Direct oral anticoagulants toxicity in children: an overview and practical guide

By increasing use of direct oral anticoagulants (DOACs) in adults and children, gradual increase in the number of intentional or unintentional DOAC poisonings among children is suspected in the near future. Hence, clinicians and pharmacists need to be familiar with the clinical features and management of DOAC-toxicity among pediatric population. This article provides an overview and practical guide to DOAC-toxicity in pediatrics according to the available clinical evidence. Based on limited available data, accidental pediatric ingestion of DOACs can be managed by supportive care in most cases. However, serious toxicity may occur following massive overdose, in presence of underlying disorders (renal or hepatic dysfunction) and concurrent anticoagulant therapy. Activated charcoal is recommended for known recent ingestion of DOACs (within 2–4 hours) to reduce the gastrointestinal absorption. Supportive interventions including local hemostatic measures and volume resuscitation are the cornerstone of management of bleeding. Vitamin K and fresh frozen plasma are ineffective for DOAC reversal and thus are not recommended. Currently, safety and efficacy data regarding the use of specific reversal agents (including idarucizumab and andexanet alfa) and 3-factor or 4-factor prothrombin complex concentrate (PCC) or activated PCC (aPCC) among children with DOAC-associated bleeding are lacking.随着成人与儿童人群直接口服抗凝药（direct oral anticoagulants, DOACs）使用量的持续增加，预计近期儿童因故意或意外服用DOAC导致的中毒病例数将逐步上升。因此，临床医师与药师需熟悉儿科人群DOAC中毒的临床特征与处置方案。本文基于现有临床证据，对儿科DOAC中毒的诊疗进行综述并提供实用指导。基于现有有限数据，大多数儿童意外服用DOAC的病例可通过支持治疗进行处置。但在大规模过量服药、合并基础疾病（肾功能或肝功能不全）以及同时接受抗凝治疗的情况下，可能会出现严重中毒反应。若患儿在2~4小时内明确服用过DOAC，推荐使用活性炭以减少胃肠道吸收。包括局部止血措施与容量复苏在内的支持性干预，是出血处置的核心手段。维生素K与新鲜冰冻血浆无法逆转DOAC的抗凝作用，因此不推荐使用。目前，针对DOAC相关出血的儿童患者，使用特定逆转剂（包括依达赛珠单抗（idarucizumab）与安德沙奈α（andexanet alfa））以及3因子或4因子凝血酶原复合物浓缩物（PCC）、活化PCC（aPCC）的安全性与有效性数据仍较为缺乏。