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【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.
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【Objective】 To evaluate the effect of adding platelet GPⅡb/Ⅲa receptor inhibitor (A adjuvant) into the Batroxobin cup (A cup) on the accuracy of the thromboelastogram (TEG) platelet aggregation function test using the functional fibrinogen (function fiber cup) test results as a standard. 【Methods】 From December 2019 to May 2020, 100 (persons) whole blood samples were collected from patients who visited the Department of Neurology, Department of Cardiology, Department of General Affairs and Department of Rehabilitation of our hospital for TEG platelet aggregation function test, and the blood standard samples were divided into MA <25 mm group (n=50) and MA≥25 mm group (n=50) according to the A-cup blood clot intensity (MA) value (mm) measured by TEG, the two groups were subdivided into A cup group (n=50, respectively), A auxiliary group (adding A auxiliary in A cup) (n=50, respectively), and functional fiber cup group (n=50, respectively), each subgroup was tested once again. The linear correlation, platelet inhibition and the consistency of drug efficacy interpretation results in platelet Adenosine diphosphate (ADP) and Arachidonic acid (AA) pathway respectively between the three subgroups were compared. 【Results】 (1) In the MA<25mm group, the inhibition rates of ADP and AA pathway in platelet of A cup, A adjuvant and functional fibrin cup subgroups were (32.00±17.44) % vs (30.19±17.44) % vs (30.07±16.18) %, (24.3±33.53) % vs (22.53±30.9) % vs (22.37±31.2) %, respectively (R2 were all>0.975); (2) In the MA≥25 mm group, the inhibition rates of ADP and AA pathway in platelet of A cup, A adjuvant and functional fibrin cup subgroups were (34.34±33.59) % vs (18.45±24.42) % vs (18.01±24.33) %, (23.19±39.33) % vs (8.48±21.75) % vs (8.31±21.7) % ( R2 between the A cup group and the A adjuvant group were all<0.8, and R2 between the A adjuvant group and the functional fibrinogen cup group were all >0.975); (3)Take the test result of the functional fibrinogen cup as the standard, the correct rates of ADP and AA pathway drug efficacy interpretation were 82% (41/50) vs 100% (50/50) and 84% (42/50) vs 100% (50/50) respectively (P<0.05) between the A-cup group and the A adjuvant group, while the interpretation results of drug efficacy of the two pathway were consistent between the A adjuvant group and the functional fibrin cup group (P>0.05). 【Conclusion】 Adding A adjuvant to TEG platelet aggregation function test can effectively inhibit non-specifically activated platelets in the A cup in the detection of platelet aggregation function, truly reflect the function of fibrinogen and improve the accuracy of platelet inhibition rate.
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Objective To investigate the interventional therapy effect of combination application of thrombus aspiration and intracoronary injection of tirofiban for treating heavy thrombosis burden of infarction related vessel in the patients with acute anterior myocardial infarction.Methods The patients with acute anterior myocardial infarction undergone direct primary percutaneous coronary intervention in the hospital were retrospectively analyzed.The group A received simple thrombus aspiration during transcutaneous PCI and the group B received the combination treatment of thrombus aspiration and intracoronary injection of tirofiban in direct PCI.Results The patients with myocardial perfusion grade less than 3 during thrombolysis during myocardial infarction(TIMI) in the group B were significantly less than those in the group A(P＜0.05).The cardiac magnetic resonance imaging(MRI) results indicated that the area of myocardial infarction in the group B was smaller than that in the group A(P＜0.05).The color echocardiography results showed that the left ventricular diastolic volume(LVDV) and left ventricular ejection fraction(LVEF) in the group B were significantly better than those in the group A(P＜0.05).Conclnsion The combination application of thrombus aspiration and intracoronary injection of tirofiban is safe and effective in direct PCI.
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Objective To investigate the effect of super-selective intracoronary administration on acute myocardial in farction patients.Methods A total of 240 patients with ST-segment elevation myocardial infarction who received emergency percutaneous coronary intervention in our department from March 2012 to January 2014 were selected and divided into the intravenous drug administration group (n=77),the conventional intracoronary drug administration group (n=81) and the super-selective intracoronary drug administration group (n=82).Parameters,including the Thrombolysis in Myocardial Infarction (TIMI) classification,ST segment resolution after operation,peak values of creatine kinase MB (CK-MB) and troponin-I (cTn-I),left ventricular ejection fraction,left ventricular end-diastolic diameter (LVEDD),major adverse cardiovascular events and bleeding events,were compared between the groups.Results There were no significant differences in TIMI flow grade between the three groups (x2 =0.14,P=0.529).The percentage of patients with complete ST segment resolution after operation was higher in the super-selective intracoronary drug administration group than in the intravenous drug administration and conventional intracoronary drug administration groups (74.4％ vs.62.3％,61.7％,x2 =8.24,P＜0.05).Peak values of CK-MB and cTn-I were lower in the super-selective intracoronary drug administration group than in the other groups (P＜0.05).There were no significant differences in left ventricular ejection fraction and LVEDD between the three groups after operation,but left ventricular ejection fraction and the incidence of angina pectoris significantly improved in the super-selective intracoronary drug administration group than in the other groups after a three month follow-up (P＜0.05).There were no significant differences in target lesion revascularization,nonfatal myocardial infarction and druginduced thrombocytopenia between the three groups (P ＞ 0.05).Conclusions Super-selective intracoronary drug administration can significantly enhance cardiac function and alleviate angina pectoris in patients with acute myocardial infarction,and should be a recommended method.
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Tirofiban,a platelet glycoprotein (GP) Ⅱ b/Ⅲ a receptor antagonist has been widely used in the treatment of acute coronary syndrome (ACS) and percutaneous transluminal coronary intervention.This article introduces the mechanism of action of tirofiban and its application in intravenous thrombolysis,intraarterial thrombolysis,and endovascular therapy in ischemic stroke,emphasizing the safety and effectiveness of tirofiban in the application of the emergency cerebral angioplasty.
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Objective To investigate the distribution of glycoprotein (GP) Ⅱ b HPA-3 polymorphism in Chinese Han population in Tianjin and its correlation with ischemic stroke.Methods The patients in this study were divided into either a ischemic stroke group (n =150) or a control group (n =135).Genotyping was conducted by using polymerase chain reaction-restriction fragment length polymorphism and was verified by sampling sequencing Each genotype and allele frequency distribution and its correlation with ischemic stroke were compared.Results The ab genotype,bb genotype and b allele frequency in the patient group were significantly higher than those in the control group (P =0.000),while aa genotype and a allele frequency were significantly lower than those in the control group (P =0.000).There were no significant differences in the frequencies of GPⅡ b genotype and b allele between the different gender and the age groups in the patient group.Although there were no significant differences in genotype frequencies between all etiologic subtypes,b allele frequency in the large artery atherosclerotic stroke subgroup was significantly higher than that in the small vascular occlusive stroke subgroup and that in the cardioembolism subgroup (61.8％ vs.46.7％ vs.47.5％ ;x2 =6.573,P =0.037).Multivariate logistic regression analysis showed that hypertension (odds ratio [OR] 7.475,95％ confidence interval [CI]3.700-15.003; P =0.000) and b allele (OR 3.678,95％ CI 1.245-10.863; P =0.018) were the independent risk factors for ischemic stroke.Conclusions GP Ⅱ b HPA-3 polymorphism may be associated with the risk of ischemic stroke onset.Carrying b allele may be an independent risk factor for ischemic stroke,especially large artery atherosclerotic stroke.
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Antiplatelet therapy and stent implantation have been the dominant treatment to reduce the mortality of patients with coronary artery disease.Recently,studies have showed that adverse cardiac events still occur in part of patients with coronary artery disease after the antiplatelet treatment with aspirin and/or clopidogrel.Thus,resistance to aspirin and clopidogrel has attracted increasing attention.It will be great benefit to these patients who were identified resistance and made tailoring antiplatelet therapy So far many platelet function tests has been used in clinical to monitor the reaction of the antiplatelet drugs for prevention and treatment of thrombosis in patients with coronary artery disease.These monitoring tests may be chosen based on different antiplatelet drugs including aspirin,clopidogrel and GP Ⅱ b/Ⅲ a antagonist.The results of antiplatelet drug resistance may be different due to different platelet function methods,thus the related clinical adverse events needs further verification.
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Objective To investigate the effect of combined anti-platelets drugs on platelet activation in the elderly patients with acute coronary syndrome (ACS).Methods Totally 72 elderly patients with ACS were divided randomly into two groups according to age ≤ 80 years and ＞ 80 years.Aspirin 100 mg/d plus clopidogrel 75 mg/d were used in all the patients for 2 weeks.The positive glycoprotein Ⅱb/Ⅲa and P-selectin expressions on the surface of platelets were assessed with flow cytometry (FCM) after the platelets were activated by adenosine diphosphate (ADP) and arachidonic acid.Results The expressions of GP Ⅱb/Ⅲa and P-selectin were (73.5± 11.0,71.2±8.7) ％ at baseline and (51.3±9.1,57.3±12.4)％ after anti-platelets medicine more than 14 days in group of age≤80 years.than 14 days.The expression of GP Ⅱb/Ⅲa and P-selectin were (78.3 ±12.7,75.8±8.6)％ on the surface of platelet at baseline in group of age＞ 80 years,after anti-platelets medicine treatment were (41.2±8.5,47.3±10.3)％.The positive expressions of GP Ⅱb/Ⅲa and P-selectin in group of age＞ 80 years were decreased compared with those in group of age≤ 80 years after combination of medicines treatment (P＜0.05).Conclusions Combined aspirin and Clopidogrel treatment have a more strong effect in inhibiting the activation of platelets in the elderly patients more than 80-year with ACS.
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Objective To assess the clinical efficacy and safety of the combination of intracoronary tirofiban infusion(ICTI) plus percutaneous coronary intervention(PCI) in patients with acute ST-elevation myocardial infarction (STEAMI). Methods The 128 cases with STEAMI were enrolled in this study. They were randomly divided into trial group and control group. The 10 μg/kg tirofiban were infused into the infarct related artery (IRA) within 5 minutes through the cather after coronary angiography in trial group (n=64). Normal saline in matched dose was infused into IRA after coronary angiography in control group (n=64). The coronary thrombosis and revascularization status were assessed within 10 minutes after injection. Postoperative bleeding complications were observed in all cases. Adverse cardiovascular events and cardiac function were followed up within 1 month in all cases. Results There were 33 cases whose thrombus burden was reduced within 10 minutes after the infusion of tirofiban in trial group, including 26 cases of thrombolysis in myocardial infarction (TIMI) ≥1. There were 6 cases whose thrombus burden was reduced within 10 minutes after the infusion of normal saline in control group, including 3 cases TIMI ≥ 1. The coronary thrombosis and revascularization status were better in trial group rather than in control group (P＜0.01). Adverse cardiovascular events occurred in 5 cases within 1 month, including 2 cases in trial group and 3 cases in control group (P＞0.05). New York heart association functional class and ejection fraction values were better in trial group rather than in control group within 1 month (P＜0.05). Postoperative bleeding complications occurred in 14 cases by TIMI criteria , including severe and mild bleeding in 2 cases in trial group and 1 cases in control group (P＞0.05), but no significant bleeding occurred in 8 cases in trial group and in 3 cases in control group (P＜0.01). Conclusions The combination of intracoronary infusion of tirofiban plus PCI is effective and safe for thrombolysis and revascularization in IRA in patients with STEAMI.
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Batifiban,a synthetic cyclic peptide,is a potent platelet glycoprotein GPⅡb/Ⅲa an-tagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects,and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55,110,or 220 μg/kg,or multiple doses of an bolus followed intravenous infusion for 24 h (180 μg/kg of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma lev-els of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner,consistent with its mechanism as a GP Ⅱb/Ⅲa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
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Objective To investigate the effect of tirofiban on myocardial necrosis biomarker after percutaneous coronary interventions(PCI)in patients with aspirin resistance(AR).Methods 374 consecutive patients with aspirin 100 mg≥1 week,receiving no other antiplatelet therapy,scheduled for PCI were enrolled.all patients were given an loading dose of 300 mg clopidogrel at least 12 hours before PCI and an 75 mg maintenance dose per day.Patients were randomized into tirofiban group(n=38)and control group(n=45)after PCI.The levels of CKMB,TnI at 8,12,and 24 hours after PCI were measured in all patients;if the CK-MB,TnI value was above normal upper limitation,it was considered elevated.Results 83 patients were AR(22.2%)and 54.2%of them are females.The frequencies of CK-MB elevation were 15(39.5%)in tirofiban group and 19(42.2%)in control group,and TnI elevation was 18(47.4%)and 23(51.1%)in the two groups respectively.Conclusion Tirofiban can not decrease the elevation level of CK-MB and TnI in patients with AR after PCI.
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Objective To study the GPⅡb/Ⅲa gene mutations of eight glanzmann thrombasthenia(GT) pedigrees. Methods Responses of eight probands to different agonists were observed by platelet aggregation test and the amount of αⅡb and β3 was determined by flow cytometry. All the exons of Ⅱb and Ⅲ a genes were amplified by PCR followed by sequencing for mutational screening. Further analysis of the normal population excluded the possibility of mutational sites as a polymorphism. Results Eight probands showed normal PLT counts, dispersion of the platelet particles without aggregation, prolonged bleeding time and severely reduced platelet aggregation in response to the physiological agonists- ADP, epinephrine, and collagen, but relatively normal aggregation of PLT in response to ristocetin. Flow cytometry showed that all probande were Ⅰ type GT, except that proband 2 was Ⅲ type GT and proband 6 was Ⅱ type GT. The sequencing results showed that twelve different types mutations were present in eight probands, including GIOA, Gl412T, GII99A, 1525deiC, G2223T, C2671T, 2930delG, IVSI5 (-1) delG, A2334C, C1750T, 69-79del and CA70A. We were not able to detected any mutations in GP Ⅱb/Ⅲa gone on proband 3. Conclusions GT is mainly caused by GPⅡb/Ⅲa gene mutations. G10A, 69-79del, C470A,G1412T, G2223T, C2671T and 1525delC were the novel mutations causing GT.
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Objective To evaluate the effect of homemade tirofiban in percutaneous coronary intervention for acute myocardial infarction. Methods Sixty four cases of consecutive acute myocardial infarction were enrolled and divided into two groups: the tirofiban group (n=34) and the control group (n=30). In addition to intravenous heparin, patients in the tirofiban group received a bolus dose of tirofiban (10 ?g/kg) before stenting and followed by a 0.15 ?g/(kg?min) infusion for up to 12-36 hours. The control group only receive routine intravenous heparin therapy before and during PCI. The post operation TIMI blood flow, bleeding events and major adverse cardiac events were observed in the 2 groups. Results A 97.1% of patients in the tirofiban group compared with 76.7% in the control group obtained TIMI grade 2-3 flow respectively. Among them, 91.2% in the tirofiban group but 70.0% in the control obtained TIMI 3 flow. There were no serious in-hospital bleeding complications and MACE. Conclusion Homemade tirofiban is effective in improving the TIMI grade and prognosis of acute myocardial infarction after PCI.
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Objective To quantitate platelet GPIIb/IIIa occupancy and to evaluate the performance of the method, and investigate GPIIb/IIIa occupancy for the patients with leukemia.Methods GPIIb/IIIa occupancy was quantified by flow cytometry (FCM) and the method was evaluated according to guidelines published by NCCLS and ICSH; meanwhile,GPIIb/IIIa occupancy for 13 healthy donors and 16 patients with acute leukemia was investigated.Results The results demonstrated coefficients of variation (CV) for within-batch, between-batch and overall imprecision were
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Objective To investigate changes of platelet activation in the elderly patients with obstructive sleep apnea-hypopnea syndrome(OSAHS)before and after the application of nasal continuous positive airway pressure(nCPAP). Methods Ninety patients diagnosed as OSAHS by polysomnography(PSG)were selected as trial group,30 non-OSAHS by PSG were as control group, and 16 severe OSAHS patients were treated by nCPAP and taken as nCPAP therapy group. GMP-140 and GPⅡb/Ⅲa were measured by ELISA and compared in these groups. Results Plasma levels of GMP-140 and GPⅡb/Ⅲa of patients with moderate and severe OSAHS were (16.6?2.3)?g/L vs (18.9?3.1)?g/L, and 38 468?952/ 49 673?1037 vs 39 867?1264/50 899?2476 respectively; and those of control group were (14.8?2.1) ?g/L, 37 672?769/ 48 469?1672 respectively.Plasma levels of GMP-140 and GPⅡb/Ⅲa were significantly higher in patients with moderate to severe OSAHS than those in control group(P
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Aim To investigate the inhibitory effect of atrase B on human platelet aggregation induced by activated complement.Methods By employing CVF to activate complement,the effect of atrase B on gel filtered platelet aggregation induced by activated complement was measured by turbidimetry and the expression of P-selectin and GPⅡb/Ⅲa on platelet membrane were detected by flow cytometry.Results Atrase B inhibited platelet aggregation and the expression of P-selectin and GPⅡb/Ⅲa on platelet membrane induced by activated complement.Conclusion Anticomplementary protein atrase B from Naja atra venom can significantly inhibit platelet activation and aggregation induced by activated complement.
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0 5).Conclusions The measurement of platelet membrane GPⅡbⅢa complexes by FCM can provide a simple, sensitive and reliable method for G T diagnosis,and also can be applied to analysis of GT family pedigree.
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Objective To investigate the function and clinical significance of platelet-derived microparticles (PMP), glycoprotein(GP)Ⅱb-Ⅲa, PagT and blood-lipid in whole blood of patients with cerebro-thrombotic diseases before and after treatment. Methods The quantity of PMPs, activation ratio of GPⅡb-Ⅲa and PAgT were measured before and after treatment of cerebro-thrombotic patients by using flow cytometry and platelet adhesion instrument. Blood-lipid concentration was measured by automatic-biochemical analyzer. Results PMP, GPⅡb-Ⅲa , PAgT, TC, TG, and LDL were (223?54)/10 4 Plt, (77.98?14.22)%, (69.78?16.93) %, (5.12?0.85) mmol/L, (1.78?0.28) mmol/L, and (3.49?0.66) mmol/L respectively before treatment; and were (136?18)10 4Plt, (40.71?11.64) %, (58.12?12.51)%, (4.84?0.73) mmol/L, (1.43?0.33) mmol/L, and (3.03?0.62) mmol/L,respectively in the treatment group. These parameters were significantly decreased than that before treatment (P
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Objective To investigate the effects of gelatins and dextran on fibrinogen and platelet glycoproteinⅡb/Ⅲa (GPⅡb/Ⅲa).Methods One hundred and five patients for selective cholecystectomy were randomly divided into four groups. In groupⅠ normal saline 30ml/kg was infused, in groupⅡ dextran-70 30ml/kg,in groupⅢ urea-linked gelatin 30ml/kg and group Ⅳ modified fluid gelatin 30ml/kg. The blood samples were taken before infusion ,two hours and three hours after the infusion, to measure platelet maximum aggregation rate (MAR), levels of Fbg and GPⅡb/Ⅲa,respectively.Results As compared with those in other groups, MAR and level of GPⅡb/Ⅲa decreased significantly in groupⅡ(P
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Obejective To assess the influence of apheresis and wash on platelet function and morphology.Methods To determine the count,size,distribution,agglutination,aggregation,GMP 140 & GPⅡb/Ⅲa of the platelet from the peripheral blood prior to apheresis and aphersed or washed platelets produced by CS 3000 plus.Results Both apheresed and washed platelets showed decreased PDW,PCT & MPV,but there were no statistical difference between groups.There were no difference in platelet adhesion,aggregation,CD 62p +,CD 41a +,and CD 62p +expression.Both apheresed and washed platelets showed increased CD 41a + expression,but there was no difference between apheresed and washed platelets.Conclusion Flow cytometry measurement of GMP 140 & GPⅡb/Ⅲa may be used for in vitro platelet function assessment.Although apherisis can induce mild platelet activation,platelets apheresed or washed by CS 3000 plus have reliable quality and can be used in a variety of clinical conditions.