Citations

Background: Coagulopathy and thrombosis are well-described complications of asparaginase therapy. However, treatment practices in pediatric hematology/oncology (PHO) patients vary widely as evidence-based guidelines for clinical management of these complications in this population are lacking. Objective: The objective of this study was to assess management practices of asparaginase-related coagulopathy by pediatric hematologist/oncologist attending physicians. Design/Method: Email survey sent to 2327 PHO physicians primarily practicing in the United States. Results: Two hundred eighty-five (12.2%) attending physicians completed the survey. Only 4.6% (n=13/285) routinely prescribe prophylactic anticoagulation during induction chemotherapy for leukemia. Slightly more than half (n=145/250, 50.9%) of all providers perform baseline coagulation studies. Most providers that were surveyed (n=185/285, 64.9%) only replete coagulant factors if the patient experiences bleeding or bruising. One hundred thirty (n=130/285, 45.6%) physicians replace low fibrinogen. The median fibrinogen replacement was 100 mg/dL (range: 40 to 200 mg/dL) with the median target of at least 100 mg/dL (range: 50 to 200 mg/dL). A minority of physicians (n=39/250, 13.7%) replace low antithrombin. The median antithrombin cutoff activity level was 60% (range: 40% to 100%) with a median target of 75% (range: 40% to 125%). Conclusions: There is a significant variation in PHO physician practices for monitoring and management of asparaginase-associated hemostatic derangements. Evidence-based guidelines have the potential to standardize practices.

BACKGROUND: Coagulopathy and thrombosis are well-described complications of asparaginase therapy; however, treatment practices in pediatric hematology oncology patients vary widely as evidence-based guidelines for clinical management of these complications in this population are lacking. OBJECTIVE: To assess management practices of asparaginase-related coagulopathy by pediatric hematology oncology (PHO) providers. DESIGN/METHOD: Email survey sent to 2,327 PHO providers primarily practicing in the United States. RESULTS: Two hundred and eighty-five (12.2%) attending physicians completed the survey. Only 4.6% (n=13/285) routinely prescribe prophylactic anticoagulation during induction chemotherapy for leukemia. Slightly more than half (n=145/250, 50.9%) of all providers perform baseline coagulation studies. Most providers that were surveyed (n= 185/285, 64.9%) only replete coagulant factors if the patient experiences bleeding or bruising. One hundred and thirty (n = 130/285, 45.6%) physicians replace low fibrinogen, and the median replacement was 100 mg/dL (range: 40-200 mg/dL) with the median target of at least 100 mg/dL (range: 50-200 mg/dL). A minority of physicians (n=39/250, 13.7%) replace low antithrombin at a median cutoff activity level of 60% (range 40-100 %) with a median target of 75% (range: 40-125 %). CONCLUSION: There is a significant variation in PHO provider practices for monitoring and management of asparaginase-associated hemostatic derangements. Evidence-based guidelines have the potential to standardize practices.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant hereditary disorder that results in arteriovenous malformations (AVMs) in the nose, mucocutaneous surfaces and visceral organs, including lung, brain, liver, bowel and rarely spinal cord. We describe a case of a young child with HHT who presented with acute paraparesis due to acute thrombosis of a spinal perimedullary arteriovenous fistula. Patient underwent coil embolization of spinal arteriovenous shunt with resolution of clinical symptoms. This case highlights the possibility of catastrophic complications in young children with HHT, the potential preventive role of screening for spinal AVMs in HHT and the importance of timely intervention.

Venous thromboembolism (VTE) is a life-threatening complication rarely encountered with the use of combined oral contraceptives (COCs). Obesity is an additional thrombosis risk factor that has been shown to further increase the risk of VTE with the use of COCs. We present 5 cases of obese adolescents (body mass index >30 kg/m2) who encountered thrombosis complications while on COCs. Although the absolute risk of VTE events in the setting of COCs is rare, caution should be observed when choosing hormonal therapy and safer COCs alternatives discussed with adolescents who are obese.

Myxopapillary ependymomas (MPEs) have an indolent clinical course, corresponding to World Health Organization Grade I. A total of 13 pediatric MPEs have been reported in the literature with “anaplastic features,” including elevated proliferative activity (≥5 mitoses/10 high-power fields), necrosis, and microvascular proliferation. No consensus exists regarding the prognostic significance of such features. A retrospective clinicopathologic review of pediatric MPEs diagnosed between 1996 and 2018 at Mayo Clinic was performed. Totally, 8 pediatric MPEs (6 male; age: 7.52 to 16.88 y) were identified. Totally, 3 had disseminated disease at presentation. All patients underwent surgical resection (7 gross total; 1 subtotal). Totally, 5 cases harbored ≥5 mitoses/10 high-power fields (range: 5 to 9), 3 of which showed necrosis (2 with disseminated disease). Postsurgery, 2 patients received radiation; one with disseminated disease and another with increased mitotic activity/necrosis; neither has recurred (follow-up: 1.18 and 3.19 y). In all, 2 patients with disseminated disease, elevated mitotic activity, and necrosis had new metastatic disease/progression of nonresected metastatic foci (2.6 and 26.8 mo), received radiation therapy, and remain progression free (3.01 and 9.34 y). All patients are alive (median follow-up 1.31 y, range: 0.66 to 11.75). Among pediatric MPEs, the concurrent presence of elevated mitotic activity and necrosis may be associated with an aggressive clinical course, warranting closer surveillance and consideration of adjuvant therapies.

AbstractBackgroundThe electronic health record (EHR) is a contributor to serious patient harm occurring within a sociotechnical system. Chemotherapy ordering is a high‐risk task due to the complex nature of ordering workflows and potential detrimental effects if wrong chemotherapeutic doses are administered. Many chemotherapy ordering errors cannot be mitigated through systems‐based changes due to the limited extent to which individual institutions are able to customize proprietary EHR software. We hypothesized that simulation‐based training could improve providers’ ability to identify and mitigate common chemotherapy ordering errors.MethodsPediatric hematology/oncology providers voluntarily participated in simulations using an EHR testing (“Playground”) environment. The number of safety risks identified and mitigated by each provider at baseline was recorded. Risks were reviewed one‐on‐one after initial simulations and at a group “lunch‐and‐learn” session. At three‐month follow‐up, repeat simulations assessed for improvements in error identification and mitigation, and providers were surveyed about prevention of real‐life safety events.ResultsThe 8 participating providers identified and mitigated an average of 5.5 out of 10 safety risks during the initial simulation, compared 7.4 safety risks at the follow up simulation (p=0.030). Two of the providers (25%) reported preventing at least one real‐world patient safety event in the clinical setting as a result of the initial training session.ConclusionsSimulation‐based training may reduce providers’ susceptibility to chemotherapy ordering safety vulnerabilities within the EHR. This approach may be used when systems‐based EHR improvements are not feasible due to limited ability to customize local instances of proprietary EHR software.

Abstract Heparin-induced thrombocytopenia (HIT) is a life-threatening, prothrombotic, antibody-mediated disorder. To maximize the likelihood of recovery, early and accurate diagnosis is critical. Widely available HIT assays, such as the platelet factor 4 (PF4) heparin enzyme-linked immunosorbent assay (ELISA) lack specificity, and the gold-standard carbon 14–labeled serotonin release assay (SRA) is of limited value for early patient management because it is available only through reference laboratories. Recent studies have demonstrated that pathogenic HIT antibodies selectively activate PF4-treated platelets and that a technically simpler assay, the PF4-dependent P-selectin expression assay (PEA), may provide an option for rapid and conclusive results. Based upon predefined criteria that combined 4Ts scores and HIT ELISA results, 409 consecutive adults suspected of having HIT were classified as disease positive, negative, or indeterminate. Patients deemed HIT indeterminate were considered disease negative in the primary analysis and disease positive in a sensitivity analysis. The ability of PEA and SRA to identify patients judged to have HIT was compared using receiver operating characteristic curve statistics. Using these predefined criteria, the diagnostic accuracy of PEA was high (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.87-1.0) and similar to that of SRA (AUC, 0.91; 95% CI, 0.82-1.0). In sensitivity analysis, the AUCs of PEA and SRA were also similar at 0.88 (95% CI, 0.78-0.98) and 0.86 (95% CI, 0.77-0.96), respectively. The PEA, a technically simple nonradioactive assay that uses ∼20-fold fewer platelets compared with the SRA, had high accuracy for diagnosing HIT. Widespread use of the PEA may facilitate timely and more effective management of patients with suspected HIT.

Abstract Introduction May–Thurner syndrome (MTS) is a vascular anatomic variant resulting in compression of the left common iliac vein by the right common iliac artery, affecting approximately 22% of the population. In adults, following acute deep vein thrombosis (DVT) of the iliofemoral veins, the incidence of postthrombotic syndrome (PTS) and recurrent DVT are high if treated with anticoagulation alone, warranting adjunctive treatment with thrombolysis and stent placement. However, there is paucity of literature documenting the course of treatment and associated outcomes in pediatric patients with MTS. Methods A retrospective chart review of pediatric patients (≤ 18 years of age) with radiologic confirmation of MTS with or without DVT evaluated and/or treated at our institution from January 1, 2005 through December 31, 2015 was conducted. Results Seventeen patients (4 male; 13 female) were identified. Median age was 15.4 years (range 8.8–17.1 years) with a median follow-up of 1.2 years (range 0.4–7.5 years). Thirteen (76.5%) patients presented with left lower extremity DVT. Management included catheter-directed thrombolysis (n = 5), systemic thrombolysis (n = 1), and mechanical thrombectomy (n = 1). Fifteen patients were treated with anticoagulation including two patients with endovascular stents without DVT. Median duration of anticoagulation was 6.3 months (range 3.2–18.7 months). Ten patients (59%) underwent stent placements.Complete and partial thrombus resolution was noted in six patients each and no resolution in one patient. Four patients had recurrence/progression of thrombus (n = 3 with stents) at a median time of 29 days (range 12–495 days). No bleeding complications were observed. Clinically documented or self-reported PTS was noted in 8 patients (62%). Conclusion There are no clear guidelines for MTS management in children and adolescents. In our cohort, thrombolysis, anticoagulation, or stent placements were not associated with bleeding risks, with recurrence/progression of DVT and signs and symptoms of PTS noted in 30 and 62%, respectively. Further studies are needed to determine a standardized treatment approach of the pediatric patient with MTS with or without thrombosis.

Venous thromboembolism (VTE) is a life-threatening complication rarely encountered with the use of combined oral contraceptives (COCs). Obesity is an additional thrombosis risk factor that has been shown to further increase the risk of VTE with the use of COCs. We present five cases of obese adolescents (BMI >30 kg/m2) who encountered thrombosis complications while on COCs. Although the absolute risk of VTE events in the setting of COCs is rare, caution should be observed when choosing hormonal therapy and safer COCs alternatives discussed with adolescents who are obese.