The Clinical Value Of Thromboelastography In The Anti-platelet Therapy And Clinical Efficacy And Safety Of Butylphthalide In Patients With Acute Cerebral Infarction

Part1 Clinical Study of Using Thrombelastography to Detect Coagulation Function and Platelet Function in Patients with Acute Cerebral InfarctionBackground and objective With the change of people's lifestyles and the aging of population structure,the incidence of cerebrovascular disease(CVD)is increasing rapidly,which has serious adverse effects on people's physical and mental health,as well as social and economic development.In general,CVDs contains a series of brain disease caused by brain damage,which can be divided into cerebral hemorrhagic disease and ischemic diseases.Among them,the ischemic cerebrovascular disease is the most common,and arterial thrombosis with atherosclerosis as the most common pathogeny is the main subtype..At present,the carotid arteries and intracranial arteries are used to screen arterial plaques,and evaluate the nature,size and location of the plaques.In addition,a variety of factors can led to platelet activation,and because of the adhesion and aggregation function of the platelet,caused a high risk of the formation of arterial thrombosis.How to detect platelet function is a neglected item in clinical work.A large number of previously reports showed that in the therapy of cardiovascular disease,using platelet function testing results to adjust and guide the anti-platelet aggregation drug regimen revealed an important positive clinical significance.There are several methods for platelet function testing,such as turbidimetric method,resistance method,and so on.The defects of traditional method include the test results maybe affected by blood component damage and hyperlipidemia,and the electrode must be cleaned after detection,it is hard to meet the needs of clinical work.At present,thrombelastography(TEG)is commonly used as an indicator of platelet function,especially for platelet aggregation function in clinic.In this study,TEG was used to evaluate the coagulation function and platelet function in patients with acute cerebral infarction.The routine coagulation test,platelet function and the nerve function defect were employed in the patients with acute cerebral infarction and the correlation between TEG parameters and the above indexes,to further investigate the application value of TEG for guiding clinical treatment and intervention measures in patients with acute cerebral infarction.Methods In this study,88 patients with acute cerebral infarction treated in our hospital from January 2016 to December 2016 and 30 patients who underwent physical examination in our hospital during the same period were selected as the subjects.Among them,the acute cerebral infarction patients were divided into mild group,moderate group and severe group according to the National Institute of Health stroke scale(NIHSS).6 ml fasting venous blood were collected after admission and before treatment,including 2 m L for TEG detection,2 m L for blood coagulation analysis and 2 m L for routine blood testing.The TEG parameters including K value,R value,MA value and CI value,blood coagulation index(including PT,APTT,FIB,DD)and platelet parameters(including platelet count,mean platelet volume,platelet volume distribution width,plateletcrit)were collected.The differences between the different groups in the parameters of TEG parameters,coagulation function and platelet function were compared,and the correlation between TEG parameters and coagulation function and platelet function parameters was analyzed by Pearson correlation analysis.Results 1.88 patients with acute cerebral infarction,included 56 males and 32 females,aged 43-82 years,mean(59.6±9.2)years old,62 with hypertension and 36 with diabetes mellitus.30 cases of physical examination,included 18 males and 12 females,aged 45-83 years,mean(60.3±8.9)ears.According to the NIHSS,the severity of acute cerebral infarction was 21 cases in mild group,37 cases in moderate group and 30 cases in severe group.2.The analysis results TEG parameters showed that R value and K value in patients with acute cerebral infarction was less than that in the healthy subjects,and the alpha angle and MA value was greater than that in the healthy controls,the differences were statistically significant(P < 0.05),the CI value had no significant difference(P > 0.05),and with the aggravation of the condition,R and K values showed a decreasing trend and the alpha angle and MA value showed an increasing trend,the differences were statistically significant(P < 0.05).The analysis results of blood coagulation function showed that DD and FIB in patients with acute cerebral infarction were significantly higher than that in healthy controls,the differences were statistically significant(P < 0.05),PT and APTT had no significant difference(P > 0.05).With the aggravation of the condition,DD and FIB values increased and show the increasing trend,the difference there was statistically significant(P < 0.05),PT and APTT had no significant differences(P > 0.05).The analysis results of platelet parameters showed that the mean platelet volume,platelet volume distribution width and thrombocytocrit in patients with acute cerebral infarction were significantly higher than those in healthy controls,the differences were statistically significant(P < 0.05).With the aggravation of the condition,mean platelet volume,platelet volume distribution width,platelet hematocrit increased showed the increasing tendency,the differences were statistically significant(P < 0.05),there was no significant difference between the platelet counts(P > 0.05).3.The results of Pearson correlation analysis between the TEG parameters and blood coagulation function indexes showed that R value and K value was positively correlated with PT and APTT,negatively correlated with DD and FIB(P<0.05);While the a angle,MA value,CI was negatively correlated with PT and APTT,positively correlated with DD and FIB(P<0.05).The results of Pearson correlation analysis between the TEG parameters and platelet function parameters showed that R value was negatively correlated with mean platelet volume,the correlation coefficients was-0.255(P<0.05),MA value was positively correlated with plateletcrit,the correlation coefficients was 0.254(P<0.05).There was no statistical significant correlation between TEG and the other indicators of platelet function(P > 0.05).Conclusions TEG by graphically dynamic process of coagulation monitoring,detection is simple and rapid,intuitive,sensitive,accurate and timely reflect the blood coagulation state,have a certain diagnostic value for cerebrovascular disease,can help the clinicians to early predict the pathogenesis prognosis and severity,and to provide the relevant clues to guide the clinical treatment,and may further guide the individualized treatment.Part2 Application of Thromboelastography in The anti-platelet Therapy in Patients with Acute Cerebral InfarctionPurpose: To explore the application value of Thrombelastography(TEG)to evaluate the effect of anti-platelet therapy with aspirin or aspirin plus clopidogrel in patients with acute cerebral infarction,so as to guide the individualized adjustment of drug treatment on platelet aggregation in patients with acute cerebral infarction.Method: In this study,88 patients with acute cerebral infarction treated in our hospital from January 2016 to December 2016 were selected as the subjects and were divided into mild group,moderate group and severe group according to NIHSS.After admission,the patients were divided into two groups according to the random number table: dual therapy with aspirin and clopidogrel(dual therapy group)and single anti-platelet drug group(single therapy group).Among them,the single therapy group was given oral aspirin 100mg/d,medication for 5 days,the arachidonic acid(AA)was used as inducer to detected the maximum aggregation rate of platelet within 5mins to obtain the platelet inhibition rate.The aspirin resistance patients were transferred to oral clopidogrel 75 mg/d for 5 days,the adenosine diphosphate(ADP)was used as inducer to detect the maximum aggregation rate of platelet within 5mins to obtain the platelet inhibition rate.The dual therapy group received oral aspirin,100mg/d+ clopidogrel,75 mg/d,and for 5 days the AA pathway and ADP pathway were used to obtain the platelet inhibition rate.Result: 1.45 cases in the dual therapy group,including 29 males and 16 females,aged 43-82 years,mean(61.4±10.5)years old,35 cases with hypertension,17 cases with diabetes.According to the NIHSS,the severity of acute cerebral infarction was mild in 11 cases,moderate in 18 cases,and severe in 16 cases.43 patients in single therapy group,including 27 males and 16 females,aged 45-81 years,mean(58.1±11.8)years old.27 patients with hypertension and 19 with diabetes mellitus.According to the NIHSS,the severity of acute cerebral infarction was mild in 10 cases,moderate in 19 cases,and severe in 14 cases.There was no significant difference between the two groups in sex constitution,age,concomitant disease and the distribution of the severity of the disease(P > 0.05).2.The inhibition rate of platelet aggregation aspirin produced by AA pathway(AA%)was(79.5±21.7)%,the inhibition rate of platelet aggregation clopidogrel produced by ADP receptor pathway inhibition rate(ADP%)was(55.9±19.4)%,the difference was statistically significant(t=3.72,P < 0.05).3.In the dual therapy group,aspirin effect good(29 cases,accounting for 64.4%)while clopidogrel effect poor(low reaction + invalid,11 cases,accounting for 24.4%)was more than clopidogrel effect good(14 cases,31.1%)while aspirin effect poor(low reaction effect + invalid,1 cases,accounting for 2.22%),the difference was statistically significant(c2=13.221,P=0.000),suggesting that inhibitory effect of aspirin on platelet aggregation was better than clopidogrel.4.After treatment for 5 days,the differences of the TEG parameters between the two groups were not statistically significant(P > 0.05).The results suggested that there was no significant difference in the coagulation state between the dual therapy group and single therapy group.5.Of the 43 patients treated with aspirin,27 had normal anti-platelet aggregation,and 16 had aspirin resistance(low or ineffective).For patients with a normal response to aspirin,TEG parameters change before and after treatment were statistically significant(P < 0.05),embodied in the R and K values increased significantly,alpha angle and MA value decreased significantly,suggesting that patients with high blood coagulation state has been improved.The inhibition rate of platelet aggregation was 76.27%.The results showed that the aggregation function of platelets was well inhibited.6.Sixteen patients with aspirin resistance were transferred to oral clopidogrel 75mg/d for after 5 days,TEG detection results showed that there was 14 patients whose inhibition of platelet aggregation was improved significantly,the average inhibition rate increased to(59.83±8.27)%,the difference was statistically significant(P < 0.05).Conclusion: 1.It has high clinical value for using TEG test to evaluate the efficacy of anti-platelet therapy in patients with acute cerebral infarction.2.In the dual anti-platelet therapy,aspirin has a stronger inhibitory effect on platelet aggregation in patients with acute cerebral infarction than that of clopidogrel.3.The response to aspirin or clopidogrel treatment was different.Some patients with low or ineffective response to clopidogrel probably have good effective response to aspirin.4.The effect of dual therapy with aspirin and clopidogrel or single aspirin therapy on blood coagulation function has no significant difference.Part 3 Clinical Efficacy and Safety of Butylphthalide in the Treatment of Actue Cerebral InfarctionPurpose: To investigate the clinical efficacy and safety of butylphthalide combined with conventional dual anti-platelet therapy(aspirin + clopidogrel)in patients with acute cerebral infarction.Methods: In this study,90 patients with acute cerebral infarction treated in our hospital from January 2016 to December 2016 were selected as the subjects and were divided into two groups according to the random number table: dual anti-platelet therapy with aspirin and clopidogrel(control group)and aspirin + clopidogrel + Butylphthalide and Sodium Chloride Injection group(observation group).All patients were given routine treatment for patients with ischemic stroke,including brain protection therapy,lowering the blood lipid,blood glucose control,blood pressure control,continuously improve the cerebral micro-circulation,expanding blood volume,symptomatic treatment for patients with other underlying diseases.On this basis,the control group were treated with oral Aspirin Enteric-coated Tablets(100mg/d)+ Clopidogrel Bisulfate Tablets(first days for the first time the dose of 300 mg,from the second day of the 75 mg/d).On the basis of the control group therapy scheme,combined with Butylphthalide and Sodium Chloride Injection(intravenous drip,25mg/time,twice daily,a single infusion duration more than 50 min,interval at least 6 hours).The course of treatment was 2 weeks.The NIHSS and Barthel index(BI)were used to evaluate the improvement of neurological function and life ability before and after treatment,TEG detection was used to evaluate the improvement of blood coagulation state before and after treatment,serum neuron specific enolase(NSE)was used as an indicator for brain neuron injury,serum interleukin-6(IL-6),C reactive protein(CRP)and homocysteine(Hcy)were used an indicators for stress factors level.And through the blood and urine routine,electrocardiogram,liver and kidney function examination,necessary review skull CT,observation of adverse reactions such as the presence of bleeding events,clinical treatment safety was evaluated.Results: 1.45 cases in the control group,including 29 males and 16 females,aged 43-82 years,mean(61.4±10.5)years old,35 cases with hypertension,17 cases with diabetes.11 cases of patients with multiple cerebral infarction,14 cases of basal ganglia in patients with cerebral infarction,20 patients with lacunar infarction.According to the NIHSS,the severity of acute cerebral infarction was mild in 11 cases,moderate in 18 cases,and severe in 16 cases.45 patients in the observation group,including 28 males and 17 females,aged 49-77 years,mean(57.9±9.8)years old.27 patients with hypertension and 19 with diabetes mellitus.12 cases of patients with multiple cerebral infarction,15 cases of basal ganglia in patients with cerebral infarction,18 patients with lacunar infarction.According to the NIHSS,the severity of acute cerebral infarction was mild in 10 cases,moderate in 21 cases,and severe in 14 cases.There was no significant difference between the two groups in sex constitution,age,concomitant disease,type of infarction and the distribution of the severity of the disease(P > 0.05).2.Before treatment,there was no significant difference in the NIHSS score,BI score and serum NSE,IL-6,CRP,Hcy levels between the two groups(P > 0.05).After treatment,NIHSS scores and serum NSE,IL-6,CRP,Hcy levels were significantly decreased,BI score increased significantly(P<0.05).3.After treatment,the R and K values of the observation group were significantly higher than that of the control group,and the MA value,alpha angle and CI value were significantly lower than those in the control group,the difference was statistically significant(P < 0.05).The high blood coagulation degree of the observation group is lower than that of the control group.4.After treatment,the NIHSS scores and serum NSE,IL-6,CRP,Hcy levels in the observation group were significantly lower than that of the control group,BI score was significantly higher than that of the control group,the differences were statistically significant(P <0.05).The results showed that the recovery effect of neurons and neurological impairment,improvement of living ability and the stress condition in the observation group were better than those in the control group.5.The total effective rate of observation group was 88.9%(40/45),which was significant higher than that of the control group[68.9%(31/45)],the difference was statistically significant(c2=3.104,P=0.002).6.During the treatment period,two groups of patients were not observed obvious adverse reactions.In the observation group there were 2 cases of mild elevation of glutamic pyruvic transaminase,4 cases of gastrointestinal reaction,1 cases of rash.In control group,3 cases of mild rise of urea nitrogen,4 cases of gastrointestinal reaction and 1 cases of rash.Routine blood test and electrocardiogram examination showed no abnormal change.It is suggested that the addition of butylphthalide is safe on the basis of conventional dual anti-platelet therapy.Conclusions: Based on the conventional dual anti-platelet therapy scheme,combined with butylphthalide in the treatment of acute cerebral infarction,the clinical curative effect was definitive.It was helpful to correct the disorder of blood coagulation function and lower the body's stress,thereby enhance the recovery of neurological function,improve the living ability of patients and the drug was safety.It was worthy of further clinical research and application.