Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.
PLoS One. 2013 May 28;8(5):e64112. doi: 10.1371/journal.pone.0064112. Print 2013.
Recurrent bleeding can complicate the treatment of thrombosis patients with vitamin K antagonists (VKA), even at a well-regulated level of anticoagulation. In this proof-of-principle study, we investigated whether alterations in platelet function or von Willebrand factor (vWf) contribute to a bleeding phenotype in these patients.
In this case-control study 33 well-regulated patients without bleeding events (controls) and 33 patients with recurrent bleeding (cases) were retrospectively included. Thrombin generation and vWf were determined in plasma. Platelet function was assessed by light transmission aggregometry and flow cytometry using a validated panel of agonists.
Thrombin generation was similarly reduced in controls and cases, in comparison to normal plasma. Plasma vWf level was above the normal range in 85% of controls and 67% of the cases. vWf activity was similarly increased in all patients in comparison to healthy volunteers. Platelet aggregation was in the normal range for almost all patients irrespective of the type of agonist. However, in response to a low collagen dose, platelets from 21% of controls and 27% of cases showed diminished responses. Agonist-induced secretion of alpha- and dense-granules or integrin αIIbβ3 activation were affected in platelets from neither controls nor cases.
Recurrent bleeding in well-controlled patients on VKA therapy is not explained by anti-hemostatic changes in platelet or vWf function.
即使在抗凝作用得到很好控制的情况下，维生素 K 拮抗剂（VKA）治疗的血栓患者也可能会出现反复出血，从而使治疗变得复杂。在这项原理验证研究中，我们研究了血小板功能或血管性血友病因子（vWf）的改变是否导致这些患者出现出血表型。
本病例对照研究回顾性纳入了 33 例未发生出血事件的病情稳定患者（对照组）和 33 例反复出血患者（病例组）。在血浆中测定凝血酶生成和 vWf。通过使用经验证的激动剂组合的光传输聚集度和流式细胞术评估血小板功能。
与正常血浆相比，对照组和病例组的凝血酶生成均明显降低。85%的对照组和 67%的病例组的血浆 vWf 水平高于正常范围。与健康志愿者相比，所有患者的 vWf 活性均明显增加。几乎所有患者的血小板聚集均在正常范围内，无论激动剂的类型如何。然而，对于低浓度的胶原，对照组中有 21%的患者和病例组中有 27%的患者的血小板反应减弱。无论是对照组还是病例组，血小板对激动剂诱导的α-和致密颗粒分泌或整合素αIIbβ3激活的反应均未受到影响。
在接受 VKA 治疗且病情得到很好控制的患者中，反复出血不能用血小板或 vWf 功能的抗凝血变化来解释。
