Department of Biomedical Engineering, Oregon Health & Science University School of Medicine, 3303 Southwest Bond Avenue, CH13B, Portland, OR 97239, USA.
Sci Transl Med. 2010 Jun 23;2(37):37ra45. doi: 10.1126/scitranslmed.3000697.
Most heart attacks and strokes are caused by blood clots (thrombi) that block the vasculature. Because disease-causing arterial thrombosis depends on blood platelets, platelet inhibitors such as aspirin and clopidogrel effectively decrease the risk of thrombosis; however, they also impair platelet-dependent hemostasis that staunches bleeding from wounds and can therefore produce excessive bleeding. Experimental studies show that a reduction in the number of platelets also inhibits thrombosis, but these treatments also interfere with platelet function. Because normal hemostasis requires that the platelet concentration remain within a physiological range in the circulation, we evaluated whether lowering the number of circulating platelets--but only to a value still within the normal range--by inhibiting platelet formation in the bone marrow inhibits acute thrombogenesis in baboons. We reduced the platelet count with an inhibitor against the megakaryocyte-promoting hormone thrombopoietin and then showed that experimental occlusive thrombogenesis on collagen-coated vascular grafts was reduced, without impairment of primary hemostasis. These results suggest that suppressing platelet production without interfering with the hemostatic function of platelets may offer a safe alternative to current therapies for prevention of stroke and heart attack triggered by blood clotting.
大多数心脏病发作和中风都是由阻塞血管的血栓（血栓）引起的。由于导致动脉血栓形成的是血小板，因此像阿司匹林和氯吡格雷这样的血小板抑制剂可以有效降低血栓形成的风险；然而，它们也会损害血小板依赖的止血功能，从而导致伤口出血不止，并因此产生过度出血。实验研究表明，减少血小板数量也可以抑制血栓形成，但这些治疗方法也会干扰血小板功能。由于正常的止血功能需要血小板浓度在循环中保持在生理范围内，我们评估了通过抑制骨髓中血小板的形成来降低循环血小板数量（但仅降低到正常范围内）是否可以抑制狒狒的急性血栓形成。我们用一种针对巨核细胞促进激素血小板生成素的抑制剂来降低血小板计数，然后表明，在胶原涂层血管移植物上的实验性闭塞性血栓形成减少了，而不会损害初级止血功能。这些结果表明，抑制血小板生成而不干扰血小板的止血功能可能为预防由血栓形成引起的中风和心脏病发作提供一种安全的替代当前疗法。
