Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children.

BACKGROUND: The prevalence of children diagnosed with thrombotic events has been increasing in the last decades. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). It is unknown if anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. This is an update of the Cochrane Review published in 2014. OBJECTIVES: To determine the effect of LMWH prophylaxis on the incidence of CVC-related thrombosis and major and minor bleeding complications in children. Further objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related bloodstream infection (CRBSI), other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis) and mortality during therapy. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 May 2019. We undertook reference checking of identified trials to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised trials comparing LMWH to no prophylaxis (placebo or no treatment), or low-dose unfractionated heparin (UFH) either as continuous infusion or flushes (low-dose UFH aims to ensure the patency of the central line but has no systemic anticoagulation activity), given to prevent CVC-related thrombotic events in children. We selected studies conducted in children aged 0 to 18 years. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible studies, which were assessed for study methodology including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: One additional study was included for this update bringing the total to two included studies (with 1135 participants). Both studies were open-label RCTs comparing LMWH with low-dose UFH to prevent CVC-related thrombosis in children. We identified no studies comparing LMWH with placebo or no treatment. Meta-analysis found insufficient evidence of an effect of LMWH prophylaxis in reducing the incidence of CVC-related thrombosis in children with CVC, compared to low-dose UFH (RR 0.68, 95% CI 0.27 to 1.75; 2 studies; 787 participants; low-certainty evidence). One study (158 participants) reported symptomatic and asymptomatic CVC-related thrombosis separately and detected no evidence of a difference between LMWH and low-dose UFH (RR 1.03, 95% CI 0.21 to 4.93; low-certainty evidence; RR 1.17, 95% CI 0.45 to 3.08; low-certainty evidence; for symptomatic and asymptomatic participants respectively). There was insufficient evidence to determine whether LMWH impacts the risk of major bleeding (RR 0.27, 95% CI 0.05 to 1.67; 2 studies; 813 participants; low-certainty evidence); or minor bleeding. One study reported minor bleeding in 53.3% of participants in the LMWH arm and in 44.7% of participants in the low-dose UFH arm (RR 1.20, 95% CI 0.91 to 1.58; 1 study; 158 participants; very low-certainty evidence), and the other study reported no minor bleeding in either group (RR: not estimable). Mortality during the study period was reported in one study, where two deaths occurred during the study period. Both were unrelated to thrombotic events and occurred in the low-dose UFH arm. The second study did not report mortality during therapy per arm but showed similar 5-year overall survival (low-certainty evidence). No additional adverse effects were reported. Other pre-specified outcomes (including CVC occlusion, patency and CRBSI) were not reported. AUTHORS' CONCLUSIONS: Pooling data from two RCTs did not provide evidence to support the use of prophylactic LWMH for preventing CVC-related thrombosis in children (low-certainty evidence). Evidence was also insufficient to confirm or exclude a difference in the incidence of major and minor bleeding complications in the LMWH prophylaxis group compared to low-dose UFH (low and very low certainty respectively). No evidence of a clear difference in overall mortality was seen. Studies did not report on the outcomes catheter occlusion, days of catheter patency, episodes of CRBSI and other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis). The certainty of the evidence was downgraded due to risk of bias of the included studies, imprecision and inconsistency, preventing conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombosis in children.

Different unfractionated heparin doses for preventing arterial thrombosis in children undergoing cardiac catheterization.

BACKGROUND: The role of cardiac catheterization in pediatrics has progressed significantly over the last two decades, evolving from a primary diagnostic tool to a primary treatment modality in children with congenital heart disease. Vascular complications, particularly arterial thrombosis, are among the most common unwanted post-cardiac catheterization events. In 1974, unfractionated heparin proved to be superior to placebo in decreasing the incidence of arterial thrombosis in pediatric patients. However, the optimal dose of unfractionated heparin to be utilized in this setting remains a matter of controversy. This is an update of the review first published in 2014. OBJECTIVES: To evaluate the use of low-dose (< 100 units/kg) versus high-dose (≥ 100 units/kg) unfractionated heparin administered as an intravenous bolus at the time of initiation of cardiac catheterization (that is, immediately after arterial puncture), with or without subsequent heparin maintenance doses, for the prevention of post-procedural arterial thrombosis in children. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 15 October 2019. We planned to undertake reference checking of identified trials to identify additional studies. No language restrictions were applied. SELECTION CRITERIA: We included randomized or quasi-randomized trials that compared low dose to high dose unfractionated heparin administered prior to cardiac catheterization. We selected studies conducted in children aged 0 to 18 years. DATA COLLECTION AND ANALYSIS: The first screening of potentially eligible studies was conducted by one of the authors (MLA). The second screening, risk of bias assessment and data extraction were independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events, bleeding complications, other complications) were treated as dichotomous variables. The effect measures used were risk ratio (RR), risk difference (RD) and number needed to treat (NNT), with 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified no new studies for inclusion in this review. In total, two studies with a total of 492 participants were included. We had concerns about risk of bias for one of the two studies. The certainty of the evidence for our key outcomes was downgraded to moderate due to risk of bias concerns and imprecision. The confidence interval for the risk of arterial thrombotic events was compatible with benefits of either high or low unfractionated heparin dose regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of the studies reported the frequency of bleeding events and found no clear difference in the incidence of major or minor bleeding events between arms (RR low-dose versus high-dose 2.96, 95% CI 0.12 to 71.34 for major bleeding events; RR low-dose versus high-dose 1.38, 95% CI 0.46 to 4.13 for minor bleeding). This study also reported on the incidence of deep vein thrombosis when comparing the high versus low dose of heparin and reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI 0.01 to 8.28). The other study lacked information about bleeding. Additional side effects of heparin other than bleeding events were not reported in either of the studies. AUTHORS' CONCLUSIONS: Due to the limitations of the current evidence, small number of included studies, and lack of details reported in one study, we are unable to determine the effects of different dosing regimens of unfractionated heparin for the prevention of vascular thrombosis during cardiac catheterization in children. Further adequately powered, randomized clinical trials are needed.

Characteristics of pain, other symptoms and function in pediatric post-thrombotic syndrome.

BACKGROUND: Symptoms and function in pediatric post-thrombotic syndrome (PTS) remain poorly characterized. METHODS: The present cross-sectional study describes the characteristics of pain, other symptoms, and impaired function in pediatric PTS in a cohort of children with history of upper or lower limb deep vein thrombosis and PTS diagnosis. The frequency of clinical findings was compared between patients with and without pain, and between patients with upper and lower extremity PTS. RESULTS: Seventy-eight children were included in the study. The most common PTS symptoms were pain, tired limb and heaviness. Symptoms were usually reported to occur at mid-day or later and were typically triggered by exercise. Half the patients reported impaired endurance. Pain was reported by 45% of patients and was usually mild-moderate. Heaviness, tightness, tired limb, paresthesia, self-reported limb edema, and impaired endurance were most common in patients with than in patients without pain. Conversely, activity and participation scores, skin redness, and clinician-assessed limb edema did not differ between patients with and without pain. Lastly, there was no difference in pain intensity or frequency of paresthesia, swelling, heaviness, or impaired endurance when comparing the upper and lower extremities. CONCLUSION: Tired limb, heaviness, pain, and impaired endurance were the most frequent clinical findings in pediatric PTS. Frequency of symptoms and pain intensity did not differ between upper and lower extremities. Pain was associated with the presence of other symptoms and impaired function, but not with activity limitation and participation restriction. Better tools are needed to measure these two latter aspects of health.

Assessment of limb edema in pediatric post-thrombotic syndrome.

BACKGROUND: Pediatric tools for diagnosis of post-thrombotic syndrome (PTS) include the assessment of limb edema as a symptom (patient/proxy-reported) and as a sign. However, it is unclear whether these two approaches refer to the same clinical aspect of PTS. This could result in overestimation of disease severity. We sought to evaluate the correlation among different techniques to assess limb edema as a sign and as a symptom in children who sustained upper extremity (UE) or lower extremity (LE) deep vein thrombosis (DVT) and were, therefore, at risk of PTS. METHODS: Limb edema was cross-sectionally measured as a symptom (ie, patient- or proxy-reported) and as a sign (ie, clinician-assessed limb circumference difference, limb volume ratio, bioimpedance spectroscopy ratio (BIS), and durometry ratio) in 140 children at risk of PTS (n = 70 UE-DVT, n = 70 LE-DVT). Item-item correlations were estimated using Pearson or Spearman correlation coefficients, as appropriate, and separately for the UE and LE groups. RESULTS: In the UE-DVT group, proxy-reported swelling correlated weakly to moderately with circumference difference and with volume ratio, but not with BIS ratio. In the LE-DVT group, proxy-reported swelling correlated moderately with thigh circumference difference and volume ratio, and patient-reported swelling correlated moderately with BIS ratio. CONCLUSION: Our findings suggest that patient/proxy-reported and clinician-assessed limb edema measure slightly different aspects of PTS, justifying their inclusion in pediatric PTS tools. In addition, proxy-reported swelling was in closer agreement with clinician-assessed total limb size (ie, observed edema), and patient-reported swelling in the LE seemed to reflect limb fluid content (ie, perceived edema).

Postthrombotic syndrome following upper extremity deep vein thrombosis in children.

Despite its relatively estimated high occurrence, the characterization of pediatric upper extremity deep vein thrombosis (UE-DVT) and of UE postthrombotic syndrome (PTS) is still lacking. We investigated the occurrence, characteristics, and predictors of UE-PTS in a cohort of children with objectively confirmed UE-DVT. Patients were analyzed in 3 groups according to DVT pathogenesis and neonatal status: primary (G1), secondary neonates (G2neonates), and non-neonates (G2non-neonates). A total of 158 children (23 G1, 25 G2neonates, and 110 G2non-neonates) were included. The most common triggering factors were effort-related (87%) in G1 and central lines in G2neonates (100%) and in G2non-neonates (92%). PTS scores ≥1, as per the Modified Villalta Scale, were identified in 87% of primary patients, 16% of G2neonates, and 49% of G2non-neonates. Survival analysis showed that the time to PTS score ≥1 significantly differed among group (log-rank test P < .0001). A multivariable logistic regression showed that DVT pathogenesis and imaging-determined degree of thrombus resolution at the end of therapy were independent predictors of a PTS score ≥2. In conclusion, pediatric UE-PTS frequency and severity depend on UE-DVT pathogenesis (primary/secondary) and, within the secondary group, on patient's age. Line-related UE-PTS has a more benign course, particularly in neonates.

Assessment of the outcomes associated with periprocedural anticoagulation management in children with acute lymphoblastic leukemia.

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.

Different unfractionated heparin doses for preventing arterial thrombosis in children undergoing cardiac catheterization.

BACKGROUND: The role of cardiac catheterization in pediatrics has progressed significantly over the last two decades, evolving from a primary diagnostic tool to a primary treatment modality in children with congenital heart disease. Vascular complications, particularly arterial thrombosis, are among the most common unwanted post-cardiac catheterization events. In 1974, unfractionated heparin proved to be superior to placebo in decreasing the incidence of arterial thrombosis in pediatric patients. However, the optimal dose of unfractionated heparin to be utilized in this setting remains a matter of controversy. OBJECTIVES: To evaluate the use of low-dose (< 100 units/kg) versus high-dose (≥ 100 units/kg) unfractionated heparin administered as an intravenous bolus at the time of initiation of cardiac catheterization (that is, immediately after arterial puncture), with or without subsequent heparin maintenance doses, for the prevention of post-procedural arterial thrombosis in children. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). The authors searched MEDLINE, EMBASE, and the Virtual Health Library. Clinical trials databases and sources of grey literature were searched. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized trials that compared low dose to high dose unfractionated heparin administered prior to cardiac catheterization were included. We selected studies conducted in children aged 0 to 18 years. DATA COLLECTION AND ANALYSIS: The first screening of potentially eligible studies was conducted by one of the authors (MLA). The second screening, quality assessment and data extraction were independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events, bleeding complications, other complications) were treated as dichotomous variables. The effect measures used were risk ratio (RR), risk difference (RD) and number needed to treat (NNT), with 95% confidence intervals (CI). MAIN RESULTS: Two studies with a total of 492 participants were eligible for inclusion. Risk of bias was low for all domains in one of the studies and unclear for the other. One of the trials was stopped early. The quality of evidence for our key outcomes was moderate. The CI for the risk of arterial thrombotic events was compatible with benefits of either high or low unfractionated heparin dose regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of the studies reported the frequency of bleeding events for the cohort of patients and found no statistically significant difference in the incidence of major and minor bleeding events between arms (RR low-dose versus high-dose 1.38, 95% CI 0.46 to 4.13 for minor bleeding; RR low-dose versus high-dose 2.96, 95% CI 0.12 to 71.34 for major bleeding events). This study also reported on the incidence of deep vein thrombosis when comparing the high versus low dose of heparin and reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI 0.01 to 8.28). The other study lacked information about bleeding. Side effects of heparin other than bleeding complications were not reported in either of the studies. AUTHORS' CONCLUSIONS: Due to the limitations of the current evidence, small number of included studies, and lack of details reported in one study, we are unable to determine the effects of different dosing regimens of unfractionated heparin for the prevention of vascular thrombosis during cardiac catheterization in children. A further adequately powered, randomized clinical trial is needed.

Gene discovery in Triatoma infestans.

BACKGROUND: Triatoma infestans is the most relevant vector of Chagas disease in the southern cone of South America. Since its genome has not yet been studied, sequencing of Expressed Sequence Tags (ESTs) is one of the most powerful tools for efficiently identifying large numbers of expressed genes in this insect vector. RESULTS: In this work, we generated 826 ESTs, resulting in an increase of 47% in the number of ESTs available for T. infestans. These ESTs were assembled in 471 unique sequences, 151 of which represent 136 new genes for the Reduviidae family. CONCLUSIONS: Among the putative new genes for the Reduviidae family, we identified and described an interesting subset of genes involved in development and reproduction, which constitute potential targets for insecticide development.

Trombectomía auricular derecha en un recién nacido prematuro de muy bajo peso / Right atrial thrombectomy in a very law birth weight premature neonate

RESUMEN El problema de la trombosis venosa en el período neonatal radica en la limitada y controvertida información sobre sus opciones terapéuticas. Las alternativas incluyen tratamiento de soporte, anticoagulación,trombolisis y, en menor número de casos, cirugía.Más del 80 por ciento de los casos de trombosis se relacionan con catéteres venosos centrales y su presencia constituye un factor de riesgo para el desarrollo de trombosis auricular derecha. Se presenta en este trabajo el caso clínico de un recién nacido prematuro extremo, en quien la elección terapéutica ante una trombosis auricular derecha fue la trombectomía quirúrgica, con circulación extracorpórea e hipotermia profunda

Trombectomía auricular derecha en un recién nacido prematuro de muy bajo peso / Right atrial thrombectomy in a very law birth weight premature neonate

RESUMEN El problema de la trombosis venosa en el período neonatal radica en la limitada y controvertida información sobre sus opciones terapéuticas. Las alternativas incluyen tratamiento de soporte, anticoagulación,trombolisis y, en menor número de casos, cirugía.Más del 80 por ciento de los casos de trombosis se relacionan con catéteres venosos centrales y su presencia constituye un factor de riesgo para el desarrollo de trombosis auricular derecha. Se presenta en este trabajo el caso clínico de un recién nacido prematuro extremo, en quien la elección terapéutica ante una trombosis auricular derecha fue la trombectomía quirúrgica, con circulación extracorpórea e hipotermia profunda(AU)

Síndrome de Stevens-Johnson: experiencia del Hospital Nacional de Niños durante los últimos diez años / Stevens-Johnson syndrome: experience of Hospital Nacional de Niños during the 10 years

Objetivo: Conocer la experiencia del Hospital de Niños acerca del SSJ en los últimos 10 años. Revisar las recomendaciones en relación al manejo del SSJ. Métodos: Se realizó un análisis retrospectivo de los expedientes de los pacientes egresados con el diagnóstico de SSJ, de enero de 1987 a enero de 1997, analizando edad, sexo, procedencia, exposición previa a medicamentos, manifestaciones clínicas, complicaciones y tratamiento. Resultados: Durante 10 años, 26 pacientes fueron egresados del Hospital Nacional de Niños con el diagnóstico de SSJ. 69 por ciento (18/26) fueron varones. La mayoría de los niños provenía de San José. El promedio de edad fue de 5 años, con una mediana de 4 años, y una desviación estandar (DS) de +/- 3.6. La historia de exposición previa a medicamentos fue positiva en el 77 por ciento de los pacientes, siendo los antibióticos los más usados (50 por ciento), seguidos de los anticonvulsivantes (40 por ciento). 69 por ciento de los pacientes tenía historia previa de infección respiratoria superior. Se usaron esteroides en el 42 por ciento de los pacientes, en éstos la estancia hospitalaria fue 6 +/- 7 vrs 11 +/- 11.4. días en aquellos que no los recibieron, p=0.01. Las complicaciones fueron menos frecuentes en el grupo que recibió esteroides (9 por ciento), comparado con el que no recibió esteroides (33 por ciento), p=0.1. No se reportaron muertes por esta patología. Conclusiones: El diagnóstico y particularmente el uso de esteroides en el manejo de pacientes con SSJ es controversial. En esta enfermedad la muerte puede ocurrir debido a varias causas, entre ellas la infección secundaria y el daño visceral. En esta serie, los esteroides parecieron ser benéficos, sin embargo, son necesarios estudios controlados, para establecer su verdadera unidad