RESUMEN
Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.
Asunto(s)
Anemia de Células Falciformes , Sobrecarga de Hierro , Talasemia , Adolescente , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Transfusión Sanguínea , Deferiprona/uso terapéutico , Deferoxamina/efectos adversos , Femenino , Humanos , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Masculino , Piridonas/efectos adversos , Talasemia/complicaciones , Talasemia/tratamiento farmacológico , TransferasasRESUMEN
BACKGROUND: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. OBJECTIVE: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. METHODS: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. RESULTS: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. CONCLUSIONS: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.
Asunto(s)
Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Tipificación y Pruebas Cruzadas Sanguíneas , Medicina Basada en la Evidencia , Humanos , Sobrecarga de Hierro/prevención & control , Sobrecarga de Hierro/terapia , Reacción a la Transfusión/prevención & control , Reacción a la Transfusión/terapiaRESUMEN
Chronic transfusion therapy has played a central role in extending life expectancy for patients with hemoglobinopathies such as thalassemia. However, this life-saving therapy is associated with numerous complications that now comprise the bulk of management considerations for patients with thalassemia. This review reports on the experience of the Thalassemia Longitudinal Cohort and reviews available literature to establish guidelines for the management of patients with thalassemia.
Asunto(s)
Hemoglobinopatías/terapia , Monitoreo Fisiológico/normas , Talasemia/terapia , Transfusión Sanguínea , Humanos , Estudios LongitudinalesRESUMEN
OBJECTIVE: To assess the rates and types of complications associated with deep sedation in children with sickle cell disease (SCD) and to explore potential risk factors. STUDY DESIGN: This was a retrospective cohort study of children with SCD and a comparison group of children without SCD who underwent magnetic resonance imaging with deep sedation. The rates of general and SCD-associated sedation complications were calculated, and potential associated clinical and laboratory variables were assessed. RESULTS: A total of 162 sedation records in 94 subjects with SCD and 324 sedation records in 321 subjects without SCD were assessed (mean age, 4.3 years in both groups). Pentobarbital, fentanyl, and midazolam were used in the majority of sedation episodes without routine presedation transfusion. Sedation-related complication rates did not differ significantly between the SCD and comparison groups. Within 1 month after the sedation procedure, 17 children (10%) experienced a vaso-occlusive pain episode (VOE), and 2 children (1.2%) developed acute chest syndrome. Preprocedure and postprocedure rates of these complications did not differ significantly. Subjects who developed VOE after sedation had a significantly higher VOE rate before sedation, but no other significant clinical or laboratory risk factors were identified. CONCLUSION: Deep sedation in young children with SCD using a standard protocol is safe, with a sedation-related complication rate comparable to that of the general pediatric population. The observed rate of VOE, although not significantly higher than expected, warrants further investigation.
Asunto(s)
Síndrome Torácico Agudo/etiología , Anemia de Células Falciformes/fisiopatología , Sedación Profunda/métodos , Dolor/etiología , Adyuvantes Anestésicos/efectos adversos , Anemia de Células Falciformes/complicaciones , Niño , Preescolar , Sedación Profunda/efectos adversos , Femenino , Fentanilo/efectos adversos , Humanos , Imagen por Resonancia Magnética , Masculino , Midazolam/efectos adversos , Seguridad del Paciente , Pentobarbital/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts. STUDY DESIGN: In this cross-sectional study, we evaluated the health history, laboratory values, and brain magnetic resonance imaging findings of participants with sickle cell disease (hemoglobinSS or hemoglobinSß°-thalassemia) with no history of overt stroke or seizures. Participants characterized headache severity and quality. Migraine was defined by International Headache Society criteria modified for increased sensitivity in children. Neuroradiology and neurology committees adjudicated the presence of silent cerebral infarction by review of magnetic resonance imaging and standardized examination by pediatric neurologists. RESULTS: The cohort included 872 children (51.1% males), ranging in age from 5 to 15 years (mean age, 9.1 years). Of these children, 317 (36.4%) reported recurrent headaches, and 132 (15.1%) reported migraines. In multivariable logistic regression analyses, both were associated with lower steady-state hemoglobin (P = .01 for headaches; P < .01 for migraines) and higher pain rate (P < .01 for headaches; P < .01 for migraines), defined as the number of admissions requiring opioids in the previous 3 years. The presence of silent cerebral infarction was not associated with recurrent headaches or migraines. Only 1.9% (6 of 317) of children with recurrent headaches received medication for headache prophylaxis. CONCLUSION: Recurrent headaches and migraines are common and undertreated in children with sickle cell disease. Low hemoglobin levels and high pain rates are associated with recurrent headaches and migraines; whereas, silent cerebral infarction is not.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Infarto Cerebral/etiología , Cefalea/etiología , Hemoglobinas/metabolismo , Trastornos Migrañosos/etiología , Adolescente , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/terapia , Biomarcadores/sangre , Transfusión Sanguínea , Infarto Cerebral/diagnóstico , Infarto Cerebral/prevención & control , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Dolor/etiología , Recurrencia , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To determine the frequency of acute care visits and risk factors for central nervous system (CNS) events in children with homozygous sickle cell disease (SCD-SS) with an acute headache. STUDY DESIGN: This is a retrospective cohort study of acute care visits for headache in children with SCD-SS. The prevalence of headache visits, neuroimaging evaluation, and acute CNS events were calculated and clinical and laboratory variables assessed. RESULTS: Headache was the chief complaint in 102 of 2685 acute care visits (3.8%) by children with SCD-SS. Acute CNS events were detected in 6.9% of these visits. Neuroimaging was performed in 42.2% of visits, and acute CNS events were identified in 16.3% of studies. Factors associated with acute CNS events included older age, history of stroke, transient ischemic attack, or seizure, neurologic symptoms, focal neurologic exam findings, and elevated platelets. CONCLUSIONS: Acute headache is common in pediatric SCD-SS and more frequently associated with acute CNS events than in the general pediatric population. A history of stroke, transient ischemic attack, seizures, neurologic symptoms, focal neurologic exam, or elevated platelet counts at presentation warrant confirmatory imaging studies. Whether a more limited workup is adequate for other children should be confirmed in a larger, prospective study.
Asunto(s)
Anemia de Células Falciformes/epidemiología , Cefalea/epidemiología , Adolescente , Factores de Edad , Encéfalo/patología , Niño , Preescolar , Estudios de Cohortes , Servicio de Urgencia en Hospital , Femenino , Humanos , Ataque Isquémico Transitorio/epidemiología , Recuento de Leucocitos , Imagen por Resonancia Magnética , Masculino , Examen Neurológico , Recuento de Plaquetas , Estudios Retrospectivos , Convulsiones/epidemiología , Accidente Cerebrovascular/epidemiología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
OBJECTIVE: To measure body composition in patients with thalassemia and explore its relationship to abnormal growth and bone mass. STUDY DESIGN: We conducted a cross-sectional, multicenter study. Fat, lean, and bone mineral density (BMD) were assessed with dual-energy x-ray absorptiometry. Medical history, food frequency, and physical activity questionnaires were conducted in 257 transfused patients with thalassemia (age, 23.7+/-11 years [mean+/-SD]; 51% male) compared with 113 non-transfused patients (21.3+/-13 years; 44% male). RESULTS: Subjects with thalassemia were leaner compared with healthy American subjects from National Health and Nutrition Examination Survey III data. Transfused subjects had a higher percentage of body fat compared with non-transfused subjects after controlling for age, sex, and ethnicity; 11.8% of non-transfused pediatric subjects were considered underweight, significantly lower than National Health and Nutrition Examination Survey data (P=.03). Hemoglobin level was positively related to lean mass (P=.008). Body fat and lean mass were positive predictors for both height and BMD z-scores after adjustment for transfusion status, age, sex, ethnicity, calcium intake, and physical activity (all P<.001). CONCLUSION: Although most adult patients with thalassemia had healthy body composition with rare obesity, young non-transfused patients appear at risk for being underweight. Optimizing physical activity and appropriate use of transfusion therapy may improve growth and bone health in these patients who are at-risk for being underweight.
Asunto(s)
Transfusión Sanguínea/estadística & datos numéricos , Composición Corporal , Estatura , Densidad Ósea , Talasemia/epidemiología , Adolescente , Adulto , Factores de Edad , Calcio de la Dieta/uso terapéutico , Niño , Comorbilidad , Estudios Transversales , Femenino , Estado de Salud , Humanos , Hipogonadismo/epidemiología , Hierro/metabolismo , Masculino , Persona de Mediana Edad , Factores Sexuales , Talasemia/metabolismo , Factores de Tiempo , Vitamina D/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: To assess the impact of our transcranial Doppler ultrasonography (TCD) program on the incidence of first stroke and the rate of transfusion for stroke prevention in children with sickle cell disease. STUDY DESIGN: In this single-institution, retrospective study, we compared the incidence of stroke and of transfusion for stroke prevention in 475 patients observed in the 8-year period before instituting TCD screening with the rate in 530 children in the 8-year period after. RESULTS: The incidence of overt stroke in the pre-TCD period was 0.67 per 100 patient-years, compared with 0.06 per 100 patient-years in the post-TCD period (P<.0001). Of the 2 strokes in the post-TCD period, 1 occurred in a child too young for the screening protocol, and 1 occurred in a child with high velocities solely in the anterior cerebral arteries. The rate of transfusion therapy for stroke prevention increased from 0.67 per 100 patient-years to 1.12 per 100 patient-years since instituting our program (P=.008). CONCLUSIONS: Our program has been successful in reducing the rate of first overt stroke, but with increased use of transfusion. Additional modifications to screening might further reduce the risk of first stroke, and studies of alternative treatments may be beneficial.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Transfusión Sanguínea , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/prevención & control , Ultrasonografía Doppler Transcraneal , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: To compare the prevalence of frequent headache in children with sickle cell disease (SCD) to that of black control subjects and to assess factors associated with headache in SCD. STUDY DESIGN: In this cross-sectional study, a headache questionnaire was administered to subjects with SCD and black control subjects. Subjects answered supplementary questions about SCD complications. Clinical and radiographic information were abstracted from medical charts for subjects with SCD. RESULTS: Children (n = 241) with SCD and 141 control subjects were studied; 32.4% (95% CI 26.5%-38.7%) of subjects with SCD reported having headaches at least weekly, similar to control subjects at 27% (95% CI 19.8%-35.1%, P = NS); however, in children <13 years, headache was more common in subjects with SCD than in control subjects (24% vs 9.7%, P = .013). The prevalence of headache was similar among the different SCD genotypes. Factors associated with frequent headaches in subjects with SCD included older age, frequent vaso-occlusive pain episodes, symptoms of obstructive sleep apnea, and cerebral vessel stenosis detected by magnetic resonance angiography. CONCLUSION: The prevalence of headaches in children with SCD is similar to the general population; however, younger children with SCD report headaches more frequently than control subjects. The cause of headache is likely multifactorial, and SCD-specific factors may contribute.