International Circulation: Elderly patients with idiopathic pulmonary embolism (PE) are at high risk for recurrent venous thromboembolic disease. Might they benefit from long-term anticoagulant therapy？In addition， after long-term anticoagulant therapy， they also have higher risk for bleeding complications， how can we balance the competing needs of preventing bleeding complications while also providing needed anticoagulant therapy?

国际循环：老年特发性肺栓塞（PE）患者有很高的发生静脉血栓栓塞性疾病的风险。他们可能会受益于长期抗凝治疗吗？此外，长期进行抗凝治疗也有较高的出血并发症的风险，我们如何在提供必要的抗凝治疗和预防出血并发症间找到平衡？

Prof. Bauer: One must do an individualized assessment of the patient. Elderly people， like all patients， differ with respect to certain characteristics that may make them more likely to need thromboembolic protection from recurrent VTE. I have some individualized concerns that do not come from the guidelines. The guidelines largely are done based on randomized studies in relatively compliant patients who are easy to control with warfarin and with a very high bleeding risk. It depends on individual clinical characteristics of the patient including the nature of their clinical event and the severity of their clinical event. For example， if the event was pulmonary embolism， which is more serious than DVT， or if they have cardiopulmonary disease， which may give them less reserve if they were to suffer a recurrent event. These are some issues that may influence you to want to provide that protection. Therefore， there are certainly individual clinical risk factors in regard to thromboembolic risk.

Regarding the bleeding risk， what their profile is with respect to risk for bleeding. Obviously age is one factor but there are a number of clinical comorbidities that go with advanced age that place people at higher risk. People who have had prior bleeding events， people who have anemia， and those with chronic renal insufficiency have all been shown to be at higher risk. Perhaps most important is compliance and ease of managing warfarin in terms of keeping people in range. There are some patients who are quite steady in their INR control and other patients who are quite brittle for various reasons. Therefore， I think it is an individualized risk to benefit assessment that must be made. I have an easier time in a compliant elderly patient with serious thromboembolic disease leaving them on long-term therapy because the morbidity in that population with recurrent events can be more severe as opposed to younger patients who I prefer to give another chance before committing them to long-term anticoagulation therapy for many years.

Prof. Bauer：我们必须对患者进行个体化评估。像所有的患者，老人有某些不同的特征，使他们可能更需要预防静脉血栓栓塞性疾病（VTE）。我有一些患者并非按指南所说的那样，因为指南主要基于随机研究，这些患者很容易通过华法林控制，同时也有较高的出血风险。这取决于患者的临床特征包括临床事件的性质和严重程度。例如，如果是肺栓塞，这比深静脉血栓形成（DVT）更严重，如果患者有心肺疾病，发生临床事件时情况会更差。这些问题，可能会影响预防策略。因此，可以肯定血栓栓塞风险与个人临床危险因素有关。

至于出血的风险，年龄显然是一个因素，但还有许多临床合并症使得老年患者有更高的出血风险。 如曾经发生过出血事件，贫血及慢性肾功能不全患者出血风险更高。也许最重要的是依从性和华法林易于管理。有些患者病情十分稳定，而另外一些患者由于各种原因导致病情易变。因此，我认为考虑个体风险对评估有益。对于有严重血栓栓塞疾病的但依从性好的老年患者，我会进行长期治疗，因为和年青人相比，这些患者血栓复发事件更严重。对于较年轻的患者我会先进行抗凝治疗以决定是否给予长期抗凝治疗。

International Circulation: Men appear to have an increased risk of recurrent venous thrombosis compared to women. What new progress has been made on this aspect?

国际循环：和女性相比，男性发生静脉血栓的风险更高。这方面有新的研究进展吗？

Prof. Bauer: There has not been any progress in terms of mechanisms， which is perhaps the most interesting part of this situation. It is a paradox in some ways because women certainly have exposures， particularly when they are younger， to estrogen containing medications， which increase thromboembolic risk， and pregnancy but even when you adjust for those factors men appear to be more predisposed. Particularly older men seem more predisposed not only to first events but also to recurrences. At this time we do not know why this is the case. The data is fairly robust although the magnitude of the effect varies from study to study. An Austrian venous thrombosis study showed a rather profound effect in terms of recurrence risk but most other studies have shown it to be more modest in terms of male to female recurrences.

Prof. Bauer: 在机制方面没有取得任何进展，这也许是最有吸引力的研究领域。同时在某些方面也存在矛盾，因为女性，特别是年青女性，常常会有暴露于雌激素药物的机会，而这会增加血栓栓塞风险。此外孕妇也是，但即使调整了这些因素，男性仍更易于发生静脉血栓。尤其是老年男性似乎更易于发生首次血栓事件和复发事件。我们不知道为什么会这样。相关的研究资料很多，虽然在影响程度方面存在差异。一项奥地利静脉血栓形成的研究显示，男性比女性复发风险高得多，但其它多数研究表明男性复发风险中等升高。

International Circulation: Recently， there have been reports that the LMWH nadroparin inhibits early tumor associated angiogenesis and affects microvessel maturation. What about your opinion and what is the possible mechanism?

国际循环：最近有报道称，低分子肝素那屈肝素可抑制肿瘤早期血管生成，并影响微血管成熟。你对此怎么看，可能的机制是什么？

Prof. Bauer: There has been great interest for many years in the potential for anticoagulants to interfere with tumor growth and particularly issues with metastatic disease. Obviously， coagulation is involved in tumor implantation and angiogenesis. This is not only limited to heparins and there is some quite old data on warfarin and vitamin k antagonists having antiproliferative effects on tumors. At the ISTH congress the most rigorous trial of nadroparin for heparins as an adjunct to standard therapy for cancer to improve survival was presented. This trial was conducted in patients with prostate cancer， lung cancer， and pancreatic cancer. In this study of 503 patients， half of he group was place on LMWH and they could not find a statistically significant survival advantage. There have been trials before showing a modest effect but they have all been criticized on methodological issues. This will dampen some of the enthusiasm for using LMWH for that reason. There is a lot of information coming out in terms of using anticoagulants to prevent thrombotic complications and the morbidity of thrombotic complications. There have been several positive trials in the last year in terms of using prophylactic doses of LMWH to prevent thrombosis.

Prof. Bauer: 多年来研究人员对于抗凝剂干扰肿瘤生长，尤其转移等相关问题的研究很感兴趣。显然，凝血参与了肿瘤植入和血管生成。这不仅仅限于肝素，很早就有关于华法林和维生素K拮抗剂对肿瘤增殖有影响的研究资料。在ISTH大会上，一项临床试验显示那屈肝素可以提高癌症患者存活率。这项试验是在前列腺癌，肺癌，胰腺癌患者中进行的。该研究共选入503例患者，一半患者给予低分子量肝素，但并没有发现显著的统计学生存优势。以前也有试验显示有中等影响，但都被批评存在方法学问题。这可能会影响使用低分子量肝素的热情。目前有很多关于使用抗凝血剂预防血栓并发症及其发生率的研究资料。在去年已有一些关于使用预防剂量低分子肝素预防血栓形成的阳性研究。

International Circulation: Now many clinical doctors and guidelines