Lip G Y, Lip P L, Zarifis J, Watson R D, Bareford D, Lowe G D, Beevers D G
Department of Medicine, City Hospital, Birmingham, England, UK.
Circulation. 1996 Aug 1;94(3):425-31. doi: 10.1161/01.cir.94.3.425.
Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF.
We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P < .001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels.
Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.
既往研究表明，房颤（AF）患者的血栓形成标志物增加，提示存在高凝或血栓前状态。本研究的目的是确定引入超低剂量华法林（1毫克）、传统华法林和阿司匹林（300毫克）治疗对房颤患者血栓形成和血小板活化的影响。
我们测量了51例慢性房颤患者在随机接受1毫克华法林或300毫克阿司匹林治疗前、治疗后2周和6周时血浆纤维蛋白D - 二聚体（血栓形成指标）和β - 血小板球蛋白（β - TG，血小板活化指标）的连续变化（第1阶段）。然后所有患者开始接受传统华法林治疗（第2阶段），并在2周和6周后采集样本。将治疗前结果与26例窦性心律健康对照者的结果进行比较。房颤患者的基线（治疗前）β - TG和D - 二聚体水平高于对照者（P <.001）。在第1阶段，尽管使用了1毫克华法林或300毫克阿司匹林，纤维蛋白D - 二聚体或β - TG的中位数水平没有显著变化。使用标准华法林治疗（第2阶段）时，与基线水平相比，6周时β - TG中位数降低（P =.025），2周（P =.001）和6周（P <.001）时D - 二聚体中位数水平连续降低。
与窦性心律患者相比，房颤患者的血管内血栓形成和血小板活化增加。引入超低剂量华法林（1毫克）或300毫克阿司匹林不会显著改变这些标志物，尽管传统华法林治疗可降低β - TG和纤维蛋白D - 二聚体水平。这与全剂量华法林在预防房颤患者中风和血栓栓塞方面的有益作用一致，并表明超低剂量华法林和阿司匹林可能不会发挥类似的有益作用。
