International Circulation: As you have said in your lecture today， could you please discuss the management of heparin-induced thrombocytopenia (HIT)?

《国际循环》：如您今天在您的演讲中所言，能否请您讨论一下肝素诱导的血小板减少症 （HIT）的处理？
Prof. Bauer：HIT is an important complication of anticoagulant therapy and， of course， anticoagulants are given to people who are at risk for thrombosis or already have thrombosis. Paradoxically， when people develop HIT the heparin is actually acting as a drug that promotes thrombosis so it is a paradoxical complication of heparin therapy and antibody formation. Central to management is stopping heparin as soon as you suspect it and considering whether or not the clinical picture fits HIT. If you think that it does in terms of the degree of platelet count drop， usually more than 50% from baseline， the timing， which usually occurs after about 5 days of the new heparin exposure， the absence of other causes of thrombocytopenia， and finally the presence of thrombosis. Then you need to introduce an alternative anticoagulant therapy involving a non-heparin anticoagulant. The agents that are currently tested and approved are called Argatroban， another called Recombin Hirudin， or Lepirudin are really the acute therapies for HIT. The key is to stop heparin， make a diagnosis， and start an alternative anticoagulant is the management.

Bauer教授 ：HIT是抗凝治疗的重要并发症之一，当然，抗凝药物需要给予那些有血栓形成风险或者已有血栓的患者。但矛盾的是，当患者出现HIT时，肝素实际上是作为一种促进血栓形成的药物而发挥作用，因此这是肝素治疗的一种反常并发症，涉及到抗体的形成。处理的关键是当你怀疑这种情况存在时立即停止肝素治疗，并考虑临床情形是否符合HIT。如果根据血小板计数下降程度（通常比基线值降低超过50%）、发生时间（通常发生于新的肝素接触约5天后）、缺乏其他原因所致的血小板减少、 以及存在血栓，你认为确实符合HIT，那么你需要换用另外某种非肝素类抗凝药物。目前获得试验和批准的药物包括阿加曲班（Argatroban），重组水蛭素（Recombin Hirudin），或者来匹卢定（Lepirudin）， 它们确实是HIT的急性治疗药物。处理的关键是停止肝素治疗，做出诊断，并开始换用某种其他抗凝药物。。

International Circulation:  Thrombosis occurs in 20%~50% of patients with HIT.  What about the anticoagulant strategies for these patients?

《国际循环》：血栓发生于20%~50% HIT患者中。这些患者的抗凝策略是什么？

Prof. Bauer：There are two types of HIT， the so-called HITT， which refers to the type that when people develop HIT they already have new thromboses and obviously have to be treated. The patients with a 50% risk are those patients who have developed the platelet count drop but do not yet demonstrate new deep venous thrombosis， pulmonary emboli， or arterial complications. They have a 50% risk of developing symptomatic thrombosis within 30 days. That is the 50%. Those people need preventative anticoagulant to prevent a very high rate of thrombosis that will occur in people with HIT if they do not already have it.

Bauer教授 ：有两种类型的HIT，一是所谓的HIT，是指那种发生HIT时已有新的血栓形成的患者，他们显然必须接受治疗。有50%风险的患者则为那些已经出现血小板计数的下降，但是尚未表现出新的深静脉血栓形成、肺栓塞、或者动脉并发症。他们有50%的风险在30天内出现有症状的血栓。这是另外的 50%，这些HIT患者需要预防性抗凝治疗，从而预防可能要发生但是尚未发生的、有着极高发生率的血栓形成。

International Circulation:  Could you please talk about your experience regarding the efficacy of fondaparinux for HIT?

《国际循环》：能否请您谈论一下您在磺达肝癸钠治疗HIT的疗效方面的经验？

Prof. Bauer：There are a number of case reports where fondaparinux has been used for HIT. There are successes that are reported and from a conceptual basis fondaparinux should be a good drug for HIT but the problem is that it has not been formally studied in any large， well controlled case series to really substantiate that. It has all been small or antecdotal evidence suggesting that. I presented one case during my presentation of a patient who had HIT， very strongly postitive documentation where the patient actually developed new thrombosis despite having been treated in the standard way with atroban or warfarin. At that point when she failed with the standard therapy we placed her on fondaparinux with success. I and other have had success treating with fondaparinux although it has not yet been formally approved for HIT.  Even though it is an attractive strategy it has not yet been formally approved.

Bauer教授 ：有许多关于使用磺达肝癸钠治疗HIT的病例报告，也有这方面的成功案例，而且在理论上，磺达肝癸钠应该是对HIT有益的药物，但是问题在于，它尚未在任何大型、很好对照的病例系列中得到正式的研究，从而真正证实这一点。目前都是一些很小的或者之前的证据有所提示。我曾在演讲中介绍了一例病例，一名HIT患者有着强有力的阳性证据证明其虽然正以标准方式接受了阿加曲班或者华法林的治疗，依然出现了新的血栓形成。当她用标准治疗失败时，我们给她换用了磺达肝癸钠，并获得成功。虽然磺达肝癸钠尚未被正式批准用于HIT，但是我和其他医生都有用它治疗的成功经历。尽管应用磺达肝癸钠的策略很吸引人，但是它尚未得到正式的批准。

International Circulation:   Fondaparinux does not induce clinical HIT compared with UFH and low molecular weight heparin.  Would you please talk about the reason or mechanism?

《国际循环》：与普通肝素和低分子量肝素相比，磺达肝癸钠并不导致临床HIT。能否请您谈论一下其原因或者机制？

Prof. Bauer： From a biologic standpoint fondaparinux should not induce HIT. There is one reported case in the millions of exposures so it almost never induces HIT.   Certainly if you use fondaparinux there is not reason to monitor platelet count because it is essectionally totally absent of the complication of HIT for practical purposes.  From a mechanism point of view， the reasons are that to develop these antibodies you would need the heparin or low molecular weight heparin to interact with platelet Factor-4 because it is really that interaction where heparin binds to platelet Factor-4 that causes antibodies to be produced. That is the stimulus. There is very little interaction between fondaparinux and platelet Factor-4 since they just don’t bind to each other. They bind together so weakly that you don’t form the complexes that can elicit the immune response， which is the reason why fondaparinux does not induce HIT.  

Bauer教授 ： 从生物学的角度，磺达肝癸钠不应导致HIT。在数百万接触磺达肝癸钠的患者中只有一例见诸报告，所以它几乎从不导致HIT。当然，如果使用磺达肝癸钠，也没有需要监测血小板计数的理由，因为基本没有HIT的并发症。从机制角度，原因在于这些抗体的产生需要肝素或者低分子量肝素与血小板因子-4（PF-4）相互作用，因为确实是肝素结合于PF-4的相互作用导致了抗体的产生。这就是刺激。磺达肝癸钠与PF-4之间的相互作用极小，原因很简单，它们之间不会结合，它们结合在一起的作用力很弱，不会形成可以引起免疫反应的复合物，这就是磺达肝癸钠不会导致HIT的原因。