CVC-related Venous Thromboembolism Research Articles

Venous Thromboembolism in Pediatric Cancer Patients with Central Venous Catheter-A Systematic Review and Meta-analysis.

Pediatric cancer patients hold an increased risk of venous thromboembolism (VTE) due to their cancer. Central venous catheters (CVCs) further increase the VTE risk. This systematic literature review elucidates the VTE incidence in pediatric cancer patients with CVC. MEDLINE and EMBASE were searched in August 2020 without time limits. We included studies reporting original data on patients ≤18 years with any CVC type and any cancer type, who were examined for VTE with ≥7 days follow-up. In total, 682 unique records were identified, whereof 189 studies were assessed in full text. Altogether, 25 studies were included, containing 2,318 pediatric cancer patients with CVC, of which 17% suffered VTE. Fifteen studies (n = 1,551) described CVC-related VTE and reported 11% CVC-related VTE. Concerning cancer type, 991 children suffered from acute lymphoblastic leukemia (ALL) and 616 from solid tumors. Meta-analysis revealed VTE incidence (95% confidence interval) of 21% (8-37) for ALL and 7% (0.1-17) for solid tumors. Additionally, 20% of children with tunneled or nontunneled CVC and 12% of children with implantable ports suffered VTE. In conclusion, pediatric cancer patients with CVC have substantial VTE risk. Children with ALL and CVC have higher VTE incidence than children with solid tumors and CVC. Implantable port catheter should be preferred over tunneled or nontunneled CVC to reduce VTE risk. Thrombophilia investigation does not seem relevant in pediatric cancer patients with CVC and VTE. To prevent VTE, intensified catheter care is recommended, especially in children with ALL.

Central Venous Catheters, a Major Culprit for Pediatric Venous Thrombosis: A Report from the Children's Hospital Acquired Thrombosis (CHAT) Project

Introduction: Incidence of venous thromboembolism (VTE), a potentially life-threatening condition, has increased in hospitalized pediatric patients by over 70% in the last decade leading to increased morbidity, mortality, and longer hospitalizations. In contrast to standardized thromboprophylaxis interventions for hospitalized adults, routine implementation of VTE prevention strategies have not been established in children. To develop a risk-prediction model for pediatric hospital-acquired VTE (HA-VTE) and identify a high-risk group in need of thromboprophylaxis, an observational case-cohort study was created, using the multi-institutional Children's Hospital Acquired Thrombosis (CHAT) Registry. Preliminary CHAT data confirm prior reports that central venous catheters (CVCs) are the greatest risk factor for pediatric HA-VTE. We describe clinical and CVC characteristics for Registry subjects with a CVC-related HA-VTE.Methods: An institutional review board-approved, multi-center CHAT Registry was created for this project to collect retrospective clinical and laboratory data on hospitalized subjects age 0-21 years diagnosed with imaging-confirmed HA-VTE, along with admission year matched controls. Seven hundred and fifty HA-VTE subjects hospitalized since January 1, 2012 are included in the Registry. Data include demographics (age and past medical history); hospital course (duration, infection, mobility, surgeries, trauma, etc.); VTE specifics (location, symptoms, treatment, prophylaxis); CVC details (type, brand, lumen number, duration, infection history); and pertinent laboratory data (thrombophilia and coagulation testing). Pertinent CVC related data were selected for analysis.Results: To date, 658 subjects with HA-VTE have been entered into the CHAT Registry from 01/01/12 to 07/01/2017 from five pediatric tertiary care centers. CVC-VTE was identified in 486 (74%) subjects. Most subjects with a CVC-VTE were male (58%) and the median age at diagnosis was 2 years (IQR 0.3-12.7). Infants <1 year of age accounted for 214 (44%) of CVC-VTE cases (Figure 1). In contrast, subjects diagnosed with a non-CVC-related VTE had a median age of 5 years (IQR 0.3-13.3) at diagnosis, with only 45 (29%) being <1 year. The average time from CVC placement to VTE diagnosis was 23 days. Time from femoral line placement to VTE was 7 days, peripherally inserted central catheters (PICC) placement to VTE was 16 days and tunneled line to VTE was 114 days. Mean hospital length of stay was 48 days for those diagnosed with a CVC-VTE.Subjects with PICCs made up 62% (310) of the CVC-VTE cases and 19% (95) were in subjects with femoral catheters (Figure 2). The majority of CVC-VTEs, 336 (67%), were with multi-lumen CVCs.Upper extremity CVCs were placed in 271 (54%) cases and 203 (41%) were in the lower extremity. The remaining 26 (5%) had CVCs in the umbilical vein or were unknown. CVC's were found to have a malfunction (damage to the line, fibrin sheath, medication precipitation or other blockage) prior to VTE diagnosis in 122 cases (24%), and tissue plasminogen activator (tPA) was used in 91 (75%) cases of malfunction.Conclusions: CVCs are a prominent risk factor for pediatric HA-VTE, yet a paucity of evidence exists to guide clinicians toward strategies to decrease pediatric CVC-VTE. Our preliminary analysis has shown the majority of subjects with a CVC-related HA-VTE were male, had a PICC, and almost half were less than 1 year of age. Subjects also tended to have multi-lumen CVCs placed in the upper extremity. This novel analysis of specific CVC characteristics in CVC-related HA-VTE among hospitalized patients from the CHAT Registry represents a first step in determining the true risk factors for CVC-related VTE in children.Once all control subjects are entered a more robust analysis of risk factors will be performed and a VTE risk prediction model will be created and prospectively validated for HA-VTE, including a specific CVC-related VTE model. This information will be essential for future risk-prediction models of pediatric HA-VTE that may guide randomized control trials to evaluate safety and efficacy of various thromboprophylaxis strategies in this population. [Display omitted] DisclosuresJaffray:CSL Behring: Consultancy; Bayer: Consultancy, Speakers Bureau. Croteau:ATHN/Hemophilia of Georgia: Research Funding; Aptevo, Baxalta/Shire, Bayer, CSL Behring, Genentech, Novo Nordisk, Octapharma, Pfizer: Consultancy; Octapharma: Honoraria; Baxalta, Dimension Therapeutics, Genentech, Pfizer: Research Funding. Silvey:Pfizer, CSL Behring, Octapharma: Consultancy. Young:Novo Nordisk: Consultancy; CSL Behring: Honoraria.

A survey of the clinical management of pediatric patients with asymptomatic central venous catheter-associated venous thromboembolism in Saudi Arabia

BACKGROUND: Central venous catheters (CVCs) are the main cause of venous thromboembolism (VTE) in critically ill children. The optimal first-line treatment for children with asymptomatic CVC-related VTE is unknown. Due to a paucity of clinical trials, clinical practice guidelines can offer only weak recommendations for the management of asymptomatic CVC-related VTE. METHODS: This case-based survey was designed to assess the current trends in local management strategies for pediatric patients with an asymptomatic CVC-related thrombosis. The survey focused on the use of the thrombophilia testing, management approach, duration of anticoagulation, and the use of secondary prophylaxis. We hypothesize that there will be significant variation in these four management areas, in the large part due to the aforementioned paucity of available data.REDCap® questions were sent to the members of the Saudi Arabian Pediatric Hematology/Oncology Society clinical forum/email database. We used a hypothetical case scenario to assess management strategies for asymptomatic CVC-related VTE and secondary prophylaxis. RESULTS: Seventy-one (30%) physicians responded to the survey. The majority of the respondents (83.3%) did not use thrombophilia testing. The far majority (95%) treated with anticoagulation. In contrast, the survey respondents varied widely in the duration of anticoagulation and the use of secondary prophylaxis. CONCLUSIONS: Asymptomatic CVC-related VTE is a common clinical entity with limited data guiding management. In Saudi Arabia, there remains considerable variability in the clinical management. These findings will help identify crucial knowledge gaps in the management of asymptomatic CVC-related VTE and facilitate clinical trials that will help establish evidence-based treatment guidelines.

The Current Practice of Management of Asymptomatic Central Venous Catheters Associated Venous Thromboembolism in Children: A Result of Saudi Arabian Pediatric Hematology/Oncology Society Survey

Introduction:Central venous catheters (CVCs) are the main cause of venous thromboembolism (VTE) in critically ill children. The optimal first-line treatment for children with asymptomatic CVC-related VTE is unknown. Due to a paucity of clinical trials, clinical practice guidelines can offer only weak recommendations for the management of asymptomatic CVC- related VTE. This case-based survey was designed to assess current trends in local management strategies for pediatric patients with an asymptomatic CVC- related thrombosis. The survey focused on the use of the thrombophilia testing, management approach, duration of anticoagulation, and the use of secondary prophylaxis. We hypothesize that there will be significant variation in these four management areas, in large part due to the aforementioned paucity of available data. Method:After Institutional Review Board approval, REDCap® questions were sent to members of the Saudi Arabian Pediatric Hematology/Oncology Society (SAPHOS) clinical forum/email database. We used a hypothetical case to assess management strategies for asymptomatic CVC-related VTE and secondary prophylaxis. Result:Seventy-one (30%) physicians responded to the survey. The majority of the respondents (83.3%) did not use thrombophilia testing. 95% treated with anticoagulation, of which 20% treated only if clot propagation was identified on follow-up and 3.3% treated only if a thrombophilia was identified. In contrast, the survey respondents varied widely in the duration of anticoagulation (19% for 6 weeks, 41.4% for 12 weeks, 29.3% until CVC removal). Secondary prophylaxis was used by 20% of the respondents, whereas 21.4% did so, only if there was a previously identified thrombophilia. Conclusion:Asymptomatic CVC-related VTE is a common clinical entity with limited data guiding management. In Saudi Arabia there remains considerable variability in clinical management; particularly, in the duration of treatment and use of secondary prophylaxis. These findings will help identify crucial knowledge gaps in the management of asymptomatic CVC-related VTE and facilitate clinical trials that will help establish evidence-based treatment guidelines. Disclosures No relevant conflicts of interest to declare.

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

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. 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 24h 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. There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07vs 0.95 ± 0.21, P=.4), while FVIII (461 ± 120vs 267 ± 130, P=.02), peak thrombin (418 ± 89vs 211 ± 101, P=.001), endogenous thrombin potential (ETP) (1828 ± 485vs 1282 ± 394, P=.03), and velocity index (VI) (182 ± 28vs 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. 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.

Peripherally Inserted Central Catheters Lead to a High Risk of Venous Thromboembolism in Children

Background: The incidence of venous thromboembolism (VTE) in children has seen a sharp increase in recent years with the majority of cases secondary to central venous catheters (CVCs). Among CVCs, the number of peripherally inserted central catheters (PICCs) placed in children has risen significantly. Methods: In this multi-center, prospective, observational cohort study, we enrolled patients aged 6 months to 18 years with newly placed PICCs or tunneled lines (TLs) and compared the incidence of VTE between them. We also evaluated the incidence and risk factors of CVC-related VTE, central line associated bloodstream infections (CLABSIs) and catheter malfunctions in PICCs and TLs. Findings: A total of 1967 CVCs placed in 1742 unique subjects were included in the analysis. The incidence of catheter-related VTE was 5.9±0.63%. The majority of the cases, 80%, were in subjects with PICCs which had a significantly higher risk of catheter-related VTE than subjects with TLs (HR=8.5, 95%CI, 3.1-23, p<0.001). PICCs were also significantly more likely to have a CLABSI (HR=1.6, 95%CI: 1.2-2.2, p=0.002) and CVC malfunction (HR=2.0, 95%CI: 1.6-2.4, p<0.001) compared to TLs. Increased risk of CVC-related VTE was found in patients with a prior history of VTE (HR=23, 95%CI: 4-127, p<0.001), multi-lumen CVC (HR=3.9, 95%CI: 1.8-8.9, p=0.003) and leukemia (HR=3.5, 95%CI: 1.3-9.0, p=0.031). Interpretation: Children with PICCs had a significantly higher incidence of catheter-related VTE, CLABSI and CVC malfunction over TLs. The results suggest that pause be taken prior to placing a CVC, especially PICCs, due to the serious complications they have been shown to cause. Funding Statement: The authors state: there was no funding source for this study. Declaration of Interests: The authors declare that they do not have any conflicts of interest. Ethics Approval Statement: This study was approved by the ethics committee at each participating institution.

Peri-Transplant Venous Thromboembolism in Patients with Multiple Myeloma

Introduction Risk of venous thromboembolism (VTE) is increased in patients (pts) with multiple myeloma (MM) as a result of the biology of the disease and the use of immunomodulatory drugs (IMiDs). These patients frequently undergo autologous hematopoietic cell transplantation (AHCT) transplantation in order to improve disease-free and potentially overall survival. We conducted this study to better understand the incidence and risk factors associated with peri-transplant VTE in this population. Methods 160 MM pts who received IMiD therapy and underwent AHCT between 6/2004 and 11/2016 at our institution were the subjects of this analysis. The peri-transplant period was defined as time from central venous catheter (CVC) insertion up to 60 days post-transplant. None of the pts received VTE prophylaxis during this period. Results All patients received at least one IMiD-based regimen before transplant including thalidomide (31%), lenalidomide (74%), pomalidomide (6%). Imids were stopped at a median of 38 days prior to collection (range 0 days-4 years). CVCs (double lumen n=103, triple lumen n=50, unknown n=7) were inserted a median of 2.5 days prior to mobilized blood collection (range 0-48 days) and were removed a median of 52.5 days after insertion (range 2-303 days). Twenty of 160 patients (12.5%) developed VTE in the peri-transplant period; there was 11 (55%) CVC-related VTE, 6 (30%) lower extremity VTE and 3 (15%) pulmonary embolism. There was no VTE-related death. Median platelet count at the time of VTE was 90 (range, 30-130) x109/L. Eleven VTEs occurred between time of initiation of progenitor cell mobilization and infusion (T-0), and 9 occurred between T-0 and 60 days post-transplant. The rate of catheter-related VTE that occurred before or after T-0 was similar (55%). Thirty-nine percent of pts had a catheter size of less than 14 french; 49% had a catheter size of 14 french or more; the size could not be collected in 12% of the pts. Rate of catheter-related VTE in pts with ≥ 14 and Conclusion In this retrospective single institution analysis, we found a 12.5% incidence of peri-transplant VTEs, which is higher than what was reported in patients receiving transplant for other malignancies [1]. The size of the catheter did not affect the risk of VTE. About half of the VTEs were catheter-related, half of which occurred before T-0. If confirmed on a larger scale, it may be beneficial to give VTE prophylaxis during mobilization to minimize this risk.

Risk-Stratified Anticoagulation Therapy after First Catheter-Related Venous Thromboembolism in Pediatric Patients

Background: The overall incidence of venous thromboembolism (VTE) has steadily increased in the pediatric population, largely due to rising utilization of central venous catheters (CVCs). Anticoagulation is the mainstay therapy for pediatric CVC-related VTE. Due to paucity of prospective data, optimal duration of anticoagulation therapy has yet to be defined and current recommendations for anticoagulation duration are largely extrapolated from data in adult patients with lower extremity deep vein thrombosis (DVT) and small, non-randomized studies. The objective of this study is to report outcomes of a risk-stratified anticoagulation protocol in a cohort of pediatric patients with CVC-related VTE followed at our center.Methods: We performed a retrospective analysis of a prospectively maintained institutional thrombosis patient registry created using Research Electronic Data Capture (REDCap). We identified all patients with an objectively confirmed catheter-related VTE who were followed at our institution over a 5-year period (2012-2017). Patients were managed according to an institutional risk-stratified protocol in which patients received therapeutic enoxaparin for a maximal duration of 3 months with assessment of radiologic response at 6 weeks and 3 months. After 6 weeks of therapy, enoxaparin was discontinued if the CVC had been removed, or decreased to prophylactic dosing if the CVC is still present in low risk patients with non-recurrent CVC-related DVT who had complete radiologic thrombus resolution and no major thrombophilia. We compared patients with complete resolution at 6 weeks to those who did not have complete resolution at 6 weeks with respect to demographics, relevant clinical characteristics, baseline laboratory measurements, anticoagulation quality measurements, and key outcome measures (frequency of a composite of recurrent symptomatic radiologically-confirmed DVT, pulmonary embolism (PE) and/or paradoxical embolism, frequency of post-thrombotic syndrome (PTS), and frequency of anticoagulation-related major bleeding and/or clinically relevant non-major bleeding). Data was compared using the Mann-Whitney U test or Fisher exact test as appropriate. Two-tailed p value less than 0.05 was considered statistically significant.Results: A total of 137 patients who developed a CVC-related VTE at our institution during the study period were included in the analysis. Of 137 patients, 70 (51%) patients had complete radiologic resolution at 6 weeks, while 26% had partial resolution, 20% had non-resolution and 3% were noted to have radiologic progression. At 3 months, 38% of patients had complete resolution, 24% had partial resolution, 21% had non-resolution and 7% showed radiologic progression. Patients who had complete resolution at 6 weeks were largely similar in their characteristics to those who did not show complete resolution at 6 weeks (Table 1). The frequency of thrombophilia was not different between the two groups and none of the patients were found to have major thrombophilia (Table 1). However, the frequency of vena cava involvement was significantly higher and the time to achieve therapeutic anticoagulation was significantly longer in patients who did not show complete resolution at 6 weeks (Table 1). The frequency of recurrent clinically symptomatic DVT, PE and/or paradoxical embolism in patients with complete radiologic resolution at 6 weeks [5/70 (7%)] was similar to those who did not show complete radiologic resolution at 6 weeks [9/67 (13%)] (p=0.27). The frequency of PTS was significantly higher in patients who did not show complete radiologic resolution at 6 weeks [5/60 (8%)] compared to patients with complete radiologic resolution at 6 weeks [0/64 (0%)] (p=0.02). The frequency of anticoagulation-related bleeding events was similar in patients with complete radiologic resolution at 6 weeks [6/70 (9%)] and patients who did not have complete radiologic resolution at 6 weeks [6/67 (9%)] (p=1.00).Conclusion: Our study suggests that pediatric patients with CVC-related DVT who demonstrate complete radiologic resolution after 6 weeks of anticoagulation represent a lower risk patient group that appears to have favorable outcomes. Vena cava involvement and longer time to achieve therapeutic anticoagulation may be associated with suboptimal radiologic response at 6 weeks. Larger prospective studies are needed to confirm our results. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Central Venous Catheter-associated Venous Thromboembolism in Children With Hematologic Malignancy.

In pediatric oncology, the diagnosis of a hematologic malignancy and presence of a central venous catheter (CVC) have been identified as significant risk factors for the development of a venous thromboembolism (VTE). There remain little data regarding CVC factors associated with CVC-related VTE. Using the VTE and oncology database in a quaternary care center, a retrospective cohort study was conducted in children below 18 years old with hematologic cancer from November 5, 2012 to April 4, 2016. Patient, CVC factors, and VTE occurrence were analyzed to identify significant patient and CVC factors associated with the development of clinically identified CVC-related VTE. Utilizing the χ, Mann-Whitney, and the Fisher exact tests, patient factors were compared across VTE yes/no groups. Of the 198 study patients, 22 VTE cases were identified. Eighteen VTE events were CVC-associated, occurring in 9% of study population. Peripherally inserted central catheter lines and older ages were associated with VTE. The use of tissue-plasminogen activator for CVC occlusion was associated with decreased VTE rates, suggesting a protective potential.

Six Weeks Versus 3 Months of Anticoagulant Treatment for Pediatric Central Venous Catheter-related Venous Thromboembolism.

Central venous catheters (CVCs) are the single most important predisposing factor for the development of pediatric venous thromboembolism (VTE). Treatment recommendations suggest anticoagulation for the duration of 6 weeks to 3 months. This project investigated clinical outcomes associated with 6 weeks compared with 3 months of enoxaparin therapy following diagnosis of a CVC-related VTE. This retrospective cohort study enrolled patients aged 18 years and below treated with enoxaparin with/without unfractionated heparin for a radiologically confirmed CVC-related VTE. Patients were identified using the pharmacy database, radiologic imaging, and medical records. Patients were divided into 2 groups based on the duration of anticoagulation (6+1 or 12±2 wk) and data were analyzed using descriptive statistics. Seventy-four patients were included. Higher rates of complete thrombosis resolution were observed in children treated for 6 weeks at treatment cessation (39.4%) and long-term follow-up (61.5%), compared with 3 months (11.8% and 9.0%, respectively). Six weeks of treatment for CVC-related VTE may provide noninferior clinical outcomes compared with 3 months of anticoagulation. An international randomized-controlled trial (Kids-DOTT) is underway to explore the optimal duration of anticoagulation for acute-provoked VTE in children. This manuscript highlights that data from such studies is urgently needed.

Determining the Incidence and Risk Factors for Central Venous Catheter Related Thrombosis in Children

Introduction: Venous thromboembolism (VTE) rates in children are increasing, largely due to the improved care of critically ill children and the placement of central venous catheters (CVCs). There is limited evidence regarding risk factors for CVC-associated thrombosis, and there are no guidelines for pediatric patients on choosing catheter type, insertion technique or consideration for prophylaxis. This study aims to be the first prospective, observational, multi-center, pediatric study to compare the VTE incidence between peripherally inserted central catheters (PICCs) and centrally inserted tunneled lines (TLs), as well as identify additional risk factors for CVC-associated thrombosis.Methods: This prospective, observational cohort study enrolled patients aged 6 months to <18 years from 3 large pediatric hospitals, Children’s Hospital Los Angeles, Children’s Hospital of Philadelphia and Texas Children’s Hospital between September 2013 to April 2016 who either had a PICC or TL placed. Data regarding subject demographics and medical history (cancer, congenital heart disease, history of VTE, current infection, etc.) were collected via electronic medical record (EMR) review. Details specific to the CVC (reason for insertion, CVC size, number of lumens, brand and CVC material) and insertion technique (length of CVC, vein accessed, number of attempts) were also collected. Subjects were then prospectively monitored for the occurrence of a VTE and other CVC-related complications (infection, malfunction, use of tissue plasminogen activator) via EMR review for up to 6 months after their CVC was placed or after diagnosis of a VTE. Univariable and multivariable logistic regression was utilized to examine the association of patient and CVC characteristics on VTE incidence. All significant predictors (p < 0.10) in the univariable analyses were entered into a multivariable model where each predictor’s contribution was assessed.Results: Interim analysis includes 789 subjects [53% male, median age 6 years (0.5, 18)] who had 883 CVCs placed (Table 1). PICCs were placed in 570 (65%) subjects and 313 (35%) had TLs placed. There were a total of 43 CVC-related VTEs (4.9%) and the majority, 37 (86%), were in subjects with PICCs. The median time to develop a PICC-associated VTE after placement was 37 days (1, 215). Twenty-four predictors were analyzed in separate logistic regression models. Univariable analysis of twenty-four possible predictors revealed a statistically significant increased risk of VTE incidence in subjects with a history of VTE with an odds ratio (OR) of 2.9 [95% confidence interval (CI), 1.3-6.6] or congenital heart disease OR=2.8 (CI 1.3-6.0), subjects with PICCs (vs. TLs) OR=3.8 (CI 1.6-9.1), multiple lumen CVCs (TL or PICC) OR=3.2 (CI 1.7-6.0) or in CVCs with a malfunction OR=2.1 (1.1-3.9). Male gender, on the other hand, was associated with a reduced risk of VTE OR=0.46 (0.2-0.9). Type of CVC (PICC vs. TL) OR=3.4 (CI 1.4-8.2), number of lumens OR=2.7 (CI 1.5-5.3), and history of VTE OR=2.8 (CI 1.2-6.5) remained significant positive predictors of VTE incidence in the setting of a multivariable model. Male gender remained to be inversely associated with VTE incidence (Table 2).Conclusions: This is the first prospective pediatric study comparing VTE incidence in PICCs versus TLs. This interim analysis of nearly 800 subjects revealed a significantly higher risk of VTE in subjects who have had a PICC placed versus a TL. Due to their ease of insertion, PICCs are being placed at increasing rates in some pediatric centers, thus this finding may be the leading factor for the increasing pediatric VTE incidence. Other significant risk factors for VTE were patients with multiple lumen CVCs and a history of VTE. For children who require a new CVC, practitioners should consider avoiding PICCs and multiple lumen CVCs if possible. Consideration should also be made to give prophylactic anticoagulation for children with a CVC and a history of VTE. Further analysis will be performed concerning the decreased VTE rate in male patients.The identification of these risk factors is the first step to creating CVC selection and insertion guidelines for all children to prevent VTE. Continued subject recruitment, with the recent addition of Nationwide Children's Hospital, is occurring to complete this evaluation. [Display omitted] [Display omitted] DisclosuresYoung:Biogen: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Kedrion: Consultancy; Baxter: Consultancy.

A shortened activated partial thromboplastin time predicts the risk of catheter-associated venous thrombosis in cancer patients

IntroductionHypercoagulability due to high coagulation factor levels resulting from host inflammatory response to cancer contributes to an increased risk of venous thromboembolism (VTE) in cancer patients. Central venous catheters (CVCs) further heighten this risk. Activated partial thromboplastin time (aPTT) can be used to broadly screen for elevated levels of relevant coagulation factors. Our objective was to determine if a shortened aPTT ratio (coagulation time of test- to- reference plasma) was a predictor of CVC-associated VTE in cancer patients. Materials and MethodsWe performed a retrospective case–control study on cancer patients undergoing tunneled CVC insertion at our center from 1999 to 2006 and identified 40 patients who had CVC-associated VTE. VTE was confirmed with color duplex ultrasonography or computed tomography scan. For each case, we obtained 5 controls that had the same cancer diagnosis and were matched on the following factors: age, chemotherapy, hormone therapy (if applicable), tobacco use, TNM staging and year of diagnosis. All patients had aPTT testing within 30days prior to surgery. We compared aPTT and aPTT ratio between cases and controls using Wilcoxon two sample test. ResultsaPTT ratio was significantly shorter in patients with CVC-related VTE as compared to controls [0.86 (95% confidence interval (CI) 0.78, 0.94) vs. 0.98 (0.94, 1.01), p=0.0003]. Mean aPTT was also significantly shorter. [25.6seconds (95% CI 23.2, 27.9) vs. 28.1 (26.9, 29.3), p=0.001] aPTT ratios of the controls tended to spread across larger aPTT ratio values whereas those of cases tended to clustered around the mean. ConclusionsCancer patients undergoing catheter placement who develop CVC-associated VTE have a shorter aPTT and aPTT ratio than those who do not develop VTE. aPTT, a simple and inexpensive test might be useful as a predictor of CVC-associated VTE risk in cancer patients.

Hospital-Associated Venous Thromboembolism in Children: Incidence and Clinical Characteristics

To determine incidence and clinical characteristics of hospital-associated venous thromboembolism (VTE) in pediatric patients. A retrospective analysis of patients with hospital-associated VTE at the Johns Hopkins Hospital from 1994 to 2009 was performed. Clinical characteristics of patients aged 21 years and younger who developed VTE symptoms after 2 days of hospitalization or <90 days after hospital discharge were examined. International Classification of Diseases, Ninth Revision codes were used to categorize patients with complex chronic medical conditions and trauma. There were 270 episodes of hospital-associated VTE in 90,485 admissions (rate 30 per 10,000 admissions). Young adults (18-21 years) and adolescents (14-17 years) had significantly increased rates of VTE compared with children (2-9 years) (incidence rate ratio [IRR] 7.7, 95% CI 5.1-12.0; IRR 4.3, 95% CI 2.7-6.8, respectively). A central venous catheter (CVC) was present in 50% of patients, and a surgical procedure was performed in 45% of patients before VTE diagnosis. For patients without a CVC, trauma was the most common admitting diagnosis. CVC-related VTE was diagnosed most frequently in infants (<1 year old) and in patients with malignancy. Renal and cardiac diseases were associated with the highest rates of VTE (51 and 48 per 10,000, respectively). Rates were significantly higher among those with ≥ 4 medical conditions compared with those with 1 medical condition (IRR 4.0, 95% CI 1.4-8.9). Older age and multiple medical conditions were associated with increased rates of hospital-associated VTE. These data can contribute to the design of future clinical trials to prevent hospital-associated VTE in high-risk children.

Enoxaparin for the Prevention of Venous Thromboembolism Associated With Central Vein Catheter: A Double-Blind, Placebo-Controlled, Randomized Study in Cancer Patients

The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.

Swimming and central venous catheter-related infections in the child with cancer

Hypercoagulability due to high coagulation factor levels resulting from host inflammatory response to cancer contributes to an increased risk of venous thromboembolism (VTE) in cancer patients. Central venous catheters (CVCs) further heighten this risk. Activated partial thromboplastin time (aPTT) can be used to broadly screen for elevated levels of relevant coagulation factors. Our objective was to determine if a shortened aPTT ratio (coagulation time of test- to- reference plasma) was a predictor of CVC-associated VTE in cancer patients.We performed a retrospective case–control study on cancer patients undergoing tunneled CVC insertion at our center from 1999 to 2006 and identified 40 patients who had CVC-associated VTE. VTE was confirmed with color duplex ultrasonography or computed tomography scan. For each case, we obtained 5 controls that had the same cancer diagnosis and were matched on the following factors: age, chemotherapy, hormone therapy (if applicable), tobacco use, TNM staging and year of diagnosis. All patients had aPTT testing within 30 days prior to surgery. We compared aPTT and aPTT ratio between cases and controls using Wilcoxon two sample test.aPTT ratio was significantly shorter in patients with CVC-related VTE as compared to controls [0.86 (95% confidence interval (CI) 0.78, 0.94) vs. 0.98 (0.94, 1.01), p = 0.0003]. Mean aPTT was also significantly shorter. [25.6 seconds (95% CI 23.2, 27.9) vs. 28.1 (26.9, 29.3), p = 0.001] aPTT ratios of the controls tended to spread across larger aPTT ratio values whereas those of cases tended to clustered around the mean.Cancer patients undergoing catheter placement who develop CVC-associated VTE have a shorter aPTT and aPTT ratio than those who do not develop VTE. aPTT, a simple and inexpensive test might be useful as a predictor of CVC-associated VTE risk in cancer patients.