Dehmer G J, Lange R A, Tate D A, Pirwitz M, Daniel W, Fisher M, Bonnem E M
Cardiac Catheterization Laboratories, University of North Carolina Hospitals, Chapel Hill 27514, USA.
Circulation. 1996 Nov 1;94(9 Suppl):II347-52.
Protamine reverses heparin anticoagulation, but it can have important side effects. We compared the safety and effectiveness of intravenous recombinant platelet factor 4 (rPF4) as an alternative to protamine in a randomized blinded trial.
In 81 patients having diagnostic cardiac catheterization, baseline hemodynamics were measured after a 5000-U bolus of heparin. Repeat measurements were obtained at the end of the procedure, and the anticoagulation status was determined by an activated coagulation time (ACT) and activated partial thromboplastin time (aPTT). Patients then received either protamine (50 mg IV over 10 minutes) or rPF4 (1.0 mg/kg IV over 2 minutes) in a blinded fashion. Serial measurements of hemodynamic and clotting functions were performed 5, 10, 20, and 30 minutes after drug administration. Follow-up measurements and clinical assessments were made at 1, 4, 6, and 24 hours later and after 7 days. Before drug administration, ACTs, aPTTs, and hemodynamics were similar among the groups. After drug infusion, there was no difference in ACT between the protamine and rPF4 patients. At 20 and 30 minutes after drug infusion, ACT and aPTT were slightly higher in those receiving rPF4, but these changes were small and of no clinical significance. There were no clinically meaningful differences in any of the hemodynamic variables between the groups, and there were no serious side effects in any patient.
At the dose used in this study, rPF4 was well tolerated and reversed the anticoagulant effect of heparin. These data support its continued evaluation as an alternative to protamine after cardiac surgery.
鱼精蛋白可逆转肝素抗凝作用，但可能有重要的副作用。我们在一项随机双盲试验中比较了静脉注射重组血小板因子4（rPF4）作为鱼精蛋白替代品的安全性和有效性。
81例接受诊断性心导管检查的患者，在静脉注射5000 U肝素推注后测量基线血流动力学。在手术结束时重复测量，并通过活化凝血时间（ACT）和活化部分凝血活酶时间（aPTT）确定抗凝状态。然后患者以盲法接受鱼精蛋白（10分钟内静脉注射50 mg）或rPF4（2分钟内静脉注射1.0 mg/kg）。在给药后5、10、20和30分钟进行血流动力学和凝血功能的系列测量。在1、4、6和24小时后以及7天后进行随访测量和临床评估。给药前，各组间的ACT、aPTT和血流动力学相似。给药后，鱼精蛋白组和rPF4组患者的ACT无差异。在给药后20和30分钟，接受rPF4的患者的ACT和aPTT略高，但这些变化很小且无临床意义。两组间任何血流动力学变量均无临床意义上的差异，且任何患者均无严重副作用。
在本研究使用的剂量下，rPF4耐受性良好，并逆转了肝素的抗凝作用。这些数据支持其作为心脏手术后鱼精蛋白替代品继续进行评估。
