Prisco D, Paniccia R, Gensini G F, Coppo M, Colella A, Filippini M, Brunelli T, Abbate R, Neri Serneri G G
Clinica Medica I, University of Florence, Italy.
Haemostasis. 1993 Nov-Dec;23(6):308-13. doi: 10.1159/000216893.
The present study was designed to investigate whether medium-term, low-dose heparin treatment is able to affect the fibrinolytic system. In a randomized cross-over study 10 asymptomatic patients with previous (1-6 years) myocardial infarction underwent two sequential 15-day treatments, respectively, on heparin and on placebo (saline solution), preceded and separated by 10-day wash-out periods. Heparin (as calcium heparin, 12,500 IU in 0.5 ml) and saline (0.5 ml) were subcutaneously administered once a day at 8 a.m. Blood samples for fibrinolysis studies were withdrawn on the first and 15th day of each period immediately before and 4 h after heparin or saline administration before and after 10 min venous occlusion (VO) respectively. Four hours after the first heparin administration tissue plasminogen activator antigen (t-PA ag) levels significantly increased with respect to saline administration (p < 0.01 and p < 0.05, respectively). After 15-day heparin treatment a decrease in euglobulin lysis time (p < 0.05) and an increase in t-PA activity (act) (p < 0.05) and in t-PA ag (p < 0.01) in comparison with placebo were observed before VO. No statistically significant changes in plasminogen activator inhibitor-1 (PAI-1) levels were found. The variations of fibrinolytic system activity induced by heparin treatment were more marked when evaluated after VO. These results indicate that medium-term low-dose heparin treatment increases t-PA ag formation and/or release with consequent t-PA act increase.
本研究旨在调查中期、低剂量肝素治疗是否能够影响纤溶系统。在一项随机交叉研究中,10名有过(1 - 6年)心肌梗死病史的无症状患者分别接受了两个连续15天的治疗,先使用肝素治疗,后使用安慰剂(生理盐水)治疗,两次治疗之间间隔10天的洗脱期。肝素(以肝素钙形式,0.5 ml含12,500 IU)和生理盐水(0.5 ml)均于每天上午8点皮下注射一次。在每个治疗期的第1天和第15天,分别在肝素或生理盐水给药前即刻以及给药后4小时、静脉闭塞(VO)10分钟前后采集用于纤溶研究的血样。首次给予肝素4小时后,组织纤溶酶原激活物抗原(t - PA ag)水平相对于给予生理盐水时显著升高(分别为p < 0.01和p < 0.05)。在15天肝素治疗后,与安慰剂相比,观察到优球蛋白溶解时间缩短(p < 0.05),t - PA活性(act)升高(p < 0.05)以及t - PA ag升高(p < 0.01),此时尚未进行VO。未发现纤溶酶原激活物抑制剂 - 1(PAI - 1)水平有统计学意义的变化。当在VO后进行评估时,肝素治疗引起的纤溶系统活性变化更为明显。这些结果表明,中期低剂量肝素治疗可增加t - PA ag的形成和/或释放,从而导致t - PA act升高。