Shigeta O, Kojima H, Hiramatsu Y, Jikuya T, Terada Y, Atsumi N, Sakakibara Y, Nagasawa T, Mitsui T
Division of Cardiovascular Surgery, Insitute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
J Thorac Cardiovasc Surg. 1999 Aug;118(2):354-60. doi: 10.1016/S0022-5223(99)70227-8.
The heparin-protamine titration method that uses the Hepcon hemostasis management system (Medtronic HemoTec Inc, Englewood, Colo) reduced blood loss in cardiac surgery in previous reports, but the mechanism is not fully understood. This study tests the hypothesis that reduced protamine administration preserves platelet function in human cardiac surgery.
Platelet count, alpha-granule secretion, and aggregation to thrombin before and after cardiopulmonary bypass in human beings were evaluated. In the control group (n = 14), a fixed dose of protamine (3 mg/kg) was administered. In the titration group (n = 20), protamine doses were based on the heparin concentration measured by the Hepcon system.
Heparin concentrations before protamine administration were higher in the titration group (P =.0012), but protamine doses of patients in the titration group were markedly lower than those of the control group (P <.0001). During protamine infusion at a rate of 0.3 mg. kg(-1). min(-1), the percentage of granule membrane protein-140-positive platelets significantly increased in the control group compared with the titration group (18.8% +/- 8.6% vs 13.0% +/- 5.3%, P =.0188). After protamine administration, aggregation of washed platelets to thrombin recovered almost to the preoperative level in the titration group; however, it remained lower in the control group (20% +/- 20% vs 55% +/- 18%, P =.0009).
Low-dose administration of protamine, based on a heparin-protamine titration method, restores not only the blood coagulation but also the platelet responses to thrombin and attenuates platelet alpha-granule secretion during heparin neutralization. Overdose of protamine activates platelets and may predispose patients to excessive bleeding after cardiac surgery.
先前的报告显示，使用Hepcon止血管理系统（美敦力血液技术公司，科罗拉多州恩格尔伍德）的肝素-鱼精蛋白滴定法可减少心脏手术中的失血量，但其机制尚未完全明确。本研究旨在验证以下假设：在人体心脏手术中，减少鱼精蛋白的用量可保留血小板功能。
评估人体体外循环前后的血小板计数、α-颗粒分泌以及对凝血酶的聚集情况。对照组（n = 14）给予固定剂量的鱼精蛋白（3 mg/kg）。滴定组（n = 20）的鱼精蛋白剂量基于Hepcon系统测得的肝素浓度。
滴定组在给予鱼精蛋白前的肝素浓度较高（P = 0.0012），但滴定组患者的鱼精蛋白用量明显低于对照组（P < 0.0001）。在以0.3 mg·kg⁻¹·min⁻¹的速率输注鱼精蛋白期间，对照组中颗粒膜蛋白-140阳性血小板的百分比相比滴定组显著增加（18.8% ± 8.6% 对 13.0% ± 5.3%，P = 0.0188）。给予鱼精蛋白后，滴定组中洗涤后的血小板对凝血酶的聚集几乎恢复到术前水平；然而，对照组中仍较低（20% ± 20% 对 55% ± 18%，P = 0.0009）。
基于肝素-鱼精蛋白滴定法进行低剂量鱼精蛋白给药，不仅可恢复凝血功能，还可恢复血小板对凝血酶的反应，并在肝素中和过程中减弱血小板α-颗粒分泌。鱼精蛋白过量会激活血小板，并可能使患者在心脏手术后易发生过度出血。
