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Low Molecular Weight Heparin On Coagulation And Fibrinolysis System Of Patients With Acute Coronary Syndrome: Clinical Study Of Its Effects, Avalability

Posted on:2008-05-27Degree:MasterType:Thesis
Country:ChinaCandidate:W G HouFull Text:PDF
GTID:2144360215489193Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
ObjectivesTo determine plasma level trends of TAFI, PAI-1, PC,Ⅹa,Ⅱa and PAGmax before and after give different low molecular weight heparin(LMWH)(ratio of anti-thrombin and anti-factor X is different to each other.)at two different dosage based on their body weight in patients with acute coronary syndromes, further to investigate LMWH's effects on coagulation system, fibrinolysis system and platelet activation, evaluate LMWH's clinical availability and safety, in order to offer new approaches of anticoagulation and antiplatelet treatment in ACS patients.MethodsWith routine treatments, 82 patients suffered ACS consisting of 26 with NSTEMI and 56 with UAP, ratio of male to female 53:29, aged 45~75 yrs(60.25±15.18yrs), were openly, simply and randomly divided into two groups, which received dalteparin and fraxiparin treatment, respectively. During 7 day's period of treatment, inject subcutaneously dalteparin 5000IU or fraxiparin 4100IU per 12hrs for those body weight less than 65kg; inject subcutaneously dalteparin 7500IU or fraxiparin 6150IU per 12hrs for those body weight more than 65kg. Phlebotomize in elbow veins and determine blood plasma levels of TAFI, PAI-1, PC,Ⅹa,Ⅱa and PAGmax before treatment and 7 days after treatment, while performe the same tests in 30 healthy outpatients as the normal controlled group, which included 18 males and 12 females, aged 48~75yrs(61.45±12.36 yrs), went to hospital for regular checkups during the study period. Input all data into computers and calculate means and standard differences to perform t-test or paired t-test. In the follow-up period, observe rates of endpoint events, including death, recurred myocardial infarction, or unstable angina pectoris, multiple endpoints, massive and minor hemorrhage, in all treatment groups' patients in the 7 days(acute period), 1 month and 6 months after treatment. Statistically analyses were performed withχ~2-test and exact probability method to evaluate different molecular weight LMWH's clinical availability and safety in ACS patients.Results(1)All the plasma TAFI, PAI-1,Ⅹa,Ⅱa and PAGmax levels in ACS patients increased significantly more than those in normal controlled group(P<0.01), while the plasma PC level decreased significantly more(P<0.01); after being devided into NSTEMI and UAP sub-group, the above indecies showed the similar trends when compared with those in normal controlled group(P<0.01). Between NSTEMI and UAP group, there were no significantly differences in PAI-1 and PC levels, but other indecies in the former group increased more significantly than those in the latter group(P<0.01). (2)In the both heparin treatment group, plasmaⅩa,Ⅱa activity and PAGmax level were all decreased more significantly 7 days after treatment than those before treatment(P<0.01), plasma TAFI and PC concentration both increased more significantly than those before treatment(P<0.01). Plasma PAI-1 concentration did not change(NOTE, OR changed wihout statistically significance) (P>0.05) in dalteparin group but increased in fraxiparin group(P<0.01); (3)Before treatment, the above indices showed no significant difference between dalteparin group and fraxiparin group(P>0.05). After treatment, plasmaⅩa andⅡa activity and PAGmax level in the dalteparin group decreased more significantly(P<0.01) and plasma PC concentration increased more significantly(P<0.01) than those in the fraxiparin group, respctively. Plasma TAFI and PAI-1 levels showed no significant difference (P>0.05); (4) For the main availability end points(death, MI, UAP and combined endpoints) and the main safety end points(massive and minor hemorrhage)in 7 days(acute period), 1 month and 6 month after treatment, there were no significant difference when being compared with each other between dalteparin group and fraxiparin group(P>0.05).Conclusion1) There were disturbance of anticoagulatory and fibrinolysis system in ACS patients, in the way of increasement of plasma TAFI and PAI-1 levels,Ⅹa andⅡa activity and ADP-induced PAGmax, decreasement of plasma PC concentration. This alteration was more significant in NSTEMI patients, which suggested that pro-fibrinosis treatment was more important for the group of patients besides anti-coagulatory and anti-platelet approaches.2) Both LMWH showed better anti-coagulatory effects in the two treatment dosage levels decided by body weight[average treatment dosage in dalteparin group(100IU/kg) was higher than that in fraxiparin group(81IU/kg)], which alleviated FactorⅩa andⅡa activity, decreased ADP-induced PAGmax levels, and increased PC level; however, TAFI levels in the two groups increased than those before treatment and PAI-1 level was slightly higher in dalteparin group than that in fraxiparin group, which seemed like relating with heparin dosages and suggested that the treatment dosage levels decided by IU/kg was better than by body weight. PAI-1 levels increased more significantly in the fraxiparin group with no significant difference between two groups, which suggested that there was a strength trend of internal fibrinosis prohibition during LMWH treatment period so that it was important to reinforce pro-fibrinosis treatment at the same time. Because different unit dosage levels of two kinds of LMWH, it was still uncertain which one was better in the anti-platetet clotting.3) Observational clinical endpoints indicated that there was no difference in avaliablity and safety between two LMWH treatment group.
Keywords/Search Tags:Factor Xa, Factor IIa, Acute coronary syndromes, Thrombin Activatable, Fibrinolysis Inhibitor, Plasminogen Activator Inhibitor-1, Protein C, Platelet aggregation
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