Henny C P, Ten Cate H, Ten Cate J W, Moulijn A C, Sie T H, Warren P, Büller H R
J Lab Clin Med. 1985 Aug;106(2):187-96.
Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated.
术后出血仍然是体外循环（CPB）手术中的一种严重并发症。在我们的研究中，将一种新型低分子量（LMW）类肝素（Org 10172）的替代抗凝方案与标准化肝素方案进行了比较。一项初步的剂量探索性研究表明，类肝素的最小有效剂量为260抗Xa单位/千克体重，这与标准化肝素方案相当，血浆抗Xa值相似即表明了这一点。接下来在12只接受CPB的杂种犬中进行的随机开放先导研究表明，类肝素与肝素一样有效，Org 10172组术后失血量还有额外的有利减少。我们在16只接受CPB的杂种犬中进行了随机盲法研究以证实先前的结果。两种抗血栓药物在预防体外循环回路内血栓形成方面均有效。血细胞比容值以及红细胞和血小板计数显示组间无显著差异。CPB后白细胞计数显示，给予类肝素的组升高明显更快（P小于0.05）。在给予肝素的组中，观察到凝血酶时间（TT）和活化部分凝血活酶时间（APTT）均出现预期的延长，而在给予类肝素的组中，仅在给药后TT出现短暂的峰值延长，APTT无显著延长。CPB期间平均血浆抗Xa水平相似，在给予肝素的组中，给予鱼精蛋白后抗Xa水平迅速下降，APTT也是如此。术野评估表明，给予肝素的组术中失血量增加。在胸腔关闭后2.5小时内测量的术后失血量，给予类肝素的组明显低于肝素化动物组（分别为625±100.0毫升，平均值±标准差，和806±178.2毫升；P小于0.05）。我们的观察结果表明，低分子量类肝素Org 10172与标准肝素相比具有更高的效益/风险比，并且在犬类CPB中有效。在人类中进行的进一步研究应验证在肝素相对禁忌的患者中使用这种物质作为CPB期间替代抗凝手段的可能性。
