Only severe thrombocytopenia results in bleeding and defective thrombus formation in mice
Only severe thrombocytopenia results in bleeding and defective thrombus formation in mice
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DOI：
10.1182/blood-2012-10-461459
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发表时间：
2013-06-13
期刊：
影响因子：
20.3
通讯作者：
Nieswandt, Bernhard
中科院分区：
文献类型：
--
作者：
Morowski, Martina;Voegtle, Timo;Nieswandt, Bernhard
血小板是止血和血栓形成的重要介质。人类血小板计数（PCs）平均为250个血小板/nL，但血小板计数如何影响止血和血栓事件的发生尚不完全清楚。小鼠的血小板含量接近1000血小板/nL，被广泛用于（病理）生理学上评估血小板功能，但在该物种中，血小板对止血和血栓性疾病的意义尚未确定。我们通过血小板消耗抗体将小鼠的PCs降低到0 - 1000血小板/nL的范围内，并在不同的动脉血栓形成模型中挑战它们：短暂性大脑中动脉闭塞（tMCAO）中风模型和尾出血实验。我们发现，当PCs分别减少70%或80%时，受损主动脉和颈动脉的血栓闭塞部分受损。相比之下，尾出血次数和小动脉血栓形成在很大程度上不受PC降低高达97.5%的影响。同样，tMCAO后的梗死生长和神经功能缺损不受PCs减少高达90%的影响，而进一步减少则具有保护作用。这些结果表明，小鼠动脉血栓形成、脑梗死和止血在出乎意料的低PCs时有效发生，这可能对具有血栓性或出血性疾病风险的人类有影响。
Platelets are essential mediators of hemostasis and thrombosis. Platelet counts (PCs) in humans average 250 platelets/nL, but it is not entirely clear how platelet numbers affect hemostasis and occurrence of thrombotic events. Mice, displaying PCs of similar to 1000 platelets/nL, are widely used to assess platelet function in (patho-) physiology, but also in this species, the significance of PC for hemostasis and thrombotic disease is not established. We reduced PCs in mice to defined ranges between 0 and 1000 platelets/nL by platelet-depleting antibodies and challenged them in different arterial thrombosis models: the transient middle cerebral artery occlusion (tMCAO) stroke model and tail bleeding experiments. We show that thrombotic occlusion of the injured aorta and the carotid artery were partially impaired when PCs were reduced by 70% or 80%, respectively. In contrast, tail bleeding times and thrombus formation in small arterioles were largely unaffected by reductions of PC up to 97.5%. Similarly, infarct growth and neurological deficits after tMCAO were unaffected by reductions of PCs up to 90%, whereas a further reduction was protective. These results reveal that arterial thrombosis, cerebral infarction, and hemostasis in mice efficiently occur at unexpectedly low PCs, which may have implications for humans at risk of thrombotic or hemorrhagic disease.