RESUMEN
BACKGROUND: Suboptimal medication adherence is common across youth with chronic health conditions and may contribute to health disparities and adverse health outcomes, especially in underserved communities. METHODS: Using pharmacy prescription records and guided by the World Health Organization Multidimensional Adherence Model, we examined patient-, treatment-, and health system-related factors that may affect hydroxyurea adherence in 72 youth with sickle cell disease (SCD), 10-18 years who had participated in the multisite "Hydroxyurea Adherence for Personal Best in SCD" (HABIT) feasibility (6 months) and efficacy (12 months) trials. Pharmacy data were collected from the year prior to study entry through the duration of each trial. We also examined hydroxyurea dose at baseline, prescribing patterns (hydroxyurea formulation and dose prescribed), quantity of hydroxyurea dispensed, and number of daily capsules/tablets prescribed. Data were analyzed using descriptive statistics. RESULTS: On average, youth were prescribed 1095 ± 402 mg hydroxyurea per day, requiring ingestion of 3 or more capsules for 39.4% of youth. Frequently identified potential barriers were complex medication regimens in which dose of hydroxyurea differed by day of week (47.2%); receipt of an inadequate (< 30 days) supply of hydroxyurea from the pharmacy ≥ 3 times during record collection period (29.2%); and prescription of hydroxyurea suspension suggesting problems swallowing capsules (22.2%). In this sample, most youth were exclusively prescribed 500 mg capsules (62.5%), which was associated with complex medication regimens (RR 3.0, 95% CI 1.4-6.7). Potential barriers were common, occurred at all levels and are potentially modifiable with targeted interventions at the treatment- and health system-related levels.
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Anemia de Células Falciformes , Antidrepanocíticos , Hidroxiurea , Cumplimiento de la Medicación , Humanos , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Anemia de Células Falciformes/tratamiento farmacológico , Adolescente , Masculino , Niño , Femenino , Cumplimiento de la Medicación/estadística & datos numéricos , Antidrepanocíticos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricosRESUMEN
Sickle cell disease (SCD) is a group of complex genetic disorders of hemoglobin with multisystem manifestations. The scope of this clinical report is such that in-depth recommendations for management of all complications is not possible. Rather, the authors present an overview focused on the practical management of children and adolescents with SCD and the complications that are of particular relevance to pediatric primary care providers. References with detailed commentary provide further information. Timely and appropriate treatment of acute illness is critical, because life-threatening complications may develop rapidly. Specialized comprehensive medical care decreases morbidity and mortality during childhood. The provision of comprehensive care is a time-intensive endeavor that includes ongoing patient and family education, periodic comprehensive evaluations and other disease-specific health maintenance services, nursing support, psychosocial care, and genetic counseling. Ideally, this care includes comanagement by the pediatrician or other pediatric primary care provider and a team of specialist SCD experts: Hematologist, other pediatric specialists, advanced practice providers, nurse specialists, social workers, patient navigators, and educational liaisons.
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Anemia de Células Falciformes , Humanos , Anemia de Células Falciformes/terapia , Niño , Adolescente , Atención Primaria de SaludRESUMEN
BACKGROUND: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years. METHODS: In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sß zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing. FINDINGS: We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 109 cells per L to 3·6 [2·2] × 109 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths. INTERPRETATION: Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa. FUNDING: US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation.
Asunto(s)
Anemia de Células Falciformes , Antidrepanocíticos , Hidroxiurea , Humanos , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/sangre , Preescolar , Niño , Masculino , Femenino , África del Sur del Sahara , Estudios de Seguimiento , Lactante , Antidrepanocíticos/uso terapéutico , Antidrepanocíticos/efectos adversos , Antidrepanocíticos/administración & dosificación , Resultado del Tratamiento , Relación Dosis-Respuesta a DrogaRESUMEN
Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two-month pre-treatment screening period followed by 6 months of fixed-dose hydroxyurea (15-20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person-years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person-years was 43.2 before hydroxyurea, 21.7 on fixed-dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre-treatment (IRR 0.25, 95% confidence interval [CI] 0.18-0.35, p < .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39-0.63, p < .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub-Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply.
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Anemia de Células Falciformes , Hidroxiurea , Niño , Humanos , Hidroxiurea/uso terapéutico , Antidrepanocíticos/uso terapéutico , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Uganda , KeniaRESUMEN
Despite disease-modifying effects of hydroxyurea on sickle cell disease (SCD), poor adherence among affected youth commonly impedes treatment impact. Following our prior feasibility trial, the "Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT)" multi-site randomized controlled efficacy trial aimed to increase hydroxyurea adherence for youth with SCD ages 10-18 years. Impaired adherence was identified primarily through flagging hydroxyurea-induced fetal hemoglobin (HbF) levels compared to prior highest treatment-related HbF. Eligible youth were enrolled as dyads with their primary caregivers for the 1-year trial. This novel semi-structured supportive, multidimensional dyad intervention led by community health workers (CHW), was augmented by daily tailored text message reminders, compared to standard care during a 6-month intervention phase, followed by a 6-month sustainability phase. Primary outcomes from the intervention phase were improved Month 6 HbF levels compared to enrollment and proportion of days covered (PDC) for hydroxyurea versus pre-trial year. The secondary outcome was sustainability of changes up to Month 12. The 2020-2021 peak coronavirus disease 2019 (COVID-19) pandemic disrupted enrollment and clinic-based procedures; CHW in-person visits shifted to virtual scheduled interactions. We enrolled 50 dyads, missing target enrollment. Compared to enrollment levels, both HbF level and PDC significantly - but not sustainably - improved within the intervention group (p = .03 and .01, respectively) with parallel increased mean corpuscular volume (MCV) (p = .05), but not within controls. No significant between-group differences were found at Months 6 or 12. These findings suggest that our community-based, multimodal support for youth-caregiver dyads had temporarily improved hydroxyurea usage. Durability of impact should be tested in a trial with longer duration of CHW-led and mobile health support.
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Anemia de Células Falciformes , Hidroxiurea , Adolescente , Humanos , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Agentes Comunitarios de Salud , Hemoglobina Fetal/análisis , Hábitos , Hidroxiurea/uso terapéutico , Cumplimiento de la Medicación , Niño , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.
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Anemia de Células Falciformes , Enfermedades Vasculares , Ratones , Animales , Hemólisis , Monocitos/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Factor Estimulante de Colonias de Macrófagos/uso terapéutico , Células Endoteliales/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/tratamiento farmacológico , Enfermedades Vasculares/metabolismo , Diferenciación Celular , Selectinas/metabolismo , Selectinas/uso terapéuticoRESUMEN
Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include â¼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.
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Anemia de Células Falciformes , Malaria , Humanos , Niño , Hidroxiurea/efectos adversos , Incidencia , Esplenomegalia/epidemiología , Esplenomegalia/tratamiento farmacológico , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/epidemiología , Malaria/tratamiento farmacológico , Malaria/epidemiología , Malaria/prevención & control , África del Sur del Sahara/epidemiologíaRESUMEN
Youth with sickle cell disease (SCD) and their caregivers are susceptible to stress and depression, perhaps exacerbated by pandemic-associated health and economic concerns. Most of the 50 youth-caregiver dyads enrolled in the multisite trial, Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT), took an online survey of self-reported mental health symptoms and food insecurity during the 2020 COVID-19 pandemic. Compared to largely pre-pandemic results, prevalence of mental health symptoms in dyad members appeared to have shifted: fewer youth and more caregivers were affected during the pandemic; many of both groups lacked optimism. Pandemic/post-pandemic screening of youth with SCD for mental health symptoms and food insecurity appears warranted.
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Anemia de Células Falciformes , COVID-19 , Adolescente , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/psicología , COVID-19/epidemiología , Cuidadores/psicología , Depresión/epidemiología , Depresión/etiología , Depresión/psicología , Humanos , Salud Mental , PandemiasRESUMEN
This retrospective study investigates the relationship between the presence of a documented viral infection in children with sickle cell disease during their first splenic sequestration crisis and their odds of recurrence. Forty-eight children were admitted to our hospital between 2008 and 2018 with a splenic sequestration crisis. Thirty-six had respiratory viral panels done on admission, 13 of whom were positive. Two additional children were diagnosed with parvovirus B19 infection by serology. The recurrence rate was 52% (17/33) for those deemed negative for viral illness compared with 33% (5/15) among those with a positive documented viral illness, which was not statistically different (P=0.35). HbSC genotype decreased, and reticulocytosis increased the odds of recurrence. Further research is needed to substantiate these findings.
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Anemia de Células Falciformes , Eritema Infeccioso , Infecciones por Parvoviridae , Parvovirus B19 Humano , Anemia de Células Falciformes/genética , Niño , Genotipo , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Sickle cell disease is characterized by the painful recurrence of vaso-occlusive events. Gene therapy with the use of LentiGlobin for sickle cell disease (bb1111; lovotibeglogene autotemcel) consists of autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified ß-globin gene, which produces an antisickling hemoglobin, HbAT87Q. METHODS: In this ongoing phase 1-2 study, we optimized the treatment process in the initial 7 patients in Group A and 2 patients in Group B with sickle cell disease. Group C was established for the pivotal evaluation of LentiGlobin for sickle cell disease, and we adopted a more stringent inclusion criterion that required a minimum of four severe vaso-occlusive events in the 24 months before enrollment. In this unprespecified interim analysis, we evaluated the safety and efficacy of LentiGlobin in 35 patients enrolled in Group C. Included in this analysis was the number of severe vaso-occlusive events after LentiGlobin infusion among patients with at least four vaso-occlusive events in the 24 months before enrollment and with at least 6 months of follow-up. RESULTS: As of February 2021, cell collection had been initiated in 43 patients in Group C; 35 received a LentiGlobin infusion, with a median follow-up of 17.3 months (range, 3.7 to 37.6). Engraftment occurred in all 35 patients. The median total hemoglobin level increased from 8.5 g per deciliter at baseline to 11 g or more per deciliter from 6 months through 36 months after infusion. HbAT87Q contributed at least 40% of total hemoglobin and was distributed across a mean (±SD) of 85±8% of red cells. Hemolysis markers were reduced. Among the 25 patients who could be evaluated, all had resolution of severe vaso-occlusive events, as compared with a median of 3.5 events per year (range, 2.0 to 13.5) in the 24 months before enrollment. Three patients had a nonserious adverse event related or possibly related to LentiGlobin that resolved within 1 week after onset. No cases of hematologic cancer were observed during up to 37.6 months of follow-up. CONCLUSIONS: One-time treatment with LentiGlobin resulted in sustained production of HbAT87Q in most red cells, leading to reduced hemolysis and complete resolution of severe vaso-occlusive events. (Funded by Bluebird Bio; HGB-206 ClinicalTrials.gov number, NCT02140554.).
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Anemia de Células Falciformes/terapia , Terapia Genética , Vectores Genéticos , Trasplante de Células Madre Hematopoyéticas , Hemoglobinas/genética , Lentivirus , Trasplante de Células Madre , Globinas beta/genética , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Niño , Femenino , Hemoglobina Fetal , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Grado de Desobstrucción Vascular , Adulto JovenRESUMEN
Cardiac abnormalities such as left ventricular hypertrophy, left ventricular dilation, and pulmonary hypertension in sickle cell anemia have been previously described. Hydroxyurea, a disease-modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia receiving hydroxyurea therapy is lacking. The goal of this retrospective study was to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children's Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were being treated with hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for <1 year; these patients had a significantly greater prevalence of left ventricular dilation compared with those who had been on treatment for >1 year. Serial echocardiograms of patients receiving hydroxyurea were then analyzed. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. In addition, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow up this patient cohort for a longer duration.
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Anemia de Células Falciformes , Hidroxiurea , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Niño , Estudios de Cohortes , Ecocardiografía , Humanos , Hidroxiurea/uso terapéutico , Estudios RetrospectivosRESUMEN
We previously found that neurodevelopmental deficits commonly occurred in three-year-olds with sickle cell disease (SCD), but clinical significance was uncertain because a comparison group was lacking. Our objective in the current study was to prospectively compare neurodevelopment in three-year-old children with SCD to an age-appropriate control group. The Brigance Preschool Screen II is a neurodevelopmental screening examination which can be administered in 15-20 min. SCD patients (Group 1) were compared with community controls of similar age and ethnicity enrolled in daycare/preschool (Group 2). SCD patients who were receiving hydroxycarbamide treatment were also compared (Group 3). Two hundred forty-five three-year-olds were evaluated: Group 1, 111; Group 2, 114; and Group 3, 20. The below cut-off rate on the Brigance test was higher in Group 1 (73%) than in Group 2 (61%; P = 0·04). In multivariate analysis of Group 1 patients, only lower household income and more persons living in the home were independent predictors of this. Patients with SCD and matched controls had high rates of 'failing' the Brigance test. The below cut-off rate in untreated children with SCD was associated with low household income and increased number of persons living in the home.
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Anemia de Células Falciformes/complicaciones , Tamizaje Masivo , Trastornos del Neurodesarrollo/etiología , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/epidemiología , Antidrepanocíticos/uso terapéutico , Preescolar , Composición Familiar , Femenino , Humanos , Hidroxiurea/uso terapéutico , Renta , Masculino , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/epidemiología , Pruebas Neuropsicológicas , Estudios Prospectivos , Determinantes Sociales de la SaludRESUMEN
BACKGROUND: Adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had high rates of thrombosis. A novel condition in children infected with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), has limited data on their prothrombotic state or need for thromboprophylaxis. OBJECTIVES: We aimed to analyze the prothrombotic state using coagulation profiles, rotational thromboelastometry (ROTEM) parameters and clinical outcomes, to determine if this could aid in risk stratification for thromboprophylaxis. METHODS: This analysis included patients (<21 years of age) with a diagnosis of MIS-C (n = 40) and controls (presenting with suspicion of MIS-C but later ruled out; n = 26). RESULTS: MIS-C patients had higher levels of inflammatory markers including D-dimer (p < .0001), compared with controls, along with evidence of hypercoagulability on ROTEM with elevated evaluation of fibrinogen activity (FIBTEM) maximum clot firmness (MCF) (p < .05). For MIS-C patients with D-dimers >1000 ng/ml, there was a significant correlation of FIBTEM MCF (p < .0001) with a mean value of 37.4 (standard deviation 5.1). D-dimer >2144 ng/ml was predictive of intensive care unit admission (area under the curve [AUC] 0.80; 95% confidence interval, 0.60-0.99; p < .01; sensitivity: 82%, specificity: 75%), and elevated FIBTEM MCF (AUC 1 for >2500 ng/ml). MIS-C patients (50%) received enoxaparin thromboprophylaxis (in addition to aspirin) with significant improvement in their inflammatory and ROTEM parameters upon outpatient follow-up; none developed symptomatic thrombosis. CONCLUSIONS: Despite an observed prothrombotic state, none of the MIS-C patients (on aspirin alone or in combination with enoxaparin) developed symptomatic thrombosis. ROTEM, in addition to coagulation profiles, may be helpful to tailor thromboprophylaxis in critically ill MIS-C patients.
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COVID-19 , Tromboembolia Venosa , Adulto , Anticoagulantes , Niño , Humanos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , TromboelastografíaAsunto(s)
Antiinflamatorios/uso terapéutico , COVID-19/complicaciones , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Proteínas Qa-SNARE/genética , Antiinflamatorios/administración & dosificación , Preescolar , Mutación del Sistema de Lectura , Homocigoto , Humanos , Proteína Antagonista del Receptor de Interleucina 1/administración & dosificación , Linfohistiocitosis Hemofagocítica/genética , Masculino , SARS-CoV-2/aislamiento & purificación , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: The Spectra Optia allows automated performance of red blood cell reduction and isovolemic hemodilution (IHD) prior to standard red cell exchange (RCE), and is primarily intended for patients with sickle cell disease (SCD) undergoing chronic RCE. Data on the safety of inducing transient further anemia and the benefits of IHD-RCE is limited and occasionally contradictory. STUDY DESIGN AND METHODS: In this retrospective crossover analysis of six patients with SCD who underwent chronic exchange with standard RCE (Cobe Spectra) followed by IHD-RCE (Spectra Optia), we compared safety and benefit outcomes with IHD-RCE vs standard RCE. RESULTS: There were statistically but not clinically significant drops in blood pressure in the post-IHD phase. With IHD-RCE, there were significant reductions in red blood cell (RBC) usage and/or lower fraction of cells and significant increases in postprocedure hematocrit (Hct) associated with increased preprocedure Hct. There were no differences achieved in the time interval between procedures or in the net RBC gain with IHD-RCE. Overall, there were also no significant differences in pre- and postprocedure percentage of hemoglobin S, reticulocyte count, interval daily hemoglobin A decrement, or postprocedure white blood cell, neutrophil, or platelet counts. CONCLUSIONS: Our study supports that IHD-RCE can be safely used in patients with stroke risk and compared to standard RCE, results in benefits of lower RBC usage and/or fraction of cells remaining and higher postprocedure Hct associated with higher preprocedure Hct. These findings support wider use of IHD-RCE, especially in the current environment with reduced availability of minority units.
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Anemia de Células Falciformes/terapia , Eliminación de Componentes Sanguíneos/métodos , Transfusión Sanguínea/métodos , Separación Celular/métodos , Eritrocitos , Adolescente , Anemia de Células Falciformes/sangre , Automatización , Recuento de Células Sanguíneas , Conservación de la Sangre , Niño , Transfusión de Eritrocitos , Femenino , Humanos , Masculino , Seguridad del PacienteRESUMEN
Patients with sickle cell disease (SCD) are living longer and subsequently more apt to develop cardiopulmonary dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels have been used in adults with SCD to assess for pulmonary hypertension and mortality. While the incidence of PH is low in pediatrics, it is reasonable to presume that NT-proBNP levels can be used to assess risk for the development of cardiopulmonary morbidity. We hypothesized that NT-proBNP levels would be increased in patients with SCD compared to age-adjusted healthy children; additionally, these levels would be associated with labs indicative of hemolysis and would demonstrate evidence of obstructive lung disease and cardiac dysfunction. We retrospectively evaluated patients with SCD, 8-18 years old, at a large, tertiary care children's hospital. NT-proBNP levels were assessed in correlation with hemolytic lab work, spirometry, and echocardiographic data. The age group 8-14 years old, 75% of our cohort's population, had a median NT-proBNP of 70 pg/ml, greater than their age-adjusted counterparts (52 pg/ml). NT-proBNP levels were associated with an increased degree of hemolysis when compared with hemoglobin (Hb) (r = -0.43, p < .0001), reticulocyte count (r = .25, p = .01) and lactate dehydrogenase levels (r = .47, p < .0001). An inverse trend was found between NT-proBNP and spirometric data. Finally, a positive correlation was found between NT-proBNP and diastolic left ventricular size (r = .28, p = .047]. The correlations found suggest that NT-proBNP may be used prospectively to identify patients with SCD at increased risk for the development of cardiopulmonary dysfunction.
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Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/fisiopatología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Adolescente , Biomarcadores/sangre , Niño , Ecocardiografía , Femenino , Hemólisis , Humanos , Masculino , Pruebas de Función Respiratoria , Estudios RetrospectivosRESUMEN
The coagulopathy of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well documented in adults, with increases in D-dimer and prothrombin time found to be strong predictors of mortality, and anticoagulation shown to decrease this mortality. Viscoelastic parameters such as elevations in maximum clot firmness (MCF) on rotational thromboelastometry (ROTEM) have correlated with a hypercoagulable state in adults with SARS-CoV-2. We report our experience in children infected with SARS-CoV-2, with noted elevations in D-dimer and MCF on ROTEM (indicating hypercoagulability). Exploration of viscoelastic testing to provide additional laboratory-based evidence for pediatric-specific risk assessment for thromboprophylaxis in SARS-CoV-2 is warranted.
Asunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Síndrome Respiratorio Agudo Grave , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Trombosis , Tromboembolia Venosa , Adulto , Anticoagulantes , Betacoronavirus , COVID-19 , Niño , Humanos , SARS-CoV-2Asunto(s)
Anemia de Células Falciformes , COVID-19 , SARS-CoV-2 , Adolescente , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/mortalidad , Anemia de Células Falciformes/terapia , COVID-19/etiología , COVID-19/mortalidad , COVID-19/terapia , Preescolar , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Children with sickle cell disease (SCD) are at risk for neurocognitive deficits, which can lead to effects on academic performance and later job attainment. However, screening in children at high risk for poor academic performance (PAP) in a clinic setting has been limited. The goal was to identify young children with SCD at high risk for PAP via administration of a standardized screening tool at the clinic visit. PROCEDURE: Parents of 20 patients were asked to complete the Behavior Assessment System for Children, 3rd edition (BASC-3) Parent Rating Scale. Children ages six to nine years and all SCD genotypes were included. Those patients who scored at least 1 standard deviation below the mean were considered high risk. Statistics was used to associate demographic, academic, and laboratory data with risk status (RS). RESULTS: Four of 20 patients (20%) were found to be at risk by the BASC-3. A significant association was found between those with a history of PAP and RS (P = 0.001). A trend toward association was found between baseline hemoglobin, reticulocyte count, and RS. Children not at risk had a higher hemoglobin level and lower reticulocyte count (P = 0.37 and P = 0.20, respectively). Those on hydroxyurea were significantly less likely to score as at risk (P = 0.014), whereas those with siblings may be at greater risk (P = 0.037). CONCLUSION(S): A parent-directed screening tool may identify children with SCD in need of additional school support. Further prospective studies are necessary to understand correlations found between hemoglobin, reticulocyte count, and hydroxyurea treatment and risk for PAP.