Rodriguez, Vilmarie

BACKGROUNDAlthough effective methods for venous thromboembolism prophylaxis (VTE‐P) have been known for decades, reliable implementation has been challenging.OBJECTIVEDevelop reliable VTE‐P systems for adult and for pediatric patients to reduce preventable venous thromboembolism (VTE).DESIGNWe used a discovery and diffusion system to first develop an effective system in 1 hospital location, and then spread the principle best practices across the entire 22‐hospital system.SETTINGTwenty‐two Mayo Clinic hospitals (adults and children).PATIENTSAdult and pediatric patients.INTERVENTION(1) Ensure that a VTE‐P is declared at admission by providing a mandatory VTE‐P “tollgate” that requires the provider to assess the risk for VTE and provide an appropriate order for VTE‐P. (2) Use clinical decision support to provide ongoing surveillance and alerts to providers when there is a lapse in the VTE‐P plan.MEASUREMENTSIn adults, VTE compliance as measured by the Centers for Medicare and Medicaid Services Core Measures VTE‐1 and VTE‐2, preventable VTE as measured by VTE‐6, and in pediatric patients, appropriate VTE measures as determined by chart audit.RESULTSVTE‐1 and VTE‐2 have approached 97% to 100% and preventable VTE has declined to 0% for the last 3 quarters. Similarly, the pediatric VTE‐P screening tool was evaluated and piloted with >92% compliance in risk documentation, appropriate VTE‐P >64%, and 0 VTE events during the study period.CONCLUSIONAn integrated system‐wide approach can lead to measurable improvements in VTE‐P process and outcome measures. Journal of Hospital Medicine 2016;11:S15–S21. © 2016 Society of Hospital Medicine

The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children’s Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance. Targeted toxicities included allergic reactions, anaphylaxis, pancreatitis, thrombosis, bleeding, central nervous system events, and sepsis. AALL08P1 enrolled 104 patients; 54 were classified as HR-Avg and 30 as HR-High after completion of induction therapy. Only 53% (16/30) of the HR-High patients received ≥8 total doses of I-PEG and 50% (15/30) took ≤49 weeks from start of Consolidation to the initiation of Maintenance. I-PEG did not significantly increase grade 2 to 5 targeted toxicities. I-PEG was not feasible or safe as defined in AALL08P1. Complete assessment of this regimen was limited due to removal of patients from I-PEG regimen and early closure of the study.

IntroductionCentral venous access devices (CVADs) are frequently required as stable long‐lasting venous access in children with haemophilia, especially those requiring immune tolerance induction (ITI) for inhibitors. CVAD infection is one of the most frequently reported catheter‐related complications in this patient population.AimDetailed review of CVAD complications from the International ITI (I‐ITI) study and analysis of potential risk factors for such complications.MethodsRetrospective analysis of prospectively obtained data from the I‐ITI study primarily focused on CVAD‐related complications.ResultsA total of 115 children were recruited and 183 CVADs were placed in 99 subjects resulting in 121,206 CVAD‐days observed on‐study. A total of 124 CVAD infections were reported in 41 of 99 (41%) subjects with an overall infection rate of 0.94 per 1000 CVAD‐days (interquartile ranges 0–1.7). A similar number of infections were observed in the two treatment arms (median: 2 and 3 in high dose and low dose respectively). Infections occurred more frequently in the presence of external catheters than with fully implanted catheters (P = 0.026). Infected patients were significantly younger at the time of CVAD insertion (median age: 22 vs. 25 months, P = 0.020). Patients with Gram‐positive infections were also significantly younger than those with Gram‐negative infections (median age: 17 vs. 25 months, P < 0.0001).ConclusionCVAD infection was the most common complication observed in children with severe haemophilia and inhibitors in the frame of the I‐ITI study. Younger age at CVAD insertion and external CVAD were associated with higher risk for infection. ITI outcome was unaffected by CVAD infections.

AbstractGuanine‐adenine‐thymine‐adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature. Varying clinical presentations offer diagnostic challenges. Allogeneic stem cell transplant remains the treatment of choice. Morbidity, mortality, and social costs due to the familial nature of the disease are considerable. We describe our experience with the disorder in three affected families and a comprehensive review of current literature.

SummaryHaemorrhagic complications remain a challenge with surgical procedures in patients with bleeding disorders. In children and young adults, the most commonly performed surgeries are tonsillectomies and/or adenoidectomies. Adequate haemostasis in these patients with bleeding disorders is centred on comprehensive perioperative haemostatic support and dexterous surgical technique. The aim of this study was to assess postoperative bleeding complications with tonsillectomy and/or adenoidectomy in children and young adults with known bleeding disorders. Retrospective review of all patients aged <25 years with known bleeding disorders who underwent tonsillectomy and/or adenoidectomy at Mayo Clinic, Rochester MN between July 1992 and July 2012. In contrast to reported literature, we observed a higher rate of bleeding complications (10/19, 53%) despite aggressive haemostatic support and appropriate surgical techniques. Delayed bleeding (>24 h postoperatively) was more common than early bleeding; and recurrent bleeding was associated with older age. Children and young adults with haemorrhagic diatheses undergoing adenotonsillectomy are at a higher risk of delayed bleeding and require close monitoring with haemostatic support for a prolonged duration in the postoperative period. A uniform approach is needed to manage these patients perioperatively by establishing standard practice guidelines and ultimately reduce postsurgical bleeding complications.

SummaryNeonatal circumcision in patients with severe haemophilia has not been well studied. We performed a survey of paediatric haematologists from Hemophilia Treatment Centers (HTC) across the United States to better understand the attitudes toward and management of neonatal circumcision in haemophilia patients. Response rate to our survey was 40% (n = 64/159). Thirty‐eight percent of respondents (n = 24) said that they would allow this procedure in the newborn period but in many cases this was against medical advice. The most reported concern regarding neonatal circumcision in haemophilia patients was the risk of development of an inhibitor (n = 25; 39%) followed by the concern for bleeding (n = 22; 34%) and issues related to vascular access in the neonate (n = 11; 17%). All respondents recommended at least one preprocedure dose of factor replacement. Twenty‐two percent (n = 14) of respondents did not use more than one dose of factor replacement but 32% (n = 21) used 1–2 postoperative doses. The remainder of paediatric haematologists surveyed recommended between 3–5 (16%; n = 10) and 6–10 (3%, n = 2) additional days postoperatively. There was wide variation in both techniques of circumcision as well as adjuvant haemostatic agents used. Only 22% of respondents said that they had an established protocol for management of circumcision in the newborn haemophilia patient. These survey results highlight the need for evidence‐based guidelines regarding the optimal management of circumcision in neonates with severe haemophilia.