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Background: The Italian Registry of Thrombosis in Children (RITI) was established by a multidisciplinary team with the aims of improving knowledge about neonatal and paediatric thrombotic events in Italy and providing a preliminary source of data for the future development of specific clinical trials and diagnostic-therapeutic protocols., Materials and Methods: We analysed the subset of RITI data concerning paediatric systemic venous thromboembolic events that occurred between January 2007 and June 2013., Results: Eighty-five deep venous thromboses and seven pulmonary emboli were registered in the RITI. A prevalence peak was observed in children aged 10 to 18 years and, unexpectedly, in children aged 1 to 5 years. A central venous line was the main risk factor (55% of venous thromboembolic events); surgery (not cardiac) (25%), concomitant infections (23%) and malignancy (22%) were the clinical conditions most often associated with the onset of venous thromboembolism. There was a diagnostic delay of more than 24 hours in 37% of the venous thromboembolic events. Doppler ultrasound was the most widely used test for the objective diagnosis of deep venous thrombosis (87%). Antithrombotic therapy was administered in 96% of venous thromboembolic events, mainly low molecular weight heparin (60%). In 2% of cases recurrences occurred, while post-thrombotic syndrome developed in 8.5% of cases., Discussion: Although the data from the RITI are largely in agreement with published data, peaks of prevalence of thrombosis, risk factors and objective tests used for the diagnosis showed some peculiarities which may deserve attention.

Objective: To evaluate clinical data and associated risk conditions of noncerebral systemic venous thromboembolism (VT), arterial thromboembolism (AT), and intracardiac thromboembolism (ICT) in neonates., Study Design: Data analysis of first systemic thromboembolism occurring in 75 live neonates (0-28 days), enrolled in the Italian Registry of Pediatric Thrombosis from neonatology centers between January 2007 and July 2013., Results: Among 75 events, 41 (55%) were VT, 22 (29%) AT, and 12 (16%) ICT; males represented 65%, and 71% were preterm. In 19 (25%), thromboembolism was diagnosed on the first day of life. In this "early onset" group, prenatal-associated risk conditions (maternal/placental disease) were reported in 70% and inherited thrombophilia in 33%. Postnatal risk factors were present in 73%; infections and central vascular catheters in 56% and 54% VT, respectively, and in 67% ICT vs 27% AT (<.05). Overall mortality rate was 15% and significant thromboembolism-related sequelae were reported in 16% of discharged patients., Conclusions: This report from the Registro Italiano Trombosi Infantili, although limited by representing an uncontrolled case series, can be used to develop future clinical trials on appropriate management and prevention of neonatal thrombosis, focusing on obstetrical surveillance and monitoring of critically ill neonates with vascular access. A thrombosis risk prediction rule specific for the neonatal population should be developed through prospective controlled studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Data from large case series of children with cerebral thrombotic events are pivotal to improve prevention, early recognition and treatment of these conditions. The Italian Registry of Pediatric Thrombosis (R. I. T. I.) was established in 2007 by a multidisciplinary team, aiming for a better understanding of neonatal and paediatric thrombotic events in Italy and providing a preliminary source of data for the future development of specific clinical trials and diagnostic-therapeutic protocols. We analysed data relative to the paediatric cerebral thrombotic events of the R. I. T. I. which occurred between January 2007 and June 2012. In the study period, 79 arterial ischaemic stroke (AIS) events (49 in males) and 91 cerebral sinovenous thrombosis (CSVT) events (65 in males) were enrolled in the R. I. T. I. Mean age at onset was 4.5 years in AIS, and 7.1 years in CSVT. Most common modes of presentation were hemiparesis, seizures and speech disturbances in AIS, and headache, seizures and lethargy in CSVT. Most common etiologies were underlying chronic diseases, vasculopathy and cardiopathy in AIS, and underlying chronic diseases and infection in CSVT. Time to diagnosis exceeded 24 hours in 46 % AIS and 59 % CSVT. Overall data from the Italian Registry are in substantial agreement with those from the literature, despite small differences. Among these, a longer time to diagnosis compared to other registries and case series poses the accent to the need of an earlier recognition of paediatric cerebrovascular events in Italy, in order to enable prompt and effective treatment strategies.

Introduction: Ischemic brain lesions might present with unexpected increased signal intensity at MR angiography within the ischemic lesion and secondary parenchymal changes in regions distal to the ischemia itself. We retrospectively investigated the rate and time course of vascular and parenchymal changes in children with isolated middle cerebral artery (MCA) stroke., Methods: Twelve children (mean age at stroke onset 4.8 years, range 0.8-15 years, six females, seven right MCA strokes) suffering from a first ever acute isolated MCA stroke had repeated MR scans (mean scan number, 3.5; range 2-6; mean follow-up, 11 months; range 0.5-24 months)., Results: Ipsilaterally to MCA stroke, we recorded increased vessel signal at MR angiography during first to fourth day in 4/7 children (all had MCA recanalization), corticospinal tract cytotoxic-like edema during second day to second month in 7/11 (three children with globus pallidum ischemia had concomitant substantia nigra changes during second to third week), corticospinal tract T2 abnormalities from fifth day onwards in 9/12, focal thalamic cytotoxic-like edema during fifth day to first month in 5/8, focal thalamic T2 hyperintensity during sixth day to third week in 2/4, and faint T2 hypointensity from second month in 7/10 children., Conclusion: Vascular and secondary parenchymal changes, likely due to luxury perfusion, Wallerian, retrograde, or trans-synaptic degeneration, are common in pediatric MCA stroke population. They might mimic new ischemic lesions or suggest conditions different from stroke leading to diagnostic pitfalls and inappropriate treatment.

Background: The aim of this paper was to monitor comfort in pediatric critical ill patients which is necessary to adequate analgesic and sedative therapy. The primary objective of this prospective observational study was to measure the level of sedation in a Pediatric Intensive Care Unit (PICU) of a tertiary care Hospital, using Comfort Behavioural Scale (CBS) and Bispectral Index (BIS), evaluating the agreement between these tools; secondly we analyzed the correlation of an adequate level of sedation and patient's outcome., Methods: We enrolled 46 patients, mechanically ventilated for almost 12 hours, monitored at a basal level and during a stimulus (tracheal suctioning). As outcome variables we analyzed: length of ventilation and PICU stay, duration of sedative therapy and weaning, time between beginning of sedative administration and start of weaning, presence of infection., Results: Twenty-six percent (doctor CBS score), 34.8% (nurse CBS score) and 73.9% (BIS) of our population were found adequately sedated; none state of undersedation was reported. During the stimulus the percentage of adequately sedated patients according to CBS became 78.2%. CBS level of agreement versus BIS was weak. No significative difference was found between doctor and nurse CBS score. Length of PICU stay and duration of sedative administered were significant shorter in patients adequately sedated at Bispectral Index monitoring; no outcome variable resulted significant looking at CBS score., Conclusion: Our data support the risk of oversedation in critically ill patients and the difference between CBS and BIS, especially in evaluating light oversedation state. The presence of an excessive level of sedation evaluated by BIS was associated with duration of hospitalization and sedative administration.

Varicella zoster virus (VZV) is the only human virus known to replicate in arteries. After the acute infection, the virus persists in a noninfectious latent form in ganglia along the neuraxis, with intermittent periods of reactivation. Both primary and secondary reactivation are associated with stroke in children. These patients, regardless of the chosen treatment, have a high risk of recurrence, particularly those with worsening arterial stenosis. There are no specific therapy protocols for varicella-associated stroke in children, and the use of steroids or antiviral drugs is still controversial. We present a series of 4 children with stroke following varicella infection, with no recurrence and stable vascular stenosis at a mean follow-up of 18 months without steroid treatment. We also analyze possible correlations between anti-protein C, protein S and protein Z autoantibodies, and post-varicella arteriopathy.

The primary aim of this study was to describe the use of the antiplatelet agent clopidogrel in pediatric tertiary care hospitals and to evaluate how it has changed over time. This retrospective cohort study of pediatric inpatients from 2000 to 2009 used the Pediatric Health Information System database (PHIS) which contains data from 42 U.S. tertiary care children's hospitals. Pharmacy billing codes were used to identify hospital admissions during which clopidogrel was administered. Patient demographics and concurrent use of other anticoagulant and antiplatelet drugs were collected. The International Classification of Diseases, ninth edition (ICD-9) codes were used to categorize admissions by potential indications for antiplatelet drugs and to identify bleeding and thrombotic events. From 2001 to 2009, clopidogrel use increased 15-fold, from 6 to 89.5 per 100,000 admissions. Patients with cardiac disease accounted for the largest proportion (75%), followed by stroke (9.4%) and Kawasaki disease (6.1%). Among those with cardiac disease, hypoplastic left heart syndrome (38%) and pulmonary artery anomalies (37%) were the most common. Aspirin was used concurrently during 52% of the admissions, enoxaparin during 9%, and warfarin during 5%. The use of clopidogrel is increasing rapidly among children with cardiovascular diseases. This population has a high risk of bleeding, thrombosis, and mortality. It therefore is imperative that future studies continue to evaluate the safety and efficacy of clopidogrel for these children.

The aim of this study was to assess the prevalence of inherited thrombophilia in 'peri-neonatal arterial ischemic stroke' (AIS), and its possible correlation with type of stroke and long-term neurological outcome. A cohort of twenty-four infants affected by AIS were analysed for risk factors, clinical and neuroradiological features, coagulation and thrombophilia profile and outcome. Two subgroups were considered, based on clinical presentation: infants symptomatic in the neonatal period, acute AIS (aAIS) and those with a delayed presentation (presumed peri-neonatal onset, pAIS). The mean follow-up on patients was 3 yr and 1 month (range 1-15 yr). Inherited thrombophilia, consisting of factor V Leiden and prothrombin G20210A mutations, protein C and/or protein S deficiencies, was detected in 28.6%. A significantly higher prevalence of inherited thrombophilia was observed in infants with pAIS compared with aAIS (Fisher's exact test, P = 0.011). Infants with pAIS had a significantly worse neurological outcome with respect to aAIS (Fisher's exact test, P = 0.014). Inherited thrombophilia was significantly higher in patients with a poor neurological outcome (Fisher's exact test P = 0.002). Although the clinical presentation (aAIS vs. pAIS) was associated with future neurological disabilities, it is the thrombophilia but not the clinical presentation, which remains the only significant prognostic factor in the logistic regression analysis. Although preliminary, these data suggest an association of unfavourable neurological outcome and inherited prothrombotic defects in neonatal AIS. The higher prevalence of inherited thrombophilia identified in pAIS and the worse neurological outcome encourage further investigations in population-based studies.