Promising biomarkers for the prediction of catheter-related venous thromboembolism in hospitalized children: An exploratory study.

BACKGROUND: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC) being the strongest risk factor. Current tools are not sufficient to predict VTE risk. The utility of biomarkers in predicting CVC-related VTE has been minimally explored. Our objective is to determine the utility of microparticles (MPs), factor VIII (FVIII) activity, and thrombin generation (TG) in prospectively predicting VTE occurrence in hospitalized children with CVCs. PROCEDURE: In this nested case-control pilot study, consecutive hospitalized children needing CVC placement (1 month to 21 years) were enrolled. Venous samples were collected prior to or within 24 h of CVC placement. MPs were measured using factor Xa initiated clot-based assay. FVIII was measured using a one-stage clot-based assay. TG was measured using calibrated automated thrombogram. RESULTS: There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07 vs 0.95 ± 0.21, P = .4), while FVIII (461 ± 120 vs 267 ± 130, P = .02), peak thrombin (418 ± 89 vs 211 ± 101, P = .001), endogenous thrombin potential (ETP) (1828 ± 485 vs 1282 ± 394, P = .03), and velocity index (VI) (182 ± 28 vs 75 ± 53, P = .001) were higher in subjects with CVC-related VTE compared to those without CVC-related VTE. Sensitivity/specificity analysis revealed optimal cutoff values for XaCT ratio (0.75), FVIII (370), ETP (1680), peak (315), and VI (130), with receiver operating characteristic area under the curve values >0.9. CONCLUSION: MPs, FVIII, and TG can potentially predict pediatric CVC-related VTE in a prospective fashion. Stratification according to VTE risk may aid in guiding preventative efforts in future studies.

The role of patient and healthcare professionals in the era of new hemophilia treatments in developed and developing countries.

Medical decisions in hemophilia care are primarily related to the type of factor replacement and treatment regimen. With the growing number of treatment options for patients with hemophilia, decision making is more complex and requires careful consideration of benefits, risks, and patient goals. Shared decision making and decision-aid tools facilitate patient and healthcare provider communication. In this review, the overall role of shared decision making in medicine is outlined, with special emphasis on models for practical implementation. Examples of shared decision making in hemophilia are outlined, and application to new therapeutics is discussed through a case-based approach.

Pediatric superior vena cava syndrome: An evidence-based systematic review of the literature.

Superior vena cava syndrome (SVCS) results in vascular, respiratory, and neurologic compromise. A systematic search was conducted to determine the prevalence of pediatric SVCS subtypes and identify clinical characteristics/treatment strategies that may influence overall outcomes. Data from 101 case reports/case series (142 patients) were analyzed. Morbidity (30%), mortality (18%), and acute complications (55%) were assessed as outcomes. Thrombosis was present in 36%, with multi-modal anticoagulation showing improved outcome by >50% (P = 0.004). Infant age (P = 0.04), lack of collaterals (P = 0.007), acute complications (P = 0.005), and clinical presentation may have prognostic utility that could influence clinical decisions and surveillance practices in pediatric SVCS.

In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure.

: Thromboelastography (TEG) is a global assay used for evaluating features of clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin that has not been studied in neonates using a sophisticated global assay, such as TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and qualitative characteristics. Our aim was to compare the TEG clotting profile of neonatal and adult platelet-poor plasma when exposed to different concentrations of dabigatran. We used commercially collected adult pooled plasma and neonatal cord blood collected from placentas of healthy full term newborns. Platelet-poor plasma was isolated, pooled, and frozen. Prior to experiment, plasma was thawed and filtered. A reaction mixture of CaCl2, corn trypsin inhibitor, tissue factor, and dabigatran in imidazole buffer was mixed with plasma in a TEG cup. Time to clot initiation (R-time), speed of clot strengthening (α-angle), and maximum clot strength (maximal amplitude) were measured. Scanning electron microscopy was performed to evaluate fibrin clot structure. Without dabigatran, there was no significant difference in TEG measurements between neonatal and adult samples. However, neonatal plasma clotting with dabigatran had slower onset, slower speed, and weaker clots that were more porous with thicker fibers, compared with adult plasma clotting. Thus, neonatal plasma may be more sensitive to dabigatran as assessed by our in-vitro TEG study.

Safety of deep sedation in young children with sickle cell disease: a retrospective cohort study.

OBJECTIVE: To assess the rates and types of complications associated with deep sedation in children with sickle cell disease (SCD) and to explore potential risk factors. STUDY DESIGN: This was a retrospective cohort study of children with SCD and a comparison group of children without SCD who underwent magnetic resonance imaging with deep sedation. The rates of general and SCD-associated sedation complications were calculated, and potential associated clinical and laboratory variables were assessed. RESULTS: A total of 162 sedation records in 94 subjects with SCD and 324 sedation records in 321 subjects without SCD were assessed (mean age, 4.3 years in both groups). Pentobarbital, fentanyl, and midazolam were used in the majority of sedation episodes without routine presedation transfusion. Sedation-related complication rates did not differ significantly between the SCD and comparison groups. Within 1 month after the sedation procedure, 17 children (10%) experienced a vaso-occlusive pain episode (VOE), and 2 children (1.2%) developed acute chest syndrome. Preprocedure and postprocedure rates of these complications did not differ significantly. Subjects who developed VOE after sedation had a significantly higher VOE rate before sedation, but no other significant clinical or laboratory risk factors were identified. CONCLUSION: Deep sedation in young children with SCD using a standard protocol is safe, with a sedation-related complication rate comparable to that of the general pediatric population. The observed rate of VOE, although not significantly higher than expected, warrants further investigation.