Secondary Anticoagulation Prophylaxis for Catheter-Related Thrombosis in Pediatric Intestinal Failure: Comparison of Short- Vs Long-Term Treatment Protocols.

INTRODUCTION: Catheter-related thrombosis (CRT) is a devastating complication of central venous catheters in children with intestinal failure (IF), but the optimal preventive therapy of CRT is unknown. This study assessed the efficacy and safety of 2 protocols of secondary anticoagulation prophylaxis with low-molecular-weight heparin (LMWH). METHODS: This is a comparative cohort study of children from 2 IF programs who received secondary anticoagulation prophylaxis with LMWH for CRT. The short-term protocol group (N = 13) received therapeutic dosing until thrombus resolution or ≤3 months. In the long-term protocol group (N = 26), prophylactic dosing continued until line removal. Patients underwent routine annual vascular ultrasound and were followed for ≥1 year. The primary outcome was development of secondary thrombosis; post hoc analysis assessed rates of secondary thrombosis at 12 months. RESULTS: Patient demographics were similar between groups. Secondary thrombosis occurred in 8 of 13 (62%) patients in the short-term group and in 9 of 26 (35%) in the long-term protocol group (P = .019) in a median time of 144.5 and 689 days, respectively (P = .01). Secondary thrombosis within 12 months occurred in 7 of 13 (54%, short term) and 2 of 26 (8%, long term) patients (P = .001). Secondary thrombosis was associated with catheter replacements (23.5 vs 5.5 catheters per 1000 catheter days; P = .016) and longer daily parenteral nutrition (PN) infusion (24 vs 15.25 hours; P = .044). Compliance was good (>80% of doses) in 92% of patients. CONCLUSIONS: Long-term secondary anticoagulation prophylaxis with LMWH reduces the incidence of secondary thrombosis and should be considered in children with CRT that require PN for prolonged periods of time.

Risk factors for the development of hospital-acquired pediatric venous thromboembolism-Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis.

INTRODUCTION: Hospital-acquired venous thromboembolism (HA-VTE) in children comprises multiple risk factors that should not be evaluated separately due to collinearity and multiple cause and effect relationships. This is one of the first case-control study of pediatric HA-VTE risk factors using a Directed Acyclic Graph (DAG) analysis. MATERIAL AND METHODS: Retrospective, case-control study with 22 cases of objectively confirmed HA-VTE and 76 controls matched by age, sex, unit of admission, and period of hospitalization. Descriptive statistics were used to define distributions of continuous variables, frequencies, and proportions of categorical variables, comparing cases and controls. Due to many potential risk factors of HA-VTE, a directed acyclic graph (DAG) model was created to identify confounding, reduce bias, and increase precision on the analysis. The final model consisted of a DAG-informed conditional logistic regression. RESULTS: In the initial conventional univariable model, the following variables were selected as potential risk factors for HA-VTE: length of stay (LOS, days), immobility, ICU admission in the last 30 days, LOS in ICU, infection, central venous catheter (CVC), number of CVCs placed, L-asparaginase, heart failure, liver failure, and nephrotic syndrome. The final model using the set of variables selected by DAG analysis revealed LOS (OR = 1.106, 95%CI = 1.021-1.198, p = 0.013), L-asparaginase (OR = 26.463, 95%CI = 1.609-435.342, p = 0.022), and nephrotic syndrome (OR = 29.127, 95%CI = 1.044-812.508, p = 0.004) as independent risk factors for HA-VTE. CONCLUSION: The DAG-based approach was useful to clarify the influence of confounders and multiple causalities of HA-VTE. Interestingly, CVC placement-a known thrombotic risk factor highlighted in several studies-was considered a confounder, while LOS, L-asparaginase use and nephrotic syndrome were confirmed as risk factors to HA-VTE. Large confidence intervals are related to the sample size; however, the results were significant.

Effectiveness and Safety of Primary Thromboprophylaxis in Children with Cancer: A Systematic Review of the Literature and Network Meta-Analysis.

Thromboembolism (TE) is a well-recognized complication of pediatric cancer and can lead to mortality and excess morbidity. There is conflicting evidence about the effectiveness and safety of thromboprophylaxis in children. We conducted a systematic literature review and network meta-analysis of primary pharmacological thromboprophylaxis in children and adolescents (0-21 years) with cancer. The primary outcomes were objectively proven TE and major bleeding. The network meta-analysis included comparisons of multiple alternatives simultaneously: antithrombin (AT) replacement, low molecular weight heparin (LMWH), vitamin K antagonists (VKAs), and standard of care (SOC) defined as no thromboprophylaxis or low-dose heparin for catheter patency. Six articles describing 1,318 patients were included (mean age: 6.7 years, 56.7% male). Acute lymphoblastic leukemia was the underlying diagnosis in 97.5% of patients. All studies were considered at moderate or high risk of bias. LMWH was the only agent associated with lower odds of TE compared with SOC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.06-0.81). No statistically significant difference was detected between other thromboprophylaxis modalities and SOC. Tau2 and I 2 suggested a high degree of heterogeneity. No statistically significant differences in the odds of major bleeding were found between AT replacement, LMWH, VKA, and SOC. Current evidence suggests that low-dose LMWH is effective and safe to prevent TE in children with cancer but is insufficient to conclude if AT replacement or VKA are effective thromboprophylaxis options. Further research, notably randomized controlled trials enrolling children with diverse types of cancer, is crucially needed.