American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism

Abstract

Background: Despite an increasing incidence of venous thromboembolism (VTE) in pediatric patients in tertiary care settings, relatively few pediatric physicians have experience with antithrombotic interventions. Objective: These guidelines of the American Society of Hematology (ASH), based on the best available evidence, are intended to support patients, clinicians, and other health care professionals in their decisions about management of pediatric VTE. Methods: ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews (up to April of 2017). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 30 recommendations, covering symptomatic and asymptomatic deep vein thrombosis, with specific focus on management of central venous access device–associated VTE. The panel also addressed renal and portal vein thrombosis, cerebral sino venous thrombosis, and homozygous protein C deficiency. Conclusions: Although the panel offered many recommendations, additional research is required. Priorities include understanding the natural history of asymptomatic thrombosis, determining subgroup boundaries that enable risk stratification of children for escalation of treatment, and appropriate study of newer anticoagulant agents in children.

Capped antithrombin III dosing is cost effective in the management of asparaginase‐associated thrombosis

“…Due to acquired ATIII deficiency following asparaginase administration, the institutional practice at Cincinnati Children's Hospital Medical Center (CCHMC) for patients treated with enoxaparin is to monitor and replace ATIII during asparaginase therapy. Achieving therapeutic anticoagulation with enoxaparin is dependent on adequate ATIII levels . Labeled dosing for ATIII repletion is calculated based upon actual ATIII activity level, goal level, and patient weight [ATIII dose = ((goal ATIII% − serum ATIII%) × weight in kg) / 1.4].…”

“…Achieving therapeutic anticoagulation with enoxaparin is dependent on adequate ATIII levels. 6 institutionally defined threshold for ATIII repletion is less than 70%, with dosing calculated to a goal of 120%. Driven by a cost-savings initiative, capped ATIII dosing with concurrent post-infusion peak monitoring was implemented.…”

Differential effects of direct factor IIa and factor Xa inhibitors in protein C‐deficient plasma detected using thrombin generation and viscoelastometry assays

“…Oral vitamin K antagonists (VKA) may be useful adjuncts to PC replacement to prevent acute exacerbations of coagulopathy, or when treatment with PC concentrate is unfeasible . However, VKA increase bleeding risk compared with PC replacement alone, particularly when there is an active consumptive coagulopathy . VKA may also paradoxically increase thrombosis risk in patients with low‐level residual PC synthesis because of inhibition of vitamin K‐dependent PC post‐translational modifications …”

“…[8][9][10] Current standard long-term care of severe PC deficiency comprises PC replacement therapy with plasma-derived PC concentrate to correct coagulopathy and prevent thrombosis. 11 Oral vitamin K antagonists (VKA) may be useful adjuncts to PC replacement to prevent acute exacerbations of coagulopathy, or when treatment with PC concentrate is unfeasible. 7,8,12 However, VKA increase bleeding risk compared with PC replacement alone, particularly when there is an active consumptive coagulopathy.…”

“…7,8,12 However, VKA increase bleeding risk compared with PC replacement alone, particularly when there is an active consumptive coagulopathy. 11 VKA may also paradoxically increase thrombosis risk in patients with low-level residual PC synthesis because of inhibition of vitamin K-dependent PC post-translational modifications. 13 The low-molecular-weight heparins (LMWH) that inhibit both FXa and FIIa indirectly through antithrombin, and the direct-acting oral anticoagulants (DOACs) that are selective FIIa and FXa inhibitors have been evaluated widely in adults for the prevention and treatment of VTE.…”