Diseases associated with arterial thrombosis or venous thrombosis are leading causes of mortality and morbidity globally. Since the 1930s, anti thrombotic therapy has been the cornerstone of medical therapy for thrombotic diseases. However, the success of anti thrombotic therapy has come at the cost of one of the most dreaded iatrogenic complications— bleeding. Recently, new evidence has emerged on potentially important differences between thrombosis and hemostasis, thereby raising the possibility of developing new anti thrombotic drugs that do not cause bleeding. All currently used antithrombotic drugs in the clinic are associated with an inherent risk of bleeding. For example, the risk of serious major bleeding with a non–vitamin K antagonist oral anticoagulant is ≈2% to 3%, with the risk of intracranial hemorrhage of ≈0.3 to 0.5% per annum.1 Likewise nonmajor bleeding with aspirin approximates 2%, and the rates of major and life-threatening bleeding rises significantly in those over 75 years of age to >2% per year.2 Thus, a significant proportion of patients at high risk of thrombotic disease are vulnerable to bleeding complications and often miss out on potentially beneficial antithrombotic therapy. Importantly, aside from the mortality and morbidity directly linked to the index bleeding event, there is a large body of evidence demonstrating that hemorrhagic complications are associated with adverse clinical outcomes.3 Despite the introduction of new anticoagulants, such as the non–vitamin K antagonist oral anticoagulants and newer antiplatelet drugs, we have reached a tipping point with regard to the achievable balance between antithrombotic potency and bleeding risk with current antithrombotic approaches. Therefore, there remains an unmet clinical need for new antithrombotic approaches that maintain efficacy while preserving hemostasis. Recently, major progress has been achieved in our understanding of the factors that may differentially regulate pathological thrombosis from hemostasis based on the introduction of intravital microscopy, …

中文翻译：

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新型抗血栓药物即将出现

与动脉血栓形成或静脉血栓形成相关的疾病是全球死亡率和发病率的主要原因。自1930年代以来，抗血栓形成治疗一直是血栓形成疾病药物治疗的基石。但是，抗血栓治疗的成功是以最令人恐惧的医源性并发症之一为代价的-出血。最近，关于血栓形成和止血之间潜在重要差异的新证据出现了，从而增加了开发不会引起出血的新型抗血栓形成药物的可能性。临床上目前使用的所有抗血栓药物均与内在的出血风险相关。例如，使用非维生素K拮抗剂口服抗凝剂导致严重大出血的风险约为每年2％至3％，而颅内出血的风险每年约为0.3％至0.5％。1同样，使用阿司匹林的非主要出血量约为2％，并且在75岁以上的老年人中，重大和威胁生命的出血率显着上升至每年> 2％。2因此，相当一部分血栓形成高危患者容易发生出血并发症，并且经常错过潜在有益的抗血栓治疗。重要的是，除了与指数出血事件直接相关的死亡率和发病率外，还有大量证据表明出血并发症与不良的临床结果有关。3尽管引入了新的抗凝剂，例如非维生素K拮抗剂口服抗凝药和新型抗血小板药，在目前的抗血栓形成方法中，抗血栓形成能力和出血风险之间可实现的平衡方面，我们已经达到了一个临界点。因此，仍然需要满足新的抗血栓形成方法的临床需求，该方法可以在保持止血的同时保持功效。最近，在引入活体显微镜的基础上，我们对可能与止血不同地调节病理性血栓形成的因素的理解取得了重大进展，…