Association of thrombophilia and catheter-associated thrombosis in children: a systematic review and meta-analysis.

UNLABELLED: Essentials It is unclear if thrombophilia increases the risk of catheter-associated thrombosis in children. We conducted a meta-analysis on thrombophilia and pediatric catheter-associated thrombosis. Presence of ≥1 trait confers additional risk of venous thrombosis in children with catheters. Limitations of included studies preclude us from recommending routine thrombophilia testing. SUMMARY: Background The association between thrombophilia and deep vein thrombosis (DVT) associated with central venous catheter (CVC) use, the most important pediatric risk factor for thrombosis, is unclear in children. Pediatric studies with small sample sizes have reported conflicting results. We sought to evaluate whether, among children with CVCs, thrombophilia increases the risk of CVC-associated DVT (CADVT). Materials and methods We systematically searched MEDLINE, EMBASE, the Web of Science, the Cochrane Central Register for Controlled Trials, PubMed and reference lists for controlled studies published from the inception of the database until September 2015. Included were studies of children aged <21 years with CVCs who were systematically tested for thrombophilic traits that are commonly screened for in clinical practice. Pooled prevalence rates and pooled odds ratios (pORs) of CADVT with thrombophilia were estimated by use of a random effects model. Results We analyzed 16 cohort studies with 1279 children, 277 of whom had CADVT, and with 12 traits tested. There was significant heterogeneity in the included studies. The presence of one or more traits was associated with CADVT (pOR 3.20; 95% confidence interval [CI] 1.56-6.54). Although the prevalence of most traits was < 0.10, children with protein C deficiency, elevated factor VIII levels and the FV Leiden mutation had an increased prevalence of CADVT. The association with thrombophilia seemed to be stronger for symptomatic CADVT (pOR 6.71; 95% CI 1.93-23.37) than for asymptomatic CADVT (pOR 2.14; 95% CI 1.10-4.18). Conclusions On the basis of the low prevalence of specific traits, the relatively weak association with CADVT, and the limitations of the included studies, we cannot recommend routine testing of thrombophilias in children with CADVT.

[Thromboprophylaxis in critically ill children in Spain and Portugal]. / Utilización de medidas de tromboprofilaxis en niños críticamente enfermos en España y Portugal.

INTRODUCTION: Although critically ill children may be at risk from developing deep venous thrombosis (DVT), data on its incidence and effectiveness of thromboprophylaxis are lacking. OBJECTIVE: To describe the use of thromboprophylaxis in critically ill children in Spain and Portugal, and to compare the results with international data. MATERIAL AND METHODS: Secondary analysis of the multinational study PROTRACT, carried out in 59 PICUs from 7 developed countries (4 from Portugal and 6 in Spain). Data were collected from patients less than 18 years old, who did not receive therapeutic thromboprophylaxis. RESULTS: A total of 308 patients in Spanish and Portuguese (Iberian) PICUS were compared with 2176 admitted to international PICUs. Risk factors such as femoral vein (P=.01), jugular vein central catheter (P<.001), cancer (P=.03), and sepsis (P<.001), were more frequent in Iberian PICUs. The percentage of patients with pharmacological thromboprophylaxis was similar in both groups (15.3% vs. 12.0%). Low molecular weight heparin was used more frequently in Iberian patients (P<.001). In treated children, prior history of thrombosis (P=.02), femoral vein catheter (P<.001), cancer (P=.02) and cranial trauma or craniectomy (P=.006), were more frequent in Iberian PICUs. Mechanical thromboprophylaxis was used in only 6.8% of candidates in Iberian PICUs, compared with 23.8% in the international PICUs (P<.001). CONCLUSIONS: Despite the presence of risk factors for DVT in many patients, thromboprophylaxis is rarely prescribed, with low molecular weight heparin being the most used drug. Passive thromboprophylaxis use is anecdotal. There should be a consensus on guidelines of thromboprophylaxis in critically ill children.

Central venous catheter-related thrombosis and thromboprophylaxis in children: a systematic review and meta-analysis.

OBJECTIVES: In preparation for a pediatric randomized controlled trial on thromboprophylaxis, we determined the frequency of catheter-related thrombosis in children. We also systematically reviewed the pediatric trials on thromboprophylaxis to evaluate its efficacy and to identify possible pitfalls in the conduct of these trials. PATIENTS/METHODS: We searched MEDLINE, EMBASE, Web of Science and the Cochrane Central Register for Controlled Trials for articles published until December 2013. We included cohort studies and trials on patients aged 0-18 years with central venous catheters who underwent active surveillance for thrombosis with radiologic imaging. We estimated the pooled frequency of thrombosis and the pooled risk ratio (RR) with thromboprophylaxis by using a random effects model. RESULTS: From 2651 articles identified, we analyzed 37 articles with 3128 patients. The pooled frequency of thrombosis was 0.20 (95% confidence interval [CI] 0.16-0.24). In 10 trials, we did not find evidence that heparin-bonded catheters (RR 0.34; 95%CI 0.01-7.68), unfractionated heparin (RR 0.93; 95% CI 0.57-1.51), low molecular weight heparin (RR 1.13; 95% CI 0.51-2.50), warfarin (RR 0.85; 95%CI 0.34-2.17), antithrombin concentrate (RR 0.76; 95% CI 0.38-1.55) or nitroglycerin (RR 1.53; 95%CI 0.57-4.10) reduced the risk of thrombosis. Most of the trials were either not powered for thrombosis or were powered to detect large, probably unachievable, reductions in thrombosis. Missing data on thrombosis also limited these trials. CONCLUSIONS: Catheter-related thrombosis is common in children. An adequately powered multicenter trial that can detect a modest, clinically significant reduction in thrombosis is critically needed. Missing outcome data should be minimized in this trial.

Blood glucose as a marker of venous thromboembolism in critically ill children.

BACKGROUND: The ability to predict the development of venous thromboembolism is highly desirable. OBJECTIVE: We aim to determine the association between hyperglycemia and venous thromboembolism in non-diabetic critically ill children. PATIENTS/METHODS: We conducted a retrospective cohort study that included children in the pediatric intensive care unit on a vasopressor or mechanical ventilator and without history of diabetes mellitus or prior diagnosis of thrombosis. Based on maximum blood glucose > 150 mg dL(-1) while admitted to the unit, children were categorized as hyperglycemic or non-hyperglycemic. The primary outcome was development of venous thromboembolism while admitted to the unit. We determined the association between hyperglycemia and venous thromboembolism using logistic regression models adjusting for selected subject characteristics. RESULTS: Of the 789 subjects analyzed, 34 subjects developed venous thromboembolism (incidence, 4.3%; 95% confidence interval, 3-6%). Venous thromboembolism was more likely to develop in hyperglycemic subjects compared with non-hyperglycemic subjects. A total of 31 subjects (6.2%; 95% confidence interval, 4.2-8.7%) developed venous thromboembolism after becoming hyperglycemic compared with three non-hyperglycemic subjects with venous thromboembolism (1%; 95% confidence interval, 0.2-3%). When adjusted for age, diagnosis, presence of central venous catheter, prophylactic antithrombotic use and severity of illness, the odds ratio of venous thromboembolism with hyperglycemia was 4.1 (95% confidence interval, 1.2-14.1). For every 10 mg dL(-1) increase in maximum blood glucose, the adjusted odds ratio of venous thromboembolism was 1.04 (95% confidence interval, 1.01-1.06). CONCLUSION: Hyperglycemia is associated with venous thromboembolism in critically ill non-diabetic children. Maximum blood glucose is a potential predictor of venous thromboembolism in this population.