| Background:Acute myocardial infarction (AMI), usually caused by intracoronary thrombosis or coronary spasm which was based on unstable atherosclerotic plaque, is the leading cause of death for the general population. The reperfusion therapies with primary percutaneously coronary intervention (PPCI) and intracoronary thrombolysis therapy have significantly reduced the death rate of AMI. However, the mortality in the patients of AMI complicated cardiac shock are still very high which is generally at 50%-60%. Intra-aortic balloon pump (IABP) is one of the most important supporting system to improve the hemodynamic situations of the patients with AMI complicated cardiac shock. However, many complications such as bleeding, lower limb ischemia or embolism, balloon rapture, infection and so forth may happen during the procedure of IABP. However, thrombopenia is the most common and also mortal complication. The average incidence of thrombopenia is about 40% in the patients with IABP procedure and most of them will die if thrombopenia exacerbated further to result in bleeding and/or embolism. However, the mechanism of thrombopenia is not clearly clarified yet even though several investigations proposed a probable relation between thrombopenia and anticoagulation with heparin which was not supported by evidence of laboratory as well as clinical. Therefore, it is clinically very important to investigate the mechanism of thrombopenia. This study was designed to contributed on this topic by comparing the impacts of different anticoagulation on thrombopenia.Objective:Comparing the impacts of low molecular weight heparin and bivalirudin on the dynamic changes of blood platelet counts as well as the level of antibody of platelet factor 4 heparin-dependent antibodies (H-PF4 IgG) during IABP therapy.Methods:This pilot study was designed to totally enroll 60 patients of AMI complicated cardiac shock who underwent PPCI and IABP procedure (during or after PPCI). The patients were randomized into heparin group (n=30) and bivalirudin group (n=30). Enoxaparin or bivalirudin were respectively used as anticoagulation drugs in the heparin group and the bivalirudin group during IABP therapy after PPCI. Intravenous blood samples were collected at different time, including before IABP procedure, at 2 hours, every 24 hours after IABP implantation and until 72 hours after IABP withdrawn, to measure platelets related indices (platelets count, average wide and volume of platelet), red blood cell related indices (red blood cell count, hemoglobin quantitative, hemotocrit), hemolysis related indices (total bilirubin and unconjugated bilirubin) and antibody of H-PF4 IgG Bone marrow smear to discover the proliferation status if patients signed informed consent to undergo bone marrow puncture after IABP withdrawn. Thrombopenia was defined as platelets count below 100×109/L and divided into following three degrees, mild means platelet count between 60-99×109/L, moderate,30～59×109/L and severe, below 30×109/L. GUSTO criteria was used to define bleeding as followings:severe or mortal bleeding means intracranial hemorrhage or unstable hemodynamic changes induced by bleeding, moderate bleeding, blood transfusion was necessary but no unstable hemodynamic changes, mild bleeding, other bleedings.A SPSS 13.0 software system was used for statistical analyzing. A P value< 0.05 was defined as significant statistically difference. For quantitative data, Student t-test was employed for comparing between two groups when ANOVA test for the results of multiple groups. Enumeration data were expressed as percentage and chi-squared test was used to compare the results of groups.Results1. General dataEleven patients were excluded from the statistical analysis due to a short course of IABP therapy (shorter than 24 hours) while the other 49 patients (24 in heparin group and 25 in bivalirudin group) were included in the analysis. The average IABP courses were not significantly different between the heparin group and the bivalirudin group [(4.45±1.50) day versus (4.40±1.47) day, t=0.137, P=0.891]. All of the quantitative data were accord with normal distribution. The average age [(64.8±11.7) years versus (62.2±12.3) years, t=0.753, P=0.455], weight [(61.6±8.3)kg versus (59.8±9.0)kg, t=0.722, P=0.474] were not remarkable different between the two groups. The ratio of male was significant higher in the bivalirudin group than in the heparin group (96% versus 66.7%, Chi-squared value=7.027, P <0.01). There were no statistical differences between the two groups in the ratio of smoking (58.3% versus 72%, P>0.05), Hypertension (47.8% versus 36%, P>0.05), diabetes (25% versus 32%, P>0.05). Before implantation of IABP, the average heart rate [(96±20) bpm versus (100±18) bpm], systolic pressure [(107±26) mmHg versus (109±29) mmHg] and diastolic pressure [(64±15) mmHg versus (67±18) mmHg], there were no statistical differences between the two groups (all of P>0.05). No significant difference was found in the mean diameters of the aortic balloons between the two groups [(36.91±3.61) cm versus (38.24±3.33) cm, t=1.339, P=0.187].2. Platelet, red blood cell and hemolysis related indices2.1 There were no significant differences between the two groups in platelet related indices (platelet count, average wide and volume of platelet), red blood cell related indices (red blood cell count, hemoglobin quantitative, hemotocrit), hemolysis related indices (total bilirubin and unconjugated bilirubin) before implantation of IABP (all P>0.05).2.2 The general tendency of platelet changes in the two groups showed that the count went down rapidly after implantation of IABP and then went slightly up slowly until the withdrawn of IABP. Once withdrawing IABP, platelet count rose rapidly and even surpassed the baseline level. The decrease of platelet number was remarkably smaller in bivalirudin group than in heparin group (t=4.149, P=0.043), but there were no significant differences between the two groups when comparing at the same time points (all P>0.05).The average volume and wide of platelets in the two groups appeared to increase and reached the peak at 72 hours after implantation of IABP, then tended to decrease slightly and finally maintained at a higher level than the baseline at 72 hours after withdrawn of IABP. There were no any statistical differences between the two groups (all P> 0.05).2.3 The number of red blood cells, hemoglobin quantitative and hemotocrit decreased rapidly and persisted on the potency until the withdrawn of IABP, and then increase slightly but not got back to the levels of baseline even at 72 hours after the withdrawn of IABP. The amplitude of changes were greater in the heparin group than in bivalirudin group (P<0.05). However, there were no any statistical differences between the two groups when comparing at the same time points (all P>0.05)2.4 The basic level of total bilirubin and unconjugated bilirubin were not significant different between the two groups (P>0.05). However, the level of total bilirubin and unconjugated bilirubin significantly increased after implantation of IABP, which were much higher in the heparin group than in the bivalirudin group (P <0.05). There were no any statistical differences between the two groups when comparing at the same time points (all P>0.05).3. The changes of antibody to H-PF4 IgGBefore implantation of IABP, there was no significant difference between the two groups in the level of antibody to H-PF4 IgG [(10.50±4.89) ng/ml versus (10.70±4.60) ng/ml, t=0.149, P=0.883]. However, the level of antibody to H-PF4 IgG was much higher in the heparin group than in bivalirudin group [(46.79±27.02) ng/ml versus (32.08±19.41) ng/ml, t=2.089, P=0.043]. The increase amplitude of antibody to H-PF4 IgG was greater in the heparin group (36.27±26.92 ng/ml) than in the bivalirudin group (21.61±20.97 ng/ml, t=2.031, P=0.048).4. Thrombopenia and bleedingThrombopenia was developed in 8 patients in the heparin group, which was consisted of 7 mild and 1 moderate, when 5 mild thrombopenia was developed in the bivalirudin group. There was no statistical difference of the incidences between the two groups (33% versus 20%, P=0.291). Three patients with moderate bleeding and 2 with mild bleeding in the heparin group when 1 moderate and 1 mild in the bivalirudin group. There was no significant difference of the bleeding rate between the groups (P=0.823).5. The founding of bone marrow smearSeven patients,3 from the heparin group and 4 from bivalirudin group, signed the informed consent to undergo bone marrow puncture after IABP was withdrawn. Bone marrow smear showed that in all of the patients, whoever with or without thrombopenia, bone marrow was in the status of vivid proliferation.Conclusions1. Platelets number went down rapidly after implantation of IABP and got to the lowest level at the 3rd day, then regained slowly and got back or even surpassed to the baseline after the withdrawn of IABP.2. Mechanical rupture of platelets was the major mechanism of thrombopenia during IABP therapy when heparin-induced-thrombopenia also played an very important role in it.3. Compared with low molecular weight heparin, bivalirudin showed a potential to reduce the incidence of thrombopenia while used as a anticoagulation during IABP therapy. |
PDF Full Text Request