Despotis G J, Levine V, Joist J H, Joiner-Maier D, Spitznagel E
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Anesth Analg. 1997 Sep;85(3):498-506. doi: 10.1097/00000539-199709000-00005.
This study was designed to determine if, and to what extent, antithrombin III (AT) levels affect the response of the activated clotting time (ACT) to heparin in concentrations used during cardiac surgery, and to characterize the relationship between AT levels and markers of activation of coagulation during cardiopulmonary bypass (CPB). After informed consent, blood specimens obtained from eight normal volunteers (Phase I) were used to measure the response of the kaolin and celite ACT to heparin after in vitro addition of AT (200 U/dL) and after dilution with AT-deficient plasma to yield AT concentrations of 20, 40, 60, 80, and 100 U/dL. In Phase II, blood specimens collected before the administration of heparin and prior to discontinuation of CPB, were used to measure the response of the kaolin ACT to heparin (preheparin only), AT concentration, and a battery of coagulation assays in 31 patients undergoing repeat or combined cardiac surgical procedures. In Phase I, strong linear relationships were observed between kaolin (slope = 1.04 AT - 2, r2 = 0.78) and celite (slope = 1.36 AT + 6, r2 = 0.77) ACT slopes and AT concentrations below 100 U/dL. In the pre-CPB period of Phase II, only factors V (partial r = -0.49) and VIII (partial r = -0.63) were independently associated with heparin-derived slope using multivariate analysis; an inverse relationship was observed between AT and fibrinopeptide A levels (r = -0.41) at the end of CPB. Our findings indicate that the responsiveness of whole blood (ACT) to heparin at the high concentrations used with CPB is progressively reduced when the AT concentration decreases below 80 U/dL. Because AT is variably, and sometimes extensively, reduced in many patients before and during CPB, AT supplementation in these patients might be useful in reducing excessive thrombin-mediated consumption of labile hemostatic blood components, excessive microvascular bleeding, and transfusion of blood products.
Heparin, a drug with anticoagulant properties, is routinely given to patients undergoing cardiac surgery to prevent clot formation within the cardiopulmonary bypass circuit. However, when levels are reduced, heparin is not as effective. Findings within this study indicate that administration of antithrombin III may help to preserve the hemostatic system during cardiopulmonary bypass.
本研究旨在确定抗凝血酶III（AT）水平是否以及在何种程度上影响心脏手术中使用的肝素浓度下活化凝血时间（ACT）的反应，并描述体外循环（CPB）期间AT水平与凝血激活标志物之间的关系。在获得知情同意后，从8名正常志愿者（第一阶段）采集的血样用于在体外添加AT（200 U/dL）后以及用缺乏AT的血浆稀释以产生20、40、60、80和100 U/dL的AT浓度后，测量高岭土和硅藻土ACT对肝素的反应。在第二阶段，在31例接受再次或联合心脏手术的患者中，采集肝素给药前和CPB停止前的血样，用于测量高岭土ACT对肝素的反应（仅预肝素）、AT浓度以及一系列凝血试验。在第一阶段，观察到低于100 U/dL的AT浓度与高岭土（斜率 = 1.04AT - 2，r2 = 0.78）和硅藻土（斜率 = 1.36AT + 6，r2 = 0.77）ACT斜率之间存在强线性关系。在第二阶段的CPB前期，使用多变量分析仅发现因子V（偏相关系数 = -0.49）和因子VIII（偏相关系数 = -0.63）与肝素衍生斜率独立相关；在CPB结束时观察到AT与纤维蛋白肽A水平之间呈负相关（r = -0.41）。我们的研究结果表明，当AT浓度降至80 U/dL以下时，全血（ACT）对CPB中使用的高浓度肝素的反应性会逐渐降低。由于许多患者在CPB前和期间AT会有不同程度的降低，有时甚至会大幅降低，因此在这些患者中补充AT可能有助于减少凝血酶介导的不稳定止血血液成分的过度消耗、微血管过度出血以及血液制品的输注。
肝素是一种具有抗凝特性的药物，常用于心脏手术患者以防止体外循环回路内形成血栓。然而，当水平降低时，肝素的效果不佳。本研究结果表明给予抗凝血酶III可能有助于在体外循环期间维持止血系统。
