Abstract：
OBJECTIVE: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis.
METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 μg/daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher\'s exact test or Pearson\'s Chi-Squared test.
RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events.
CONCLUSIONS: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.
METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 μg/daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher\'s exact test or Pearson\'s Chi-Squared test.
RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events.
CONCLUSIONS: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.
摘要：
目的：接受透析治疗的患者维生素K功能状态较差，这可能会增加血管钙化的风险。因此，补充维生素K可能与透析患者有关，但促凝作用尚未研究。我们评估了补充甲基萘醌-7（MK-7）对透析患者凝血生物标志物的影响。
方法：双盲，安慰剂对照研究对123例透析患者进行随机分配至52周的维生素K（MK-7，360μg/天，n=61）或安慰剂（n=62）。基线和干预52周后的测量包括凝血酶生成（内源性凝血酶电位（ETP），凝血酶峰值浓度,时间达到顶峰，和滞后时间)，维生素K依赖性凝血因子的凝块活性（F）II，VII,IX,X,凝血酶原片段1+2(F1+2),和维生素K缺乏II（PIVKA-II）诱导的蛋白质。组间差异（维生素K与安慰剂）在52周时进行协方差分析。用配对t检验分析维生素K组和安慰剂组的组内变化。根据医院记录记录血管不良事件（AE）和严重不良事件（SAE）。实验室数据,和参与者访谈，并使用Fisher精确检验或Pearson卡方检验进行组间比较。
结果：在52周时观察到PIVKA-II的组间差异（p<0.001）。维生素K组PIVKA-II从基线到52周显著下降，但安慰剂组没有。我们没有观察到组间差异或组内凝血生物标志物的变化，除了FVII凝块活性在安慰剂组中降低（p=0.04），AE和SAE没有组间差异。
结论：透析患者补充维生素K一年对凝血激活的生物标志物没有检测到的影响，维生素K依赖性凝血因子的凝块活性，血管事件或死亡，表明这种治疗没有促凝血作用。
方法：双盲，安慰剂对照研究对123例透析患者进行随机分配至52周的维生素K（MK-7，360μg/天，n=61）或安慰剂（n=62）。基线和干预52周后的测量包括凝血酶生成（内源性凝血酶电位（ETP），凝血酶峰值浓度,时间达到顶峰，和滞后时间)，维生素K依赖性凝血因子的凝块活性（F）II，VII,IX,X,凝血酶原片段1+2(F1+2),和维生素K缺乏II（PIVKA-II）诱导的蛋白质。组间差异（维生素K与安慰剂）在52周时进行协方差分析。用配对t检验分析维生素K组和安慰剂组的组内变化。根据医院记录记录血管不良事件（AE）和严重不良事件（SAE）。实验室数据,和参与者访谈，并使用Fisher精确检验或Pearson卡方检验进行组间比较。
结果：在52周时观察到PIVKA-II的组间差异（p<0.001）。维生素K组PIVKA-II从基线到52周显著下降，但安慰剂组没有。我们没有观察到组间差异或组内凝血生物标志物的变化，除了FVII凝块活性在安慰剂组中降低（p=0.04），AE和SAE没有组间差异。
结论：透析患者补充维生素K一年对凝血激活的生物标志物没有检测到的影响，维生素K依赖性凝血因子的凝块活性，血管事件或死亡，表明这种治疗没有促凝血作用。
