human erythropoiesis with persistence of circulating red blood cells (RBCs) have remained elusive. We report an immunodeficient murine model in which combined human liver and cytokine humanization confer enhanced human erythropoiesis and RBC survival in the circulation. We deleted the fumarylacetoacetate hydrolase (Fah) gene in MISTRG mice expressing several human cytokines in place of their murine counterparts. Liver humanization by intrasplenic injection of human hepatocytes (huHep) eliminated murine complement C3 and reduced murine Kupffer cell density. Engraftment of human sickle cell disease (SCD)-derived hematopoietic stem cells in huHepMISTRGFah -/- mice resulted in vaso-occlusion that replicated acute SCD pathology. Combined liver-cytokine-humanized mice will facilitate the study of diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, and malaria, and also preclinical testing of therapies.


Assuntos
Anemia Falciforme/sangue , Circulação Sanguínea , Modelos Animais de Doenças , Eritrócitos/citologia , Eritropoese/fisiologia , Camundongos , Animais , Citocinas/metabolismo , Eritropoese/genética , Feminino , Deleção de Genes , Células-Tronco Hematopoéticas/citologia , Humanos , Hidrolases/genética , Fígado/fisiologia , Camundongos Mutantes , Pessoa de Meia-Idade
10.
Transfusion ; 61(6): 1694-1698, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33660875

RESUMO

INTRODUCTION: The contribution of coagulation activation to the pathogenesis of sickle cell disease (SCD) remains incompletely defined. We evaluated the efficacy and safety of rivaroxaban, an oral direct factor Xa inhibitor, in subjects with sickle cell anemia. MATERIALS AND METHODS: In this pilot, single-center, randomized, double-blind, placebo-controlled, crossover study, eligible subjects with sickle cell anemia received rivaroxaban or placebo. The effect of rivaroxaban on coagulation activation, endothelial activation, inflammation, and microvascular blood flow was evaluated. RESULTS: Fourteen patients (HbSS - 14; females - 9) with mean age of 38 ± 10.6 years were randomized to receive rivaroxaban 20 mg daily or placebo for 4 weeks and, following a 2-week washout phase, were "crossed-over" to the treatment arm opposite to which they were initially assigned. Mean adherence to treatment with rivaroxaban, assessed by pill counts, was 85.6% in the first treatment period and 93.6% in the second period. Treatment with rivaroxaban resulted in a decrease from baseline of thrombin-antithrombin complex versus placebo (-34.4 ug/L [95% CI: -69.4, 0.53] vs. 0.35 ug/L [95% CI: -3.8, 4.5], p = .08), but the difference was not statistically significant. No significant differences were observed in changes from baseline of D-dimer, inflammatory, and endothelial activation markers or measures of microvascular blood flow. Rivaroxaban was well tolerated. CONCLUSIONS: Rivaroxaban was safe but did not significantly decrease coagulation activation, endothelial activation, or inflammation. Rivaroxaban did not improve microvascular blood flow. Adequately powered studies are required to further evaluate the efficacy of rivaroxaban in SCD. Clinicaltrials.gov Identifier: NCT02072668.


Assuntos
Anemia Falciforme/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/uso terapêutico , Adulto , Anemia Falciforme/sangue , Estudos Cross-Over , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Rivaroxabana/efeitos adversos , Resultado do Tratamento
11.
Int J Infect Dis ; 106: 128-133, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33741487

RESUMO

OBJECTIVES: The study aimed to assess COVID-19 impact on the morbidity and mortality of vasooclusive crisis (VOC) in sickle cell anaemia (SCA) patients. METHODS: A prospective cohort study of 100 SCA patients; 50 with COVID-19 (COVID group) and 50 without (non-COVID group). All patients signed written informed consent. RESULTS: The COVID group had a significantly higher VOC episode median per year; 3 (IQR,1-6) vs 2 (IQR,2-12) (P < 0.05). The need for hospitalisation was similar in both groups. The non-COVID group had more history of culture-proven infection (P = 0.05). The COVID-group had more osteonecrosis (P < 0.05), splenic sequestration, splenomegaly and hepatic crisis (P = 0.05, 0.006, 0.02; respectively) and significantly higher (P < 0.05) symptoms of fever, cough, fatigue, abdominal pain and anosmia. Mean haemoglobin, lymphocyte subset, platelets, and reticulocytes were reduced in both groups, while lactate dehydrogenase and ferritin levels were significantly elevated. In the COVID group, the rise in white blood cell count, reticulocyte percentage, platelets and ferritin was subdued (P < 0.05). Two patients in the COVID group and 3 in the non-COVID group died; there was no statistically significant difference in mortality. CONCLUSIONS: Although COVID-19 may have triggered the onset of VOC, it did not significantly influence VOC-related morbidity or mortality in this SCA cohort.


Assuntos
Síndrome Torácica Aguda/sangue , Síndrome Torácica Aguda/epidemiologia , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , COVID-19/sangue , COVID-19/epidemiologia , SARS-CoV-2 , Síndrome Torácica Aguda/mortalidade , Adulto , Anemia Falciforme/mortalidade , COVID-19/mortalidade , Estudos de Coortes , Comorbidade , Feminino , Ferritinas/sangue , Hospitalização , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Contagem de Plaquetas , Estudos Prospectivos , Reticulócitos
12.
Curr Opin Hematol ; 28(3): 164-170, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33631783

RESUMO

PURPOSE OF REVIEW: Small amounts of fetal hemoglobin can be expressed in a subset of adult red blood cells called F-cells. This review examines the potential mechanisms and clinical implications of the heterogeneity of fetal hemoglobin expression. RECENT FINDINGS: Although the heterocellular nature of fetal hemoglobin expression in adult red blood cells has been noted for over 70 years, the molecular basis of this phenomenon has been unclear. Recent discoveries of novel regulators of fetal hemoglobin as well as technological advances have shed new light on these cells. SUMMARY: Fetal hemoglobin reactivation in adult red blood cells through genetic or pharmacological approaches can involve both increasing the number of F-cells and cellular fetal hemoglobin content. New technologies enable the study and eventually the improvement of these parameters in patients with sickle cell disease and ß-thalassemia.


Assuntos
Eritrócitos/metabolismo , Hemoglobina Fetal/biossíntese , Hemoglobina Fetal/genética , Regulação da Expressão Gênica , Heterogeneidade Genética , Adulto , Fatores Etários , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/genética , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , Eritrócitos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Talassemia beta/sangue , Talassemia beta/diagnóstico , Talassemia beta/genética , Talassemia beta/terapia
13.
Curr Opin Hematol ; 28(3): 171-176, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33631786

RESUMO

PURPOSE OF REVIEW: Sickle cell disease (SCD) is a hemolytic anemia caused by a point mutation in the ß globin gene leading to the expression of an abnormal hemoglobin (HbS) that polymerizes under hypoxic conditions driving red cell sickling. Circulating red cells have been extensively characterized in SCD, as their destruction and removal from peripheral blood are the major contributors to anemia. However, few reports showed cellular abnormalities during erythropoiesis in SCD, suggesting that anemia could also be influenced by defects of central origin. RECENT FINDINGS: El Hoss et al. demonstrated ineffective erythropoiesis (IE) in SCD and deciphered the molecular mechanism underlying cell death during the hemoglobin synthesis phase of terminal differentiation. They showed that HbS polymerization induces apoptosis of differentiating erythroblasts and that fetal hemoglobin rescues these cells through its antipolymerization function. SUMMARY: IE is the major cause of anemia in ß-thalassemia patients, and it is generally surmised that it contributes little to anemia of SCD. Recent reports demonstrate the occurrence of IE in SCD patients and show important alterations in the hematopoietic and erythroid niches, both in SCD patients and in the humanized Townes SCD mouse model. This implies that therapeutic strategies initially designed to improve red cell survival in the circulation of SCD patients would also positively impact erythropoiesis and bone marrow cellularity.


Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/etiologia , Eritropoese , Anemia Falciforme/diagnóstico , Anemia Falciforme/terapia , Animais , Apoptose , Microambiente Celular , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Índices de Eritrócitos , Eritrócitos/metabolismo , Eritropoese/genética , Hemoglobina Fetal/química , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , Regulação da Expressão Gênica , Hemoglobinas/genética , Humanos , Mutação , Multimerização Proteica , Globinas beta/genética
15.
PLoS One ; 16(2): e0246067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539452

RESUMO

Priapism is a urologic emergency characterized by an uncontrolled, persistent and painful erection in the absence of sexual stimulation, which can lead to penile fibrosis and impotence. It is highly frequent in sickle cell disease (SCD) associated with hemolytic episodes. Our aim was to investigate molecules that may participate in the regulation of vascular tone. Eighty eight individuals with SCD were included, of whom thirty-seven reported a history of priapism. Priapism was found to be associated with alterations in laboratory biomarkers, as well as lower levels of HbF. Patients with sickle cell anemia using hydroxyurea and those who received blood products seemed to be less affected by priapism. Multivariate analysis suggested that low HbF and NOm were independently associated with priapism. The frequency of polymorphisms in genes NOS3 and EDN1 was not statistically significant between the studied groups, and the presence of the variant allele was not associated with alterations in NOm and ET-1 levels in patients with SCD. The presence of the variant allele in the polymorphisms investigated did not reveal any influence on the occurrence priapism. Future studies involving larger samples, as well as investigations including patients in priapism crisis, could contribute to an enhanced understanding of the development of priapism in SCD.


Assuntos
Anemia Falciforme/complicações , Endotelina-1/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Priapismo/genética , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/genética , Estudos de Casos e Controles , Criança , Endotelina-1/sangue , Hemoglobina Fetal/metabolismo , Estudos de Associação Genética , Humanos , Masculino , Análise Multivariada , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/sangue , Priapismo/sangue , Priapismo/etiologia
17.
Blood Adv ; 5(1): 207-215, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33570644

RESUMO

We aimed to identify predictors of outcomes and survival in patients living in 4 major metropolitan areas who had sickle cell disease (SCD) and COVID-19 to inform best approaches to prevention and care. Data were collected at baseline and during the clinical course in SCD patients diagnosed with COVID-19 in four COVID-19 epicenters. Patients were followed up posthospital discharge for up to 3 months. Of sixty-six SCD patients with COVID-19, fifty patients (75%) required hospitalization, and seven died (10.6%). Patients with preexisting kidney disease (chronic kidney disease) were more likely to be hospitalized. The most common presenting symptom was vaso-occlusive pain. Acute chest syndrome occurred in 30 (60%) of the 50 hospitalized patients and in all who died. Older age and histories of pulmonary hypertension, congestive heart failure, chronic kidney disease, and stroke were more prevalent in patients who died, as were higher creatinine, lactate dehydrogenase, and D-dimer levels. Anticoagulation use while inpatient was twice less common in patients who died. All deaths occurred in individuals not taking hydroxyurea or any other SCD-modifying therapy. Patients with SCD and COVID-19 exhibited a broad range of disease severity. We cannot definitively state that the overall mortality is higher in patients with SCD, although our case fatality rate was ∼10% compared with ∼3% in the general population, despite a median age of 34 years. Individuals with SCD aged >50 years, with preexisting cardiopulmonary, renal disease, and/or stroke not receiving hydroxyurea, who present with high serum creatinine, lactate dehydrogenase, and D-dimer levels, are at higher risk of death, irrespective of genotype or sex.


Assuntos
Anemia Falciforme/complicações , COVID-19/complicações , Síndrome Torácica Aguda/sangue , Síndrome Torácica Aguda/complicações , Síndrome Torácica Aguda/mortalidade , Síndrome Torácica Aguda/terapia , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/mortalidade , Anemia Falciforme/terapia , Antidrepanocíticos/uso terapêutico , COVID-19/sangue , COVID-19/mortalidade , COVID-19/terapia , Progressão da Doença , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Hidroxiureia/uso terapêutico , Masculino , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Adulto Jovem
18.
Am J Hematol ; 96(5): 538-544, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534136

RESUMO

Neurologic complications are common in patients with sickle cell anemia (SCA), but conventional tools such as MRI and transcranial Doppler ultrasonography (TCD) do not fully assess cerebrovascular pathology. Cerebral tissue oximetry measures mixed oxygen saturation in the frontal lobes (SCT O2 ) and provides early prognostic information about tissue at risk of ischemic injury. Untreated patients with SCA have significantly lower SCT O2 than healthy controls that declines with age. Hydroxyurea is effective in preventing many SCA-related complications, but the degree to which it preserves normal neurophysiology is unclear. We analyzed participants enrolled in the Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT02286154), which enrolled participants initiating hydroxyurea using individualized dosing (new cohort) and those previously taking hydroxyurea (old cohort) and was designed to monitor the long-term benefits of hydroxyurea. Cerebral oximetry was performed at baseline and annually. For the new cohort (median starting age = 12 months, n = 55), mean baseline SCT O2 was normal before starting hydroxyurea (mean 65%, 95% CI 58-72%) and significantly increased after 2 years (mean 72%, 95% CI 65-79%, p < .001). The SCT O2 for patients receiving long-term hydroxyurea (median age = 9.6 years) was normal at study entry (mean 66%, 95% CI 58-74%) and remained stable across 2 years. Both cohorts had significantly higher SCT O2 than published data from predominantly untreated SCA patients. Cerebral oximetry is a non-invasive method to assess cerebrovascular pathology that complements conventional imaging. Our results indicate that hydroxyurea suggests protection against neurophysiologic changes seen in untreated SCA.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Hidroxiureia/uso terapêutico , Oximetria/métodos , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , Antidrepanocíticos/administração & dosagem , Antidrepanocíticos/farmacocinética , Antidrepanocíticos/farmacologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Intervenção Médica Precoce , Feminino , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/farmacocinética , Hidroxiureia/farmacologia , Lactente , Masculino , Oximetria/instrumentação , Oxigênio/sangue , Oxiemoglobinas/análise , Medicina de Precisão , Estudos Prospectivos , Adulto Jovem
20.
Ann Hematol ; 100(4): 903-911, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33523291

RESUMO

Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and ßS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and ßS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with ßS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.


Assuntos
Anemia Falciforme/sangue , Bilirrubina/sangue , Colelitíase/etiologia , Doença de Gilbert/sangue , Glucuronosiltransferase/fisiologia , Regiões Promotoras Genéticas/genética , Talassemia alfa/sangue , Adolescente , Adulto , Idoso , Alelos , Anemia Falciforme/complicações , Anemia Falciforme/enzimologia , Anemia Falciforme/genética , Criança , Pré-Escolar , Colelitíase/sangue , Colelitíase/genética , Feminino , Hemoglobina Fetal/análise , Genótipo , Doença de Gilbert/enzimologia , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Haplótipos/genética , Hemólise , Humanos , Hiperbilirrubinemia/enzimologia , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Talassemia alfa/complicações , Talassemia alfa/enzimologia , Talassemia alfa/genética
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