Sette H, Hughes R D, Langley P G, Gimson A E, Williams R
Thromb Haemost. 1985 Oct 30;54(3):591-4.
Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t 1/2 = 27.8 +/- 2.9 min compared to t 1/2 = 50.2 +/- 2.7 min in normal controls p less than 0.001) or by the whole blood activated clotting time (t 1/2 = 23.7 +/- 2.2 min compared to t 1/2 = 37.0 +/- 2.0 min p less than 0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 +/- 0.05 u/ml and in controls = 0.69 +/- 0.04 u/ml, p less than 0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 +/- 0.011 sec/unit, in controls 0.033 +/- 0.003 sec/unit, p less than 0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.
肝病患者由于凝血系统异常而有出血风险，尽管在需要血液透析或血液灌流时必须进行抗凝治疗。首选的抗凝剂是肝素。在本研究中，我们调查了暴发性肝衰竭（FHF）患者单次静脉注射肝素（2500单位）后的肝素动力学，发现无论通过其抗Xa效应（t 1/2 = 27.8 +/- 2.9分钟，而正常对照为t 1/2 = 50.2 +/- 2.7分钟，p小于0.001）还是通过全血活化凝血时间（t 1/2 = 23.7 +/- 2.2分钟，而对照为t 1/2 = 37.0 +/- 2.0分钟，p小于0.001）来测量，肝素的清除率均增加。通过抗Xa效应测量的肝素峰值水平降低（FHF中的峰值水平 = 0.48 +/- 0.05 u/ml，对照中为0.69 +/- 0.04 u/ml，p小于0.02），但对肝素的敏感性增加（FHF中的敏感性 = 0.072 +/- 0.011秒/单位，对照中为0.033 +/- 0.003秒/单位，p小于0.001）。FHF患者的抗凝血酶III（AT III）水平非常低，但这与肝素效应或清除的任何参数之间均无相关性。在一组慢性肝病患者中，尽管AT III水平较低，但肝素动力学与对照无差异。FHF中肝素动力学的变化可能很复杂，作为辅因子的蛋白质（如AT III）和具有肝素中和活性的蛋白质之间的平衡控制着添加肝素的反应。
