The Israel National Hemophilia Centre, Thrombosis Unit, Sheba Medical Centre, The Sackler Medical School, Tel Aviv University, Tel-Hashomer Israel.
Best Pract Res Clin Haematol. 2012 Sep;25(3):333-44. doi: 10.1016/j.beha.2012.07.001. Epub 2012 Aug 15.
Thrombosis in children is gaining increased awareness, as advanced medical care has increased treatment intensity of hospitalized pediatric patients. Guidelines for diagnosis and treatment of children and neonates with venous thromboembolism (VTE) are mostly extrapolated from adult data, despite the uniqueness of their hemostatic system. Whereas inherited thrombophilia (IT) have been established as risk factors for VTE in adults, in children with idiopathic VTE and in pediatric populations in which thromboses were associated with medical diseases, IT have been described as additional risk factors. Follow-up data for VTE recurrence in children suggest a recurrence rate between 3% (neonates) and 21% (idiopathic VTE). Apart from underlying medical conditions, recently reported systematic reviews on pediatric VTE and stroke have shown significant associations between thrombosis and presence of factor V G1691A, factor II G20210A, protein C-, protein S- and antithrombin deficiency, even more pronounced when combined IT were involved. The pooled odds ratios (OR: single IT) for VTE onset ranged from 2.4 for the factor II G20210A mutation (cerebrovascular occlusion) to 9.4 in children with antithrombin deficiency (venous VTE). In addition, the pooled OR for persistent antiphospholipid antibodies/lupus anticoagulants was 6.6 for children with cerebrovascular occlusion and 4.9 for pediatric cases with venous VTE. The factor II G20210A mutation (OR: 2.1), protein C- (OR: 2.4), S- (OR: 3.1), and antithrombin deficiency (OR: 3.0) did also play a significant role at recurrence. Among primarily asymptomatic family members of pediatric VTE index cases annual VTE incidences were 2.82% (95% confidence interval [95% CI], 1.63-4.80%) in carriers of antithrombin, protein C, or protein S-deficiency, 0.42% (0.12-0.53%) for factor II G202010A, 0.25% (0.12-0.53%) for factor V G1691A, and 0.10% (0.06-0.17%) in relatives with no IT. Based on these data diagnosis, screening and treatment issues will be discussed.
儿童血栓形成越来越受到关注，因为先进的医疗护理增加了住院儿科患者的治疗强度。尽管儿童的止血系统具有独特性，但儿童和新生儿静脉血栓栓塞症（VTE）的诊断和治疗指南大多是从成人数据推断出来的。尽管遗传性血栓形成倾向（IT）已被确立为成人 VTE 的危险因素，但在特发性 VTE 患儿和与医疗疾病相关的儿科人群中，IT 已被描述为额外的危险因素。儿童 VTE 复发的随访数据表明，复发率在 3%（新生儿）至 21%（特发性 VTE）之间。除了基础疾病外，最近关于儿科 VTE 和中风的系统评价显示，血栓形成与因子 V G1691A、因子 II G20210A、蛋白 C-、蛋白 S-和抗凝血酶缺乏之间存在显著关联，当涉及到联合 IT 时，这种关联更为明显。VTE 发病的汇总优势比（OR：单一 IT）范围从因子 II G20210A 突变（脑血管闭塞）的 2.4 到抗凝血酶缺乏症患儿的 9.4（静脉 VTE）。此外，持续性抗磷脂抗体/狼疮抗凝物的汇总 OR 对于脑血管闭塞患儿为 6.6，对于儿科静脉 VTE 病例为 4.9。因子 II G20210A 突变（OR：2.1）、蛋白 C-（OR：2.4）、S-（OR：3.1）和抗凝血酶缺乏症（OR：3.0）在复发时也起着重要作用。在儿科 VTE 索引病例的主要无症状家族成员中，抗凝血酶、蛋白 C 或蛋白 S 缺乏症携带者的年度 VTE 发生率为 2.82%（95%置信区间[95%CI]，1.63-4.80%），因子 II G202010A 为 0.42%（0.12-0.53%），因子 V G1691A 为 0.25%（0.12-0.53%），无 IT 的亲属为 0.10%（0.06-0.17%）。基于这些数据，将讨论诊断、筛查和治疗问题。
