| Objective:Coronary artery bypass grafting (CABG) surgery is one effective means of treating coronary heart disease. However, perioperative myocardial infarction significantly reduced the rate of success of surgery. Therefore, timely and effective anticoagulant therapy was payed attention by cardiovascular surgeons. Low molecular weight heparin was recognized as one of the better anticoagulant drugs. However, reports indicate it may increase the risk of wound bleeding, pericardial tamponade and secondary thoracotomy. There was no clinical rapid and effective means of monitoring. Anti-Xa activity was now considered the gold standard for monitoring low molecular weight heparin. But it was difficult for clinical real-time monitoring, and expensive. This study was designed to find out the fast, effective and convenient means of clinical monitoring of low molecular weight heparin by monitoring anti-Xa activity and ACT and to reduce the risk of anticoagulation therapy of low molecular weight heparin. The same time,compared anti-clotting curative of two different doses'LMWH to make clear the ideal antithrombotic dose .Method: A total of 74 patients (Male 47, female 27) who had been performed off-pump coronary artery bypass grafting in cardiovascular surgery of first hospital of Qinhuangdao between February 2008 and December 2009 were enrolled and randomly divided into 2 groups in this prospective, randomized design. All three coronary artery had disease by coronary angiography. Internal mammary artery was pre-emergency. High-dose low molecular weight heparin involved 42 patients (Male 26, female 16; mean age, 60.1±9.8 years). 15 cases had a history of old myocardial infarction, 27 cases had previous angina pectoris events. Low-dose low molecular weight heparin involved 32 patients (Male 21, female 11; mean age, 59.7±9.1 years). 10 cases had a history of old myocardial infarction, 22 cases had previous angina pectoris events. Aspirin and clopidogrel were replayed by low molecular weight heparin 5000 IU subcutaneously every 12 hours from one week to 12 hour before surgery in all patients. Per hour chest drainage volume (including pericardial drainage, mediastinal drainage, the left side of chest drainage) was measured after coronary artery bypass grafting. Younishu began to be given for anticoagulation therapy if per hour the drainage volume was less than 100ml (excluding the first hour after surgery) continuously for three hours, and showed a gradual decreasing trend. Low-dose low molecular weight heparin group was given 2500IU Younishu subcutaneously every 12 hours, and High-dose low molecular weight heparin was given 5000IU Younishu subcutaneously every 12 hours. Blood samples were collected before treatment and at 1hour, 3 hours, 6 hours, 8 hours and 10 hours after drug injection respectively. Activated clotting time (ACT) was tested by activated whole blood clotting time tester. Anti-Xa activity was detected by chromogenic substrate method.Results:1 Laboratory indexes1.1 ACT values of low-dose low molecular weight heparin group were (128.81±10.19)s, (135.44±18.57)s, (141.26±12.35)s, (131.00±18.70)s, (122.41±13.35)s, (117.96±12.00)s before treatment and at 1 hours, 3 hours, 6 hour, 8 hours and 10 hours after drug injection respectively. ACT values of high-dose low molecular weight heparin group were (130.00±18.46)s, (162.44±25.57)s,(191.26±22.34)s,(149.00±23.70)s,(146.41±13.35)s,(140.96±12.00)s before treatment and at 1 hours, 3 hours, 6 hour, 8 hours and 10 hours after drug injection respectively. ACT values of two groups reached maximum at 3 hours after drug injection. T test showed that the differences between maximums of the two groups and between the maximum and the value of before treatment in every group had statistical significance (P<0.05) (table4).1.2 The values of anti-Xa activity of low-dose low molecular weight heparin group were(0.12±0.09)IU/ml, (0.27±0.11)IU/ml, (0.32±0.10)IU/ml, (0.22±0.11)IU/ml, (0.19±0.05)IU/ml, (0.15±0.07)IU/ml before treatment and at 1 hours, 3 hours, 6 hour, 8 hours and 10 hours after drug injection respectively. The values of anti-Xa activity of high-dose low molecular weight heparin group were (0.14±0.11)IU/ml,(0.67±0.09)IU/ml,(0.72±0.09)IU/ml, (0.65±0.05) IU/ml,(0.56±0.07)IU/ml, (0.49±0.07)IU/ml before treatment and at 1 hours, 3 hours, 6 hour, 8 hours and 10 hours after drug injection respectively. The values of anti-Xa activity of two groups reached maximum at 3 hours after drug injection. T test revealed that the differences between maximums of the two groups and between the maximum and the value of before treatment in every group had statistical significance (P<0.05) (table4).1.3 Only 21.88% of peak value of anti-Xa activity in low-dose low molecular weight heparin group reached the value of effective anticoagulant activity (0.50 IU/ml). No one of all values exceeded 1.00 IU/ml. 90.48% of peak value of anti-Xa activity in high-dose low molecular weight heparin group reached the value of effective anticoagulant activity.11.90% of that reached 1.00 IU/ml. This showed they had a higher tendency to bleed. The value of X2 revealed that the differences between the two groups had statistical significance (P<0.05) (table5).1.4 Correlation test of anti-Xa activity and ACT: correlation was poor. Correlation coefficient showed the differences between anti-Xa activity and ACT were statistically significant. Correlation coefficient in low-dose low molecular weight heparin group was 0.39(P<0.01)(fig.4).That in high-dose low molecular weight heparin group was 0.60(P<0.01)(fig.5).2 Clinical indexes2.1 Chest drainage volume of 24h after surgery: That in low-dose low molecular weight heparin group was 356±145ml. That in high-dose low molecular weight heparin group was 575±152ml. The differences between the two groups had statistical significance (P<0.05) (table3).2.2 Extubation time of thoracic duct after surgery: That in low-dose low molecular weight heparin group was 39.42±7.85h. That in high-dose low molecular weight heparin group was 42.12±8.72h. The differences between the two groups had statistical significance (P<0.05) (table3).2.3 3 cases of perioperative myocardial infarction after surgery taken place in the low-dose low molecular weight heparin group . 1 cases of perioperative myocardial infarction after surgery taken place in the high-dose low molecular weight heparin group , the differences between the two groups had statistical significance (P>0.05) (table6). All patients were divided into two groups. AA group: the value of anti-Xa activity was less than 0.5 IU/ml. BB group: the value of anti-Xa activity was greater than 0.5 IU/ml. The value of X2 revealed that the differences between AA group and BB group had statistical significance(P<0.05) (table7). 6 cases had secondary thoracotomy to stop bleeding: 5 cases which contained 1 bleeding of vascular anastomose and 4 wound bleeding occurred in high-dose low molecular weight heparin group.1 value of anti-Xa activity was in the range of 0.5-1.0IU/ml and 3 values of anti-Xa activity was greater than 1.0 IU/ml.1 case had secondary thoracotomy to stop bleeding in low-dose low molecular weight heparin group. The value of anti-Xa activity was less than 0.5 IU/ml. There was no active bleeding point in intraoperative exploration. All patients were divided into three groups. A group: the value of anti-Xa activity was less than 0.5 IU/ml. B group: the value of anti-Xa activity was in the range of 0.5-1.0IU/ml. C group: the value of anti-Xa activity was greater than 1.0 IU/ml. The value of X2 revealed that the differences between A group and B group had no statistical significance(P>0.05) (table 9). The value of X2 revealed that the differences between A group and C group and between B group and C group had statistical significance(P<0.05) (table9).Conclusion:1 If the value of anti-Xa activity is less than 0.5IU/ml, low molecular weight heparin could not be better to prevent perioperative myocardial infarction.2 The ratio of peak value of anti-Xa activity which have reached the value of effective anticoagulant activity (0.5-1.0IU/ml) is small in low-dose low molecular weight heparin group. So we propose to increase the dose. The ratio of that is more than 90% in high-dose low molecular weight heparin group. Anticoagulant effect is better.3 11.90% of peak value of anti-Xa activity reach 1.00 IU/ml in high-dose low molecular weight heparin group, which increases the risk of postoperative bleeding, pericardial tamponade and secondary thoracotomy.4 Thoracic duct extubation time is not significantly delayed in high-dose low molecular weight heparin group, so the infection probability caused by drainage tube will not increase.5 Because of the correlation of anti-Xa activity and ACT, we could monitor the low molecular weight heparin using ACT in the coronary artery bypass grafting.
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