Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; and.
Blood. 2013 Nov 28;122(23):3818-24. doi: 10.1182/blood-2013-05-499384. Epub 2013 Jul 29.
The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Müller et al has been cited >100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of <10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.
最近有观点认为，血小板通过释放多聚磷酸盐激活了凝血的固有途径，这被认为是止血研究的一个突破。在短短 3 年多的时间里，Müller 等人的原始出版物被引用了>100 次。然而，没有一篇引用文章试图独立验证这一可能具有颠覆性的概念。为此，我们进行了广泛的体外和体内实验，试图验证这样一种观点，即凝血因子 XII（FXII）主要被激活的血小板所激活。与最初的断言相反，血小板衍生的多聚磷酸盐被发现是 FXII 的弱激活剂，与相当浓度的高岭土相比，FXIIa 的生成活性<10%。通过不同的凝血测定，表明血小板对全血凝固的贡献与体外 FXII 的激活生成无关。此外，发现用于体内验证原始研究假设的关键结果是不可重现的。我们的结论是，血小板衍生的多聚磷酸盐不是 FXII 的生理相关激活剂。
