Ribeiro A A, Lourenço D M, Toledo C F, Noguti M A, Borges D R
Disciplina de Hematologia, Universidade Federal de São Paulo, Escola Paulista de Medicina.
Rev Assoc Med Bras (1992). 1997 Jul-Sep;43(3):189-94. doi: 10.1590/s0104-42301997000300004.
Patients with severe hepatic failure present acquired deficiency of antithrombin III (ATIII) owing to reduced synthesis associated with intravascular activation of blood coagulation, which may be corrected by ATIII infusion.
The aim of this uncontrolled trial was to verify the effect of a standard dose of ATIII concentrate (Kybernin), that is, 50 U/kg of body weight per day, every 2 days, on ATIII levels in patients with severe hepatic failure and hemostatic imbalance.
Six cirrhotic patients were studied: mean age of 44 years (14 to 63 years), who presented at least 2 abnormal coagulation tests (PT > 1.40, APTT > 1.25, Fibrinogen < 1.5 g/dL, Platelet count < 80,000/mm3). Mean serum albumin was 2.6 g/dL (1.9 to 3.8 g/dL). Blood was drawn before infusion, 4 h after the first infusion, and just before the next infusion. ATIII levels were measured by amidolytic method.
Mean ATIII levels were: initial = 35.8%, 4th h = 56.2%, 2nd d = 48.7%, 4th d = 45.7%*, and 8th d = 42.3%. ATIII levels increased significantly after infusion of this standard dose in all patients, although they have not been fully corrected (Friedman test, * p < 0.02), which has been sustained till the 4th day. There was no improvement on the clinical outcome.
These findings suggest that doses of ATIII concentrate higher than 50 U/kg/infusion must be administered to patients with severe hepatic failure, to guarantee normal levels of the inhibitor, in order to verify its influence on the hemostatic mechanism.
严重肝衰竭患者因与血管内凝血激活相关的合成减少而出现抗凝血酶III(ATIII)获得性缺乏,可通过输注ATIII来纠正。
这项非对照试验的目的是验证标准剂量的ATIII浓缩物(凯贝林),即每天每公斤体重50 U,每2天一次,对严重肝衰竭和止血失衡患者ATIII水平的影响。
研究了6例肝硬化患者:平均年龄44岁(14至63岁),至少有2项凝血试验异常(PT>1.40,APTT>1.25,纤维蛋白原<1.5 g/dL,血小板计数<80,000/mm3)。平均血清白蛋白为2.6 g/dL(1.9至3.8 g/dL)。在输注前、首次输注后4小时以及下次输注前采集血液。通过酰胺水解法测量ATIII水平。
平均ATIII水平为:初始=35.8%,第4小时=56.2%,第2天=48.7%,第4天=45.7%*,第8天=42.3%。所有患者输注该标准剂量后ATIII水平均显著升高,尽管未完全纠正(Friedman检验,*p<0.02),且这种升高一直持续到第4天。临床结局无改善。
这些发现表明,对于严重肝衰竭患者,必须给予高于50 U/kg/次的ATIII浓缩物剂量,以保证抑制剂水平正常,从而验证其对止血机制的影响。