摘要：2024年12月7~10日，第66届美国血液学会（ASH）年会在美国圣迭戈隆重召开，全球血液学专家学者齐聚一堂，共同对血液领域最新研究进展进行深入探讨与交流。在本届大会上，墨尔本大学皇家儿童医院Paul Monagle教授主持开展了“ASH ISTH Clin

编者按：2024年12月7~10日，第66届美国血液学会（ASH）年会在美国圣迭戈隆重召开，全球血液学专家学者齐聚一堂，共同对血液领域最新研究进展进行深入探讨与交流。在本届大会上，墨尔本大学皇家儿童医院Paul Monagle教授主持开展了“ASH ISTH Clinical Practice Guidelines on Treatment of Venous Thromboembolism (VTE) in Pediatric Patients（儿童深静脉血栓治疗的ASH ISTH临床实践指南）”的专题会议，探讨了儿童VTE的发病情况、治疗指南更新及治疗建议等内容。为了深入了解该方面的内容，《肿瘤瞭望-血液时讯》围绕儿童VTE的相关内容特邀采访了Paul Monagle教授，现整理如下。

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《肿瘤瞭望-血液时讯》：儿童深静脉血栓（VTE）的发病率相对较低，但呈上升趋势，首先请您介绍一下儿童VTE的流行病学和发病机制？

Paul Monagle教授：儿童静脉血栓（VTE）与成人静脉血栓存在很大的差异，绝大部分的儿童VTE发生于住院患儿当中，其主要的诱因当然首推中心静脉导管的置入。此外，患有恶性肿瘤或接受过重大手术的住院患儿同样也好发静脉血栓（VTE）。这些因素带来了两大改变：它改变了患儿的抗凝能力和血栓的治疗结局，这是极其重要的区别，需要理解透彻。另外一个重要的区别在于，在VTE治疗方面，成人的VTE治疗重点为修复受损部分，尽量使其恢复至患病之前。但对于儿童而言，我们要确保其在未来的成年生活中的最大潜能不受影响。因此，这是一个完全不同的治疗模式。

Oncology Frontier-Hematology Frontier：The incidence of deep vein thrombosis (VTE) in children is relatively low, but it is on the rise. First, please introduce the epidemiology and pathogenesis of VTE in children?

Pro. Paul Monagle：Venous thrombosis in children is very different to venous thrombosis in adults because most of the venous thrombosis we see in children happen in sick hospitalized children. So, the major precipitating factor, of course, is central venous lines, but other children who are sick in hospital with cancer, having major surgery. So that changes two things, it changes the ability to anticoagulate of the children, and it also changes the outcomes for the thrombosis. And so that's a really important difference to understand. The other really important difference to understand when we're treating children compared to adults is that when we're treating adults, we're just trying to fix what was broken. We're trying to make them like they were before they got sick. But for children, we're trying to ensure that their unlimited potential is there for the rest of their adult life. So it's a totally different paradigm of treatment as well.

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《肿瘤瞭望-血液时讯》：最近，儿童的VTE指南进行了修订，能否请您解读一下其中更新的内容？

Paul Monagle教授：美国血液学会（ASH）的VTE治疗指南首次制定于2018年，从2018年至今，儿童VTE相关的临床试验数据显著增加，这主要得益于医药企业发起的（industry-sponsored）关于直接口服抗凝药（DOAC）的临床试验，围绕利伐沙班、达比加群以及当前的阿哌沙班等抗凝药进行了大型的临床研究，为我们提供了更多参与临床试验的VTE患儿数据。较之于2018年制定的原始指南，这些数据增加了10倍或更多，这就是指南需要更新的原因所在。一是因为我们有了更多的研究数据，二是因为儿童VTE的可用药物发生了显著变化。我们需要考虑到指南与当前临床实践的相关性问题。

Oncology Frontier-Hematology Frontier：Recently, the VTE guidelines for children have been modified, Could you please explain the updated part?

Pro. Paul Monagle： The ASH VTE treatment guidelines were first done in 2018. And since 2018 to now, there's been an explosion in the amount of trial data that is available in children. And that's predominantly because of the industry-sponsored DOAC trials that have taken place. Large trials of rivaroxaban, of dabigatran, and now of apixaban mean that we've now got more data on children who have been enrolled in clinical trials. By a factor of 10 or more compared to what we had to inform the original guidelines that were written in 2018.So that was why they needed to be updated. A because we had so much more data and B because the range of drugs that we could use in the children was different. So to keep the guidelines relevant to current practice, we need to be able to consider those things.

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《肿瘤瞭望-血液时讯》：能否谈一谈诱发性和非诱发性儿童VTE抗凝治疗的适应症和持续时间？

Paul Monagle教授：首先，应区分有症状性深静脉血栓（DVT）和无症状性DVT。对于有症状的DVT，我们通常认为需要治疗；而对于无症状性的DVT，是否需要治疗则不太明确。对于诱发性DVT而言，根据最近完成的KIDS临床试验，我们认为在抗凝治疗6周后，DVT已经消退或变为非阻塞性，因此在6周后停止治疗是安全的，其在儿童VTE中的疗效与继续治疗相同。然而，KIDS临床研究特意剔除了某些儿童人群，故其仅适用于无其它危险因素的儿童，即无潜在癌症、无易栓症或抗磷脂抗体。所有其它的诱发性DVT儿童，其治疗应达到3个月。对于非诱发性VTE儿童，我们认为应至少治疗6~12个月，显然，若为成人非诱导性VTE则需无限期治疗，但对于儿童而言，无限期抗凝治疗存在很大的问题，这对他们的生活质量和心理健康产生了巨大影响。因此，我们建议非诱发性VTE儿童至少治疗6~12个月，然后与家庭讨论治疗的优先级别，并根据家庭的价值观和偏好做出进一步决定。

Oncology Frontier-Hematology Frontier：Could you please talk about the indications and duration of anticoagulant therapy for VTE in provoked and unprovoked children?

Pro. Paul Monagle：The first distinction to make is the difference between symptomatic DVT and clinically unsuspected DVT. So, we're very comfortable that symptomatic DVT usually require treatment, whereas it's a lot less clear whether clinically unsuspected DVT in children require treatment. Then , if we have provoked DVT, what we now know predominantly from the Kids.Trial, which was completed recently, is that if you have a provoked DVT and at six weeks of treatment, that DVT is now resolved or has now become non-occlusive, that it is safe to stop treatment at six weeks and the children will do just as well as if you continued.

However, the Kids.Trial specifically excluded a population of children, so it's only in the specific children who do not have other risk factors.Who do not have an underlying cancer, do not have a thrombophilia or antiphospholipid antibody, that is appropriate. All other provoked VTE in children should be treated for three months.For unprovoked VTE in children, we think they should be treated for at least six to 12 months.Clearly in the adult phase, unprovoked VTE is treated indefinitely, but indefinite anticoagulation is very problematic for children.It has a huge impact on their quality of life and it has a huge impact on their mental health.So our recommendation is that children with unprovoked VTE should be treated for at least six to twelve months and then there should be a discussion with the family about the priorities of treatment and then further decisions made according to the family's values and preferences.

来源：肿瘤瞭望