Thromboprophylaxis in pregnant women: For whom and which LMWH dosage? Reply
Thromboprophylaxis in pregnant women: For whom and which LMWH dosage? Reply
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孕妇的血栓预防：针对谁以及哪种 LMWH 剂量？
DOI：
10.1111/jth.14546
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发表时间：
2019
影响因子：
10.4
通讯作者：
R. Eslick
中科院分区：
文献类型：
--
作者：
C. McLintock;S. Cox;R. Eslick
我们感到非常鼓舞的是，我们的研究引起了这样一个深思熟虑和深思熟虑的反应;值得祝贺的是，其作者正在进行第一次随机临床研究，探索最佳低分子量肝素（LMWH）剂量，以预防被认为有高危静脉血栓栓塞（VTE）个人病史的女性发生妊娠相关静脉血栓栓塞（VTE）。有VTE个人病史的女性被排除在LMWH给药研究之外，我们同意在这种临床环境中存在与不同剂量LMWH有效性相关的知识缺口。然而，可以说有一个更基本的知识差距，应该首先解决。来自妊娠相关静脉血栓栓塞研究的数据表明，约十分之一有静脉血栓栓塞病史的女性在妊娠期间和产后有复发性静脉血栓栓塞的风险，但尽管如此，迄今为止，尚未发表大型随机临床研究，以确定血栓预防与单独临床观察相比的安全性和有效性。妊娠相关性VTE的风险在既往发生过与激素风险因素相关的VTE的女性中最高（即，联合口服避孕药或怀孕或有无端事件）。临床医生继续遵循基于低水平证据的解释2，尽管经过仔细考虑，这导致在怀孕期间和产后被认为处于最高风险的大量女性接受血栓预防。尽管LMWH不会穿过胎盘，因此对胎儿的不良影响没有安全性问题，但显然使用任何抗凝剂都可能增加出血并发症的风险。由于缺乏临床试验数据来解决这一关键的知识差距，使得在该领域执业的临床医生面临着血栓预防被过度使用的批评。3我们与作者一样，对在妊娠环境中进行临床试验的困难感到沮丧，以及导致HighLow研究1中的研究者决定使用不同的LMWH制剂的务实原因。然而，正如我们在论文中所指出的，即使是“低剂量”LMWH方案也是经过体重调整的，我们只是担心这样的剂量范围会引入一定程度的复杂性，这可能会使研究结果难以解释并将结果转化为临床实践。
We are very encouraged that our study has provoked such a thoughtful and considered response; its authors are to be congratulated that they are carrying out the first randomized clinical exploring optimal low‐ molecular‐weight heparin (LMWH) dosing for prevention of preg‐ nancy‐associated venous thromboembolism (VTE) in women consid‐ ered to have a personal history of high‐risk VTE.1 As they state, women with personal history of VTE been excluded from studies of LMWH dosing, and we agree that there is a knowledge gap relating to the ef‐ ficacy of different doses of LMWH in this clinical setting. However, arguably there is a more fundamental knowledge gap that should be addressed first. Data compiled from studies of pregnancy‐associated venous thromboembolism suggest that around one in 10 women with a personal history of VTE are at risk of recurrent VTE during pregnancy and in the postpartum,2 but despite this, to date, there is no large ran‐ domized clinical study published that establishes the safety and effi‐ cacy of thromboprophylaxis compared with clinical observation alone. The risk of pregnancy‐associated VTE is highest in women who have had previous VTE associated with hormonal risk factors (i.e., the com‐ bined oral contraceptive pill or pregnancy or who have had unprovoked events). Clinicians continue to follow recommendations2 that are based on low‐level evidence, albeit carefully considered, which leads to pre‐ scription of thromboprophylaxis to large numbers of women during pregnancy and in the postpartum who are perceived to be at highest risk. Although there is no safety concern regarding an adverse fetal effect of LMWH because the drug does not cross the placenta, clearly the use of any anticoagulant could introduce an increased risk of bleed‐ ing complications. The lack of data from a clinical trial that addresses this critical knowledge gap leaves clinicians practicing in the field open to the criticism that thromboprophylaxis is overused.3 We share the authors’ frustrations at the difficulty at carrying out clinical trials in the setting of pregnancy and the pragmatic reasons that led to the decision investigators in the HighLow study1 should be able to use different preparations of LMWH. However, as we out‐ lined in our paper, even the “low‐dose” LMWH regimens are weight‐ adjusted, and we are simply concerned that such a range of doses introduces a degree of complexity that may make it difficult to inter‐ pret the study outcomes and translate findings into clinical practice.