Presence Of Central Venous Line Research Articles

Antifungal Resistance and Breakthrough Candidemia Among Pediatric Cancer Patients: An Emerging Threat

Abstract Background Cancer patients are at risk for candidemia. Resistance and breakthrough Candida represent an emerging threat. The study aims to analyze the clinical features, resistance patterns and breakthrough candidemia among pediatric cancer patients. Methods The retrospective study was conducted from 2014 - 2020 in children admitted to Children Cancer Hospital, Egypt. Clinical, microbiological, and outcomes were analyzed. Mortality was estimated within 30 days from Candida spp. Isolation from blood. Results Three hundred fifty (350) pediatric cancer patients were diagnosed with candidemia. The median age was four years (4 months- 18 years). Most of the patients had hematological malignancies (54%) while solid tumors represent (46%). Clinical features of the patients included neutropenia (80%), the presence of central venous line (57%), ICU admission (44%), and steroid use (43%). Non-Albicans candida was predominant (71%) compared to Candida Albicans (29%). The isolated species were: C. Albicans (29%), C.Tropicalis (29%), C. parapsilosis (21%), C. krusei (7%), C.glabrata(3%), C. guilliermondii (1.5%)and C. famata (2%). Chronic disseminated candidiasis was reported in 30 (9%) patients, with the liver being the most affected organ. Breakthrough candidemia on top of echinocandin prophylaxis was reported among 62(18%) patients with C. parapsilosis is the most common 31(50%) isolated pathogen. From 96 patients with breakthrough candidemia, all-cause mortality was reported in 32 patient (33%) while candida attributable cause of death in elven (11%) patients. Antifungal resistance was reported in 74(21%) patients: fluconazole (15%), liposomal ampho-B (6%), echinocandin (5%) and voriconazole (3%). Among 74 patients with resistant candidemia, death was reported in 24%. Echinocandin Resistant candida was a direct cause of mortality in 3(17%) patients. The overall day- 30 mortality rate was 24% (85/350 patients), while candida attributable of mortality was (10%). Patients with septic shock, ICU admission, and resistant candida had a higher mortality risk. Conclusion Echinocandin-resistant and breakthrough Candida are significant threat with a high mortality rate among pediatric cancer patients. Antifungal stewardship may be helpful. Figure 1. Resistance Pattern of Candidemia among Pediatric Cancer Patients

Elevated International Normalized Ratio (INR) Did Not Prevent Against Thrombosis in Patients with Chronic Liver Disease (CLD): A Population Based Study

Background: Elevated INR values are common among patients with chronic liver disease (CLD), and signify a decrease in the synthesis of clotting factors II, V, VII, IX and X. Preclinical evidence suggests that the decrease in these factors is balanced by a decrease in anticoagulant factors (e.g. antithrombin, protein C) and an increase in factor VIII {Tripodi 2009, Tipodi 2010}, establishing a rebalanced hemostasis in CLD {Tripodi 2011}. The proposed rebalanced hemostasis has been observed in vitro by rate of thrombin generation being similar to that of individuals with normal hepatic function {Tripodi 2005, Tripodi 2006}. There is however, a lack of in vivo data supporting rebalanced hemostasis in CLD patients. Whether an elevated INR protects against thrombosis among these patients is therefore controversial. We studied the INR-specific rate of non-portal venous thromboembolism (VTE) in a large cohort of United States Veterans with CLD. Methods: Study Population: We identified patients diagnosed with CLD in the Veterans Health Administration database between January 2001 and December 2016 using International Classification of Diseases (ICD) 9/10 codes. To improve the positive predictive value of CLD diagnosis, we followed a previously validated algorithm where patients were required to have an additional ICD9/10 code for one of the common clinical presentations of CLD (e.g., esophageal varices). We identified a control cohort of patients with atrial fibrillation using ICD9/10 codes that had a prescription for warfarin for at least 30 days. Patients with artificial valves, history of VTE within 5 years prior to diagnosis and malignancy were excluded from both cohorts. Patients on warfarin were excluded from the CLD cohort, and those on other anticoagulants were excluded from the control cohort unless anticoagulation was started after a thrombotic event. Patients were followed retrospectively until December 2016. Measurement of Outcomes: Non-portal VTE was identified using ICD9/10 codes plus the presence of a current procedural terminology code for relevant diagnostic imaging (e.g. Doppler ultrasound or computerized tomography scan). Statistical Analysis: To account for the competing risk of non-VTE related death, we analyzed the association between INR and non-portal VTE in a competing risk analysis by the methods of Fine and Gray. For atrial fibrillation patients with newly prescribed warfarin, time 0 started 15-days after their 1st warfarin prescription. For patients with CLD, time 0 was the time of first INR measurement, at least 15 days after CLD diagnosis. We used the natural logarithm of INR as a time-dependent continuous variable in the analysis, and adjusted for the following confounders: age, gender, race, body mass index (BMI), concomitant antiplatelet therapy, surgery, fracture, trauma, presence of central venous line, estimated glomerular filtration rate (GFR), and Charlson comorbidity index (excluding liver disease and chronic kidney disease). The primary test of our hypothesis (that INR values had a different risk among patients with CLD than warfarin users) was an interaction term between CLD (Yes/No) and INR. Results: A total of 15,930 patients with CLD, and 81,415 atrial fibrillation patients on warfarin were included in the study. During the 12-month follow-up, 164 CLD patients and 1,347 warfarin users developed VTE. African American race, low serum albumin, low eGFR, central-line placement, surgery, fracture and trauma increased the risk of VTE. The interaction between INR and CLD was significant (p < 0.01) i.e., the effect of INR values on the incidence of VTE differed between CLD patients and warfarin users. Each unit-increase in INR decreased the risk of VTE in warfarin users by 33% [adjusted hazards ratio (aHR)= 0.67 , 95% Confidence Interval (CI)=0.56 to 0.80]); it however, did not affect the risk of VTE in CLD patients (aHR=1.45, 95% CI=0.82 to 2.59) Conclusion: In this study of 97,345 Veterans, elevated INR values did not decrease the risk of VTE in CLD patients. Thus, healthcare providers should not rely solely on INR values to inform decisions regarding primary and secondary thromboprophylaxis in this patient population. Disclosures Sanfilippo: Bayer HealthCare Pharamceuticals: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Other: Travel Support for Investigator Meeting; Pfizer: Membership on an entity's Board of Directors or advisory committees; Covington & Burling LLP: Consultancy; Luther & Associates: Consultancy; Health Services Advisory Group: Consultancy; Amgen: Other: Trasfer of Value (food) during discussion of research.

Cancer-associated thrombosis in pediatric patients

Childhood malignancy and especially acute lymphoblastic leukemia are increasingly associated with thromboembolism. The etiology of pediatric cancer associated thrombosis is multifactorial and may reflect a tumor mass effect, tumor thrombi, alterations of the hemostatic system, treatment-related hazards (e.g. procoagulant changes induced by chemotherapy), presence of central venous lines and comorbidities (e.g. inherited thrombophilia). With over 80% cure rates of childhood cancer, strategies for prevention as well as for early diagnosis and optimal treatment of thromboembolism in children with malignancies are of major importance. While the use of therapeutic low molecular weight heparin prevails, prospective studies regarding guidelines for treatment or prevention are currently lacking. This review will address the epidemiology, etiology and risk factors for thrombosis, describe the presently available evidence associated with current therapy, and offer a glimpse into future treatment options.

Herding CATs? The Incidence and Prevention of Catheter-Associated Thromboses (CATs) in Pediatric Patients after Cardiac Transplant

The presence of central venous lines (CVLs) post cardiac transplant increases the risk of catheter-associated thromboses (CATs) impacting vascular access. CATs also contribute to the need for prolonged anticoagulation increasing the risk of bleeding and diminished quality of life. Little data exists quantifying the incidence of CATs or associated risk factors after cardiac transplantation in pediatric patients. We aimed to study the incidence of CATs and the impact of a risk-stratified anticoagulation protocol in reducing their development. This is a single-center, retrospective review of patients less than 18 years of age with CVLs after cardiac transplantation from 2009-2018. Data collected included demographic data, CVL location, thrombosis data, anticoagulant use, and adverse events. Patients were started on an anticoagulation (AC) protocol (see Table 1) after 2016 and were compared to pre-protocol patients. CATs were noted in 39 (42%) of 93 patients analyzed. Eight (8.6%) patients experienced major bleeding which was associated with older age (p=0.021) and history of congenital heart defect (p=0.067). There were 76 patients prior to AC protocol implementation compared to 17 post-protocol. Preliminary analyses showed no difference in the rate of CATs (42.1% vs. 41.2%, p=0.54); however, of clots that developed after implementation, there were significantly fewer occlusive thromboses (15.8% vs. 35.3%, p=0.05) decreasing the need for further anticoagulation by 13.3%. This study highlights the significant risk of CATs after heart transplantation in pediatric patients. In an attempt to decrease the rate of CATs, a risk-stratified AC protocol was developed and implemented. Though initial data is limited, patients who received early post-operative anticoagulation after transplant had less severe CATs and decreased need for therapy after line removal.

The association of mediastinal mass in the formation of thrombi in pediatric patients with non-lymphoblastic lymphomas.

Children diagnosed with cancer are at a significantly higher risk of developing a thrombotic event (TE) compared with the general population. The rarity of these events makes it difficult to discern the specific risk factors; however, age, sex, presence of central venous lines, inherited thrombophilia, and mediastinal mass may play a role. The primary aim of this study is to identify prognostic characteristics of children diagnosed with non-lymphoblastic lymphomas associated with a greater risk of developing a TE early on in their disease, with an increased focus on mediastinal mass characteristics. Retrospective chart review of pediatric patients diagnosed with non-lymphoblastic lymphoma between 2004 and 2014 at St. Jude Children's Research Hospital. TE occurred in 8.5% (n=28/330) of individuals at a median of 21 days from the diagnosis of a non-lymphoblastic lymphoma, with 60% of TEs occurring within 30 days of diagnosis. Of the variables evaluated, only presence of a peripherally inserted central catheter (odds ratio [OR]: 3.14 [95% CI: 1.24-7.98; P=0.02]) and degree of superior vena cava (SVC) compression of>25% increased the odds of developing a TE (OR: 2.2 [95% CI: 1.01-4.93; P=0.048]). Pediatric patients with non-lymphoblastic lymphoma are at increased risk of developing TEs. In contrast to previous studies, the presence of a mediastinal mass alone was not associated with a higher risk of TE, but individuals with a mediastinal mass with 25% or greater degree of SVC compression were more likely to develop a TE. This finding highlights a high-risk group of children who may benefit from prophylactic anticoagulation.

A Retrospective Review of Hospital-Acquired Venous Thromboembolism at a Large Pediatric Tertiary Care Center

Introduction: The incidence of venous thromboembolism (VTE) in hospitalized pediatric patients is increasing secondary to the growing medical complexity of pediatric patients and the increasing use of central venous catheters. Pediatric patients diagnosed with VTE have up to 2% mortality associated directly with their thromboses. While incidence, risk factor identification and preventive strategies are well established in hospitalized adults, this information is limited in the pediatric population. There are currently no standardized VTE risk screening tools or thromboprophylaxis guidelines for children at Duke Children's Hospital. The incidence of hospital acquired VTE (HA-VTE), as well as their associated risk factors were investigated in a retrospective review. Methods: Medical records of pediatric patients hospitalized at Duke Children's Hospital during June 2018 through November 2018 were reviewed. The EPIC SlicerDicer tool was used to identify patients with ICD-10 diagnoses codes related to thrombosis or treated with anticoagulants. Included patients were diagnosed with HA-VTE during their hospitalization or within 14 days of discharge. Data collected included demographics, thrombosis characteristics, family history, mobility, and acute or chronic co-morbid conditions. The characteristics of the study population were described by median (with 25th and 75th percentiles) for continuous variables and frequencies (with percentages) for binary or categorical variables. Results: Out of 4,176 total pediatric admissions to all units of Duke Children's Hospital (ages 0-18.99 years) during the inclusion timeframe, 33 VTE events were identified. The incidence of VTE events per 1000 patient days was 0.98. The complete patient and VTE event characteristics are listed in Tables 1 and 2. The median age of patients with VTE events was 0.4 years. Of the identified cohort, 73% had an associated central venous line (CVL). Neonates with congenital cardiac disease comprised the majority of the cohort. Other common patient characteristics observed in this cohort included impaired mobility, recent major surgery, and recent mechanical ventilation. Of the 33 VTE diagnoses, 70% received therapeutic anticoagulation with enoxaparin or unfractionated heparin. Only 2 patients (8%) received prophylactic anticoagulation prior to their diagnosis of VTE. Conclusions: The retrospective review of HA-VTE events at Duke Children's Hospital identified that the majority of the events occurred in neonates with congenital cardiac disease and the presence of CVLs. It was also noted that there was no standardization among the use of anticoagulation agents that were initiated for treatment of VTE. Furthermore, few patients received VTE prophylaxis during the hospitalization. A limitation of this review was that it was retrospective and the documentation of family history of thrombosis was inconsistent. It is also possible that several VTE events were missed due to inadequate ICD-10 coding. Based on the results of this review, there is a need to implement a risk stratification tool and develop standardized recommendations of VTE prophylaxis and treatments for pediatric patients admitted to Duke Children's Hospital. There is an additional quality improvement phase of this project and the goal is to implement a risk calculator that is based on information learned from the retrospective review. Ultimately, this risk calculator will help to decrease the incidence of VTE events at Duke Children's Hospital. Disclosures Rothman: Agios: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

To study the profile of Candida isolates and antifungal susceptibility pattern of neonatal sepsis in a tertiary care hospital of North India

Aims and objective To study the profile of Candida infection and antifungal susceptibility (AFS) pattern in neonatal sepsis. Materials and methods In this prospective observational study, 850 blood samples were collected and processed from neonates who were suspected clinically to have sepsis. The blood culture that showed growth of Candida was further processed for species identification. Antifungal susceptibility was done as per the National Committee for Clinical Laboratory Standards (NCCLS)/Clinical Laboratory Standards Institute (CLSI) M44-A-2 guidelines by disc diffusion method and automated vitek-2 compact system. Candidemia was diagnosed by isolation of Candida species from at least one positive blood culture containing pure growth of Candida species with supportive clinical features. Results Candida species were isolated in 32 specimens of the total 322 culture-positive cases. The most common isolate was Candida tropicalis (14/32; 43.75%) followed by Candida albicans (7/32; 21.87%) and Candida glabrata (6/32; 18.75%). The three most common neonatal risk factors for candidemia were low birth weight, prolonged use of intravenous antibiotics and presence of central venous line. Non-albicans Candida (NAC) showed good sensitivity to fluconazole as compared to Candida albicans. The fluconazole sensitivity of Candida tropicalis, Candida glabrata, and Candida parapsilosis was 93, 67, and 100%, respectively, whereas it was 57% in Candida albicans. The sensitivity to amphotericin B was 95% among all Candida isolates. All NAC were sensitive to amphotericin B, while only 72% Candida albicans were sensitive to amphotericin B. Conclusions The incidence of neonatal sepsis secondary to NAC is increasing and has replaced Candida albicans as a major cause of neonatal fungal sepsis. Low birth weight is the most important risk factor for Candida sepsis. The resistance of Candida albicans is increasing for both fluconazole and amphotericin B when compared to NAC. Increasing antifungal resistance warrants its judicious use both for prophylaxis and treatment.

Central Venous Line Associated Deep Vein Thrombosis in Hospitalized Children.

An increase in the incidence of deep vein thrombosis (DVT) has been reported in pediatric patients over the past decade. The presence of central venous line (CVL) is a major contributing risk factor with conflicting data on the relative risk of DVT with various types of central lines. We aimed to assess the incidence of and identify potential risk factors for DVT overall and with different types of CVL individually. A retrospective chart review of pediatric patients with a CVL placed at Cleveland Clinic Children's from 2011 to 2016 was conducted. Data collected included demographics, potential risk factors, CVL characteristics and related thrombotic events. The study cohort consisted of 376 CVLs in 325 patients between 0 and 26 years of age. There were 1.6 thrombi per 10,000 line-days (95% confidence interval: 1.0, 2.5), and the overall incidence of DVT was 5.1%. The incidence of DVT was highest with tunneled catheters (5/16=31%) versus with peripherally inserted central catheters (4/111=3.6%) or with ports (10/249=4%, P<0.001), and whereas there were overarching significant risk factors for CVL-associated thrombi, these risk factors differed in significance when analyzed by the CVL type. The study supports the need for continued improvement in pediatric hospital practices for early identification of patients at a higher thrombosis risk.

Utility of follow-up blood cultures for Gram-negative rod bacteremia in children

Persistent Gram-negative rod (GNR) bacteremia is uncommon under appropriate antibiotic therapy. A recent study showed that follow-up blood cultures (FUBCs) to confirm clearance 24–48 h after initiation of antibiotics, added little value in the management of GNR bacteremia in adults. However, the utility of FUBC in children is still unknown. We retrospectively reviewed the microbiology database to identify children aged <18 years with GNR bacteremia. Clinical information including gender, age, underlying diseases, presence of central venous line (CVC), source of bacteremia, and organisms was extracted from medical records. FUBCs for 99 episodes of GNR bacteremia in children became positive in 21%, which led to intervention in 57% of the episodes. In multivariate analysis between FUBC positive (n = 21) and negative (n = 78) groups, presence of CVC (n = 18, 86% vs n = 38, 49%, P = 0.001) and resistance to empirical antibiotics (n = 3, 14% vs n = 4, 5%, P = 0.04) were independently associated with positive FUBCs. Interestingly, no positive FUBC was observed in cases due to UTI (n = 13). Contrary to findings in adults, FUBC may still be useful in the management of GNR bacteremia in children.

Thrombosis in pediatric patients with leukemia

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. It is reportedly the most common malignancy associated with thromboembolism in the pediatric age group. Over the last 2 decades, venous thromboembolism (VTE) has been increasingly diagnosed among pediatric ALL patients with an estimated incidence ranging from about 5% (for symptomatic cases) to about 30–70% (following sequential imaging studies in asymptomatic children). The etiology is multifactorial and may stem from alterations of the hemostatic system following various chemotherapy protocols (including use of l-Asparaginase), the presence of central venous lines (CVL), as well as comorbidities, e.g. inherited thrombophilia risk factors. Most symptomatic thrombotic events occur in the upper venous system or in the central nervous system (CNS). Prospective studies on the establishment of guidelines for treatment or prevention are lacking. The following review will address the epidemiology, etiology and risk factors for thrombosis, describe the currently available evidence, and address issues associated with diagnosis and treatment.

BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy.

BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy.

Microbial epidemiology of candidaemia in neonatal and paediatric intensive care units at the Children's Medical Center, Tehran.

Invasive candidiasis is a major cause of morbidity and mortality in children. However, limited data are available on the epidemiology of this infection in paediatric settings in Iran. The aim of this study was to determine the prevalence, microbial epidemiology, risk factors and clinical outcomes associated with candidaemia in intensive care units at the Children's Medical Center, Tehran, Iran. All blood and other normally sterile specimen cultures positive for Candida species were included. Isolates were identified by morphological and molecular methods. Unidentified/doubtful yeast isolates were subjected to ITS sequencing. A total of 156 episodes of invasive candidiasis, with an overall incidence of 15.2 per 1000 ICU admissions, was recorded. Risk factors included presence of central venous lines (89.1%), mechanical ventilation (55.8%) and parenteral nutrition (51.3%). Candida albicans (57.1%) and Candida parapsilosis (24.4%) were the most commonly isolated species. Candida orthopsilosis, Candida glabrata, Candida dubliniensis, Candida lusitaniae, Candida kefyr and Candida intermedia accounted for about 11% of the cases. The overall mortality rate was 42.5%. Non-albicans Candida species accounted for nearly half of the cases of paediatric candidaemia. This is the first prospective study of candidaemia in paediatric settings in Iran and serves to inform necessary interventions for the prevention of candidaemia.

Thrombin Generation and Microparticles As Promising Biomarkers for Venous Thromboembolism in Children with Central Venous Lines

Background: Pediatric hospital-acquired venous thromboembolism (HA-VTE) has increased over the past ten years (Raffini et al. Pediatrics 2009; 124; 1001-1008), with an associated increase in both VTE-associated complications and treatment-related adverse events. Children with VTE have a four-fold increase in length of admission compared to children without VTE. There are many known clinical risk factors but the presence of central venous lines (CVLs) has been shown to be among the strongest risk factors in children (Mahajerin et al. Haematologica 2015 Aug; 100(8): 1045-50). Current tools, including clinical risk-prediction scoring systems as well as genetic risk factors, are not sufficient to predict VTE risk at this time. Identification of dependable, rapid and cost-effective biomarkers for the prediction of VTE in children with CVLs is essential in guiding anti-coagulation prophylaxis, thus reducing VTE occurrence among hospitalized children with CVLs.Objectives: Determine the ability of thrombin generation (TG) and microparticle-based phospholipid-dependent procoagulant potential (MP-PPL) to predict VTE occurrence in hospitalized children with CVLs.Methods: Plasma sample were collected from 34 hospitalized acutely ill children between the age of 1 month and 21 years, who are at risk for VTE due to multiple known clinical risk factors, including a newly placed non-tunneled CVL. Children that had undergone a recent cardiac catheterization or on dialysis, plasmapheresis or ECMO were excluded. Samples from 16 age matched healthy controls were also collected. Venous samples were collected prior to CVL placement. Platelet poor plasma (PPP) was obtained according to a strict protocol to minimize pre-analytical variable. All pertinent clinical and laboratory information was extracted, including CVL-related variables and details of VTE in affected subjects. TG was measured by means of the calibrated automated thrombogram (CAT). MP-PPL was measured using two methods: 1) Functional assay that detects the ability of circulating MPs to indirectly facilitate thrombin generation (Zymuphen MP-Activity kit, Hyphen BioMed, France), 2) Clot-based assay that measures phospholipid-dependent, factor Xa initiated clotting time in relation to normal controls (STA-Procoag-PPL, Diagnostica Stago).Results: The median age of our cohort was 10 yrs (IQR 12, range 0 - 19), with a slight male predominance (53%) and increased representation of adolescents (41%). CVLs were placed in an intensive care setting in 38% of subjects and 39% of subjects had an underlying condition associated with chronic inflammation. The median duration of CVL placement from admission was 2 days (IQR 5, range 1 - 19) and the median total duration of CVLs were 14 days (IQR 20, range 5 - 84). Line-associated VTE occurred in 9% (3/34) of children with CVL and one subject had a VTE unrelated to CVL. There was no observed significant difference between children with or without line-related VTE in terms of age, gender, lag of CVL placement from admission, duration of CVLs, caliber of initial vessel of insertion, number of lumens, size of CVL and internal length of the CVL. However, all subjects with line-associated VTE were admitted for acute infection to an intensive care setting, with the majority of VTE occurring within 48 hours from line placement (2/3). Correlation analysis of the two MP-PPL assays was significant (r = -0.659). Even though the MP-PPL functional assay did not show a significant difference between subjects with and without line-associated VTE (p-value 0.189), the MP-PPL clot-based assay showed measurable difference between the two groups, both as an absolute value and as a ratio (p-value: 0.04 and 0.038 respectively, Table 1). Peak thrombin generation (p-value 0.001), estimated thrombin potential (ETP) - (p-value 0.02) and velocity index (p-value 0.001) were significantly higher in subjects with line-associated VTE (see Figure 1). Subject recruitment and sample analyses, involving these assays and other potential biomarker candidates, are ongoing.Conclusion: Given the rising incidence of pediatric VTE, the ability to use biomarkers to stratify patients according to their VTE risk will provide a vital tool to guide preventative efforts, and minimizing unnecessary expense and toxicities. TGA and MP-PPL have shown great potential for differentiating children with CVLs that may develop a line-related VTE as a HA-VTE. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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Introduction: Although venous thromboembolism (VTE) risk factors for pediatric trauma patients have been identified in recent literature, overall low occurrence rates have resulted in minimal guidance on risk assessments and prophylaxis regimens. Methods: A single center retrospective chart review of patients 17 years of age and younger admitted to the Pediatric Trauma Service between July 1, 2008 and December 1, 2011 was conducted. A VTE risk assessment was developed and retrospectively applied to each patient to determine appropriateness of VTE prophylaxis. Results: Eight hundred four patients met initial inclusion criteria. Of these, 200 were evaluated with the VTE risk assessment and included for review. The median age was 11 years (IQR 5–16). One hundred twenty-five patients (62%) received appropriate prophylaxis. Reasons for inappropriate prophylaxis were a lack of sequential compression device (SCD) orders in 55 patients (73%), lack of pharmacologic prophylaxis orders in 14 patients (19%), and pharmacologic prophylaxis orders when not indicated by the risk assessment in six patients (8%). Pharmacologic prophylaxis was prescribed in 28% of patients. VTE occurred in four patients. Risk factors for VTE were an elevated Injury Severity score (p=0.03), lower Glasgow Coma Scale score (p=0.03), and the presence of central venous lines (p=0.004). Median ICU length of stay for patients with and without a VTE was nine (IQR 7–45) vs two days (IQR 0–4), respectively (p=0.006). Median hospital length of stay was 25 (IQR 14–51) vs six days (IQR 4–11), respectively (p=0.008). One bleeding event occurred (0.5%) in a patient receiving treatment dose anticoagulation. There was one death unrelated to VTE events. Conclusions: Though VTE prophylaxis is commonly administered to pediatric patients at this trauma center, adherence (62%) has room for improvement according to the study VTE risk assessment and recommendations. A standard VTE risk assessment and protocol may be beneficial in this population to ensure consistent prophylaxis.

Management of Thrombotic Complications in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children, and has been reported as the most common malignancy associated with thromboembolism in the pediatric age group. Treatment with Escherichia coli asparaginase, concomitant steroids, presence of central venous lines, and thrombophilic abnormalities are established risk factors for thromboembolism. The incidence varies with age, co-morbidities and chemotherapy regimens but the risk is highest during the induction and intensification phases. Treatment is necessary in majority of children to prevent serious sequelae. Mortality from thromboembolic events in any location is 2 to 4 % and the risk of recurrence is 7 to 10 %, further enhanced in the setting of malignancy. Randomized trials of venous thromboembolism (VTE) management in pediatric patients with ALL are lacking due to the low overall incidence, resulting in considerable variation in practice. The objective of this article is to review current knowledge on the treatment and prevention of thrombosis associated with pediatric ALL.

Thrombosis and acute leukemia

Thrombosis is a common complication in patients with acute leukemia. While the presence of central venous lines, concomitant steroids, the use of Escherichia coli asparaginase and hereditary thrombophilic abnormalities are known risk factors for thrombosis in children, information on the pathogenesis, risk factors, and clinical outcome of thrombosis in adult patients with acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is still scarce. Expert consensus and guidelines regarding leukemia-specific risk factors, thrombosis prevention, and treatment strategies, as well as optimal type of central venous catheter in acute leukemia patients are required. It is likely that each subtype of acute leukemia represents a different setting for the development of thrombosis and the risk of bleeding. This is perhaps due to a combination of different disease-specific pathogenic mechanisms of thrombosis, including the type of chemotherapy protocol chosen, the underlying patients health, associated risk factors, as well as the biology of the disease itself. The risk of thrombosis may also vary according to ethnicity and prevalence of hereditary risk factors for thrombosis; thus, it is advisable for Latin American, Asian, and African countries to report on their specific patient population.

Racial Differences In Pediatric Venous Thromboembolism

AbstractAbstract 3176 Background:Racial differences in the prevalence, risk factors, outcomes and recurrence rates of venous thromboembolism (VTE) have been reported in adults with the highest prevalence in African American (AA) males. Individuals of AA origin also have higher incidence of pulmonary embolism and increased mortality as compared to Caucasians. Such data are unknown in childhood VTE. Aim:Our aim was to evaluate the racial differences in risk factors, treatment response, outcomes and risks for recurrence in childhood VTE at a single center. Materials and Methods:All patients presenting to the pediatric hematology oncology service at this large urban Children's Hospital were followed prospectively from 2000–2010 and analyzed in a systematic manner. Data were analyzed using the SPSS v.17 software after approval from the institutional review board. Results:Preliminary analysis revealed that two hundred and eighteen patients with VTE were followed. There were 105 (48.2%) AA, 100 (45.9%) Caucasian (C), 4 (1.8 %) Middle Eastern (ME), 4(1.8%) Hispanic (H) and 5 Asian/Pacific islander (API) patients. Differences between AA and C were analyzed.Of the AA patients, there were 52 females (F), 53 males (M); Sites of presentation were upper extremity (UE) 12, lower extremity (LE) 24, pulmonary embolism (PE) 25, cortical sinus thrombosis (CST) 5, jugular (J) 13, vena caval (VC) 10, hepatic (H) 2 and cardiac atrial (CA) 8. Thirty six patients had more than one site at presentation. Of the Caucasian patients, there 51 F and 49 M; Sites of presentation were UE 12, LE 25, PE 17, CST 16, H 3, CA 8, VC 9, jugular 7, renal 3. Twenty four patients had more than one site of presentation.In AA patients, risk factors were persistently elevated D-Dimer and FVIII levels in 34 (32.4%) and 14 (13.3%) patients respectively; Elevated Lipoprotein (a){Lp(a)} in 24 (22.9%), positive cardiolipin antibodies (ACLA) in 11 (10.5%), ANA 18 (17.1%), and Lupus anticoagulant in 15 (14.3%) of patients. There were no patients with the Factor V Leiden (FVL) or the Prothrombin gene mutation. Clinical risk factors included the presence of central venous lines (CVL) in 58.1%, obesity in 26.7% and major surgery and immobilization in 36.2% and 30.5% respectively. Thirty percent of AA patients had positive family history of thrombosis in immediate family members.In Caucasian patients, risk factors were persistently elevated D- Dimer and FVIII levels in 19 (19%) and 13 (13%); antithrombin III deficiency in 3 (3%), heterozygous FVL in 10 (10%) and the Prothrombin gene variant in 3 (3%); Positive ACLA in 8(8 %), ANA in 11 (11%) and LA in 4 (4%), Elevated Lp(a) in 11 (11%). Clinical risk factors included presence of central venous lines (CVL) in 44.1%, obesity in 22% and major surgery and immobilization in 31% each. Interestingly, 30% of Caucasian patients had a positive family history of thrombosis in immediate family membersIn AA patients, 61.4% had complete (CR) or partial resolution (PR); in C patients 68.4% had CR or PR. Eleven (10%) AA and 7 (7%) C patients had recurrent events.There were no statistically significant differences in gender, laboratory and clinical risk factors and outcomes between African American and Caucasian patients analyzed. As anticipated, the FVL and Prothrombin gene variants were not seen in AA patients. Conclusions:In contrast to adults, there were no racial differences in presentation, risk factors and outcomes between Caucasian and African American patients with VTE followed at this single Children's Hospital thrombosis center. We believe this is the first report on racial differences in pediatric VTE. Larger population based studies are needed to confirm these findings. Disclosures:No relevant conflicts of interest to declare.

Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study

AbstractAmong risk factors for developing thromboembolism (VTE) in children with acute lymphoblastic leukemia were Escherichia coli asparaginase, concomitant steroid use, presence of central venous lines, and thrombophilic abnormalities. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to high-risk groups (HRGs). Predictive variables were incorporated into a risk assessment model, which was evaluated in 456 children and then validated in 339 patients. VTE risk by score was no greater than 2.5 for low-risk group (LRG) and greater than 2.5 for HRG. VTE rates at 3.5 months (validation cohorts) were 2.5% in LRG and 64.7% in HRG. In multivariate analysis adjusted for age, duration of asparaginase administration, enoxaparin prophylaxis, and T-immunophenotype, the HRG was significantly associated with VTE compared with the LRG (hazard/95% confidence interval [CI], 8.22/1.85-36.53). Model specificity was 96.2% and sensitivity was 63.2%. As secondary objective we investigated the use of enoxaparin for VTE prophylaxis in the HRG. HRG patients without enoxaparin prophylaxis showed a significantly reduced thrombosis-free survival compared with children on low-molecular-weight heparin (LMWH). On the basis of the high specificity, the model may identify children with leukemia at risk of VTE. LMWH may help prevent VTE in the HRG; this warrants assessment in larger cooperative clinical trials.

Microbial Etiology of Febrile Neutropenia

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case-control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E.coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns.

Validation of a Predictive Model for Indentifying An Increased Risk for Thromboembolism in Children with Acute Lymphoblastic Leukemia: Results of a Multicenter Cohort Study

Children with acute lymphoblastic leukemia (ALL) are at increased risk for venous thromboembolism (VTE), however, not all children experience a VTE. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to only high risk groups. A recent meta-analysis of studies in VTE in children with ALL identified four potential risk factors:treatment with Escherichia coli asparaginase (CASP),concomitant use of steroids,presence of central venous lines andthrombophilic genetic abnormalities.As VTE in childhood ALL is well recognized as serious clinical problem and due to the lack of studies on prevention, the standard of practice varies and some centres use enoxaparin prophylaxis for these children. However, the risks and benefits of the intervention are unknown. The aim of the study wasto develop a simple model for predicting ALL-chemotherapy-associated VTE using baseline clinical and laboratory variables, andto evaluate, on an explorative basis, the increasing off-label use of enoxaparin for VTE prophylaxis in ALL children.For development of the risk model the predictive variables were scored as follows: treatment with CASP (5000–10000/m2) in combination with prednisone or dexamethasone, presence of central venous lines, thrombophilic genetic abnormalities, e.g. positive family history for VTE or identification of a single thrombophilic trait (1 point each), or carrier status of combined thrombophilic traits (2 points). A definition of VTE risk by score was low (1–2) and high (□ 3). The risk score was than prospectively validated in an independent cohort of 136 newly recruited patients enrolled into the German database. Seven patients were excluded (lost to follow-up n=2; death n=2, secondary malignancy, VTE before ALL-onset, infant < 12 months of age: each n=1). The cumulative VTE rates at 3.5 months in the validation cohorts were 3.6% (95% CI 1%–9%) in the low-risk group (4 of 112), and 47% (95%CI 23%–72%) in the high-risk category (8 of 17). In multivariate analysis [Cox regression] the high risk group was significantly associated with VTE when compared to the low risk group even after adjusting for age at ALL-onset, duration of CASP administration, steroid administered (prednisone/dexamethasone), and presence or absence of enoxaparin prophylaxis [hazard/95%CI: 4.16/1.13–15.34]. The negative predictive value for VTE was 96.3% [95%CI: 92.9–99.8]. Early enoxaparin prophylaxis reduced the absolute VTE-risk about 60% [95%CI: 23–96]. Therefore, the model can identify ALL-children with an increased risk for symptomatic VTE.