RESUMO
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.
Assuntos
Anemia Falciforme , Sobrecarga de Ferro , Talassemia , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Transfusão de Sangue , Deferiprona/uso terapêutico , Desferroxamina/efeitos adversos , Feminino , Humanos , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Masculino , Piridonas/efeitos adversos , Talassemia/complicações , Talassemia/tratamento farmacológico , TransferasesRESUMO
OBJECTIVES: To determine the applicability of the 4Ts score and the Heparin-Induced Thrombocytopenia (HIT) Expert Probability (HEP) score in children with suspected HIT and to estimate the number of children potentially at risk of HIT. STUDY DESIGN: We retrospectively estimated 4Ts and HEP scores in a cohort of 50 children referred for laboratory screening with enzyme immunoassay. In addition, minor modifications were introduced to the 4Ts score (modified 4Ts score) to adapt it for use in the pediatric setting. All patients with positive enzyme immunoassays were tested with serotonin release assay. We also extracted the number of patients started on heparins in a similar period of time. RESULTS: The median age at the time of testing was 4 years (25th-75th percentile, 8.7 months to 13.5 years); 78% of patients had low and 22% had intermediate risk pretest probability scores using the original 4Ts score; 86% had low risk and 14% had intermediate risk scores using the modified 4Ts score; 54% of children had a HEP score of ≥2. Six patients (12%) had a positive (≥0.40 optical density units) enzyme immunoassay, but none had a positive serotonin release assay. Based on anticoagulation dose, there were 1-2 new daily potentially high-risk exposures to heparinoids at our institution. CONCLUSIONS: The modified 4Ts and original 4Ts scores may be more adequate than the HEP score to determine HIT pretest probability in children. Despite the number of patients potentially at risk, HIT is rare in pediatrics.
Assuntos
Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: To assess the validity of existing clinical scales assessing the presence of physical and functional abnormalities for diagnosing post-thrombotic syndrome (PTS) in children, including specific evaluation of use in children with congenital heart disease (CHD). STUDY DESIGN: One hundred children aged >2 years (average age, 6 years), including 33 with CHD and previously proven extremity deep vein thrombosis (DVT), 37 with CHD and no previous DVT, and 30 healthy siblings, were blindly assessed for PTS using the modified Villalta Scale (MVS). All patients aged <6 years underwent neurodevelopmental testing and an age-appropriate quality of life assessment. RESULTS: The MVS identified mild PTS in 20 children and moderate PTS in 1 child (including 14 of 33 [42%] in the CHD/DVT group, 5 of 37 [14%] in the CHD/no DVT group, and 2 of 30 controls [7%]). The diagnosis of PTS was confirmed clinically in 14 patients, all of whom had previous thrombosis and 1 of whom was MVS-negative. MVS had an accuracy of 91% and performed reasonably well as a screening tool but poorly as a diagnostic tool. MVS reliability was acceptable. Children with PTS had similar quality of life as those without PTS but had higher rates of neurodevelopmental delays in gross motor skills (70% vs 24%; P = .02) and problem-solving indicators (60% vs 15%; P = .008). CONCLUSIONS: Using the MVS scale for PTS screening in children with CHD is feasible and reliable, and the scale has good correlation with a clinical diagnosis of PTS despite a high prevalence of false-positive findings. Further research is needed to determine the clinical relevance of PTS in this population.
Assuntos
Transtornos do Neurodesenvolvimento/etiologia , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/etiologia , Qualidade de Vida , Trombose Venosa/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Pós-Trombótica/fisiopatologia , Valor Preditivo dos Testes , Trombose Venosa/fisiopatologiaRESUMO
OBJECTIVES: To evaluate management and outcomes of thrombosis after pediatric cardiac surgery and stratify thrombi according to risk of short- and long-term complications to better guide therapeutic choices. STUDY DESIGN: Retrospective review was performed of 513 thrombi (400 occlusive) diagnosed after 213 pediatric cardiac operations. Long-term outcomes over time were assessed with the use of parametric hazard regression models. RESULTS: Serious complications and/or high-intensity treatment occurred with 17%-24% of thrombi depending on location, most commonly in thrombi affecting the cardiac and cerebral circulation. Bleeding complications affected 13% of patients; associated factors included thrombolytics (OR 8.7, P < .001), greater daily dose of unfractionated heparin (OR 1.25 per 5 U/kg/day, P = .03), and extracorporeal support (OR 4.5, P = .007). Radiologic thrombus persistence was identified in 30% ± 3% at 12 months; associated factors included extracorporeal support (hazard ratio [HR] 1.9, P = .003), venous (HR 1.7, P = .003), and occlusive thrombi at presentation (HR 1.8, P = .001); greater oxygen saturation before surgery (HR 1.13/10%, P = .05) and thrombi in femoral veins (HR 1.9, P = .001) were associated with increased hazard of resolution. Freedom from postthrombotic syndrome was 83% ± 4% at 6 years, greater number of persistent vessel segment occlusions (HR 1.8/vessel, P = .001) and greater fibrinogen at diagnosis (HR 1.1 per g/L, P = .02) were associated with increased hazard. CONCLUSIONS: Thrombosis outcomes after pediatric cardiac surgery remain suboptimal. Given that more intensive treatment would likely increase the risk of bleeding, the focus should be on both thrombosis-prevention strategies, as well as in tailoring therapy according to a thrombosis outcome risk stratification approach.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias/terapia , Trombose/terapia , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Medição de Risco , Trombose/classificação , Resultado do TratamentoRESUMO
OBJECTIVE: To report the outcomes of an institutional protocol for periprocedural anticoagulant (AC) management in children with acute lymphoblastic leukemia (ALL). STUDY DESIGN: Children being treated for ALL who received full-dose (therapeutic) anticoagulation before undergoing at least 1 lumbar puncture (LP) were included in this retrospective cohort study. The main outcome was the risk of traumatic LP; exploratory analysis included the risks of symptomatic spinal hematoma and progression/recurrence of the thrombotic event. Analyses were conducted using logistic regression analysis with a generalized estimating equation approach. RESULTS: Twenty-two children with ALL receiving an AC underwent a total of 396 LPs. Although traumatic LP was associated with full-dose AC therapy in univariable analysis, a multiple logistic regression model controlling for other risk factors for traumatic LP showed that AC therapy was not significantly associated with the risk of traumatic LP when the ACs were held as per the institutional protocol. No patient developed symptomatic spinal hematoma. Exploratory analysis revealed that AC dose, a likely marker of thrombus burden, was significantly associated with progression/recurrence of the thrombotic event in univariable analysis. CONCLUSION: In our cohort, recent AC therapy was not statistically associated with an increased risk of bleeding after LP when following a specific protocol for periprocedural AC management. The risk associated with the progression/recurrence of thromboembolic events requires further evaluation.