Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies.

BACKGROUND: The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. METHODS AND RESULTS: A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99). CONCLUSIONS: The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated.

Long-term treatment of thrombosis with enoxaparin in pediatric and adolescent patients.

Thrombosis is a rare event in childhood and adolescence. Nevertheless, increasing numbers of invasive diagnostic and therapeutic procedures also result in increasing numbers of thromboses in pediatric cases, necessitating effective antithrombotic treatment regimens. In recent years, low-molecular-weight heparins (LMWH) in particular have been proved to be a safe and effective alternative to unfractioned heparins. However, the application of LMWH in pediatric patients has not been supported by a single controlled study so far. Furthermore, there is no official approval of these drugs for children. In this pilot study 27 children with deep venous thromboses (DVT) were treated with the LMWH enoxaparin at a dosage of 1.5 mg/kg body weight b.i.d. in neonates and infants and 1 mg/kg body weight b.i.d. in children. This dosage was lowered for prophylaxis if therapeutic success was achieved. The aim of the study was to investigate both, efficacy with respect to patency rates and safety during acute and long-term follow-up. Sufficient therapeutic success required a rapid production of anti-Xa target activity and was reached in 85% of the treated patients, who showed patency of the affected vessel at last follow-up. The mean duration of treatment with full dosage was 16.5 days, followed by prophylaxis over a mean duration of 9.8 months. Rethrombosis or adverse events including heparin-induced thrombocytopenia were not observed in any patient. In conclusion, enoxaparin provides an effective and safe alternative to unfractioned heparins in the treatment of thrombosis in infancy, childhood and adolescence.

Prognosis of brain stem lesion in children with head injury.

INTRODUCTION: Traumatic brain stem lesions (tBSL) in children are thought to be a rare phenomenon. This prospective study analyzed the frequency and significance of such lesions on early magnetic resonance imaging (MRI) after severe head injury, since CT fails to demonstrate these lesions. METHODS: In 30 consecutive children comatose after head injuries, MRI was performed within 8 days of the injury. RESULTS: The incidence of tBSL was 60%. When the lesion affected the pons or caudal portions of medulla oblongata bilaterally, mortality was 100%. The presence of tBSL significantly correlated with the duration of coma and the categories of outcome, as indicated by the Glasgow Outcome Score. The frequency and the distribution of tBSL in children were similar to adults. CONCLUSION: Magnetic resonance imaging appears to be of high predictive value after severe pediatric head injuries.

Arterial ischemic stroke in neonates, infants, and children: an overview of underlying conditions, imaging methods, and treatment modalities.

Conditions associated with arterial ischemic stroke (AIS) in children include congenital heart malformations, sickle cell disease, and meningitis, although around half of all cases are cryptogenic. Up to 80% of children with ischemic stroke have cerebrovascular disease, and case control studies demonstrate an association of arterial ischemic stroke in children with hereditary prothrombotic risk factors and infections such as Varicella. Conventional risk factors, such as hypertension and dyslipidemia, may also play a role and most children have several potential triggers rather than a single cause. Treatment recommendations are based on small case series or have been adapted from adult stroke studies; there are no evidence-based data on efficacy in children. Low-dose aspirin appears to be relatively safe. Anticoagulation with heparins, for example, low-molecular-weight heparin or warfarin, may be indicated in children with cardioembolic stroke, arterial dissection, or persistent hypercoagulable states, and blood transfusion has a role in patients with sickle cell disease. Tissue plasminogen activator has been used in a few patients within 3 hours of the onset of symptoms. At present, the benefit of treatment has to be weighed against the risk for each patient, but randomized controlled trials for primary prevention, acute treatment, and secondary prevention of pediatric ischemic stroke are urgently needed.