Von Willebrand factor-glycoprotein Ⅰb axis and ischemic stroke / 国际脑血管病杂志

Due to the narrow time window of traditional reperfusion therapy and the presence of the risk of reperfusion injury, it is of great significance to study the pathogenesis of ischemic stroke and explore methods to reduce reperfusion injury from the perspective of pathophysiology. This article expounds the functions of von Willebrand factor (vWF) and platelet glycoprotein (GP) Ⅰb and their roles in hemostasis, thrombosis, and inflammation. It is believed that pharmacological blockade of the interaction of vWF-GP Ⅰb may contribute to the treatment of ischemic stroke. In addition, its clinical significance in ischemic stroke and ischemic brain injury was further discussed.

Trombastenia de Glanzmann: conceptos clave de la enfermedad / Glanzmann thrombasthenia: key concepts of the disease

La trombastenia de Glanzmann (TG), es un trastorno autosómico recesivo en el cual hay una reducción grave o ausencia de la agregación plaquetaria. Se debe a las alteraciones cualitativas o cuantitativas de la integrina α IIb o de integrina β 3, codificados por los genes ITGA2B e ITGB3 y relacionadas con la glicoproteína IIb/IIIa, que intervienen en la activación plaquetaria. La mayor incidencia de TG ha sido reportada en la población judía-iraquí, pero también se ha presentado en Israel, Jordania, Arabia saudita, Italia y, en menor número, en familias gitanas y pakistaníes. A pesar de ser poco frecuente, este trastorno se debe sospechar en casos de trastornos hemorrágicos graves espontáneos o inducidos por traumatismos, que varían desde hemorragias gastrointestinales y mucocutáneas, como epistaxis y hemorragias gingivales recurrentes de difícil manejo, las cuales son potencialmente mortales y en más del 75 por ciento de los casos requieren transfusión sanguínea o plaquetaria. Para realizar la confirmación del diagnóstico, los hallazgos de laboratorio se caracterizan por tiempos de sangrado prolongados, retracción del coágulo disminuida y respuestas anormales de agregación plaquetaria a estímulos fisiológicos. Aunque, actualmente no existe una cura para la enfermedad, el tratamiento adecuado con transfusiones plaquetarias y en caso de refractariedad, el uso del factor VIIa, permiten un buen pronóstico para los pacientes. Aún queda mucho por estudiar en estos casos debido a esto se están realizando nuevos estudios para la posibilidad de otros tratamientos, entre ellos la terapia génica plaquetaria(AU)

Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder in which there is a severe reduction or absence of platelet aggregation. It is due to the qualitative or quantitative alterations of integrin #945; IIb or integrin #946; 3, encoded by the ITGA2B and ITGB3 genes and related to glycoprotein IIb / IIIa, which intervene in platelet activation. The highest incidence of GT has been reported in the Jewish-Iraqi population, but it has also been reported in Israel, Jordan, Saudi Arabia, Italy, and in smaller numbers in Gypsy and Pakistani families. Despite being uncommon, this disorder should be suspected in cases of severe spontaneous or trauma-induced bleeding disorders, ranging from gastrointestinal and mucocutaneous hemorrhages such as epistaxis and recurrent, difficult to manage gingival hemorrhages, which are potentially fatal and more than 75 percent of cases require blood or platelet transfusion. To confirm the diagnosis, the laboratory findings are characterized by prolonged bleeding times, decreased clot retraction and abnormal platelet aggregation responses to physiological stimuli. Although there is currently no cure for the disease, adequate treatments with platelet transfusions and in case of refractoriness, the use of factor VIIa, allow a good prognosis for patients. There is still much to study in these cases, because of this, new studies are being conducted for the possibility of other treatments, including platelet gene therapy(AU)

Safety and effectiveness of combination application of thrombus aspiration and intracoronary injection of tirofiban / 重庆医学

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.

In-Lab Upfront Use of Tirofiban May Reduce the Occurrence of No-Reflow During Primary Percutaneous Coronary Intervention. A Pilot Randomized Study / Uso de Tirofibana em Laboratório pode Reduzir Ocorrência de não Reperfusão Durante Intervenção Coronariana Percutânea Primária. Um Estudo Piloto Randomizado

Abstract Background: Despite successful opening of culprit coronary artery, myocardial reperfusion does not always follows primary percutaneous coronary intervention (PPCI). Glycoprotein IIb/IIIa inhibitors are used in the treatment of no-reflow (NR), but their role to prevent it is unproven. Objective: To evaluate the effect of in-lab administration of tirofiban on the incidence of NR in ST-elevation myocardial infarction (STEMI) treated with PPCI. Methods: STEMI patients treated with PPCI were randomized (24 tirofiban and 34 placebo) in this double-blinded study to assess the impact of intravenous tirofiban on the incidence of NR after PPCI according to angiographic and electrocardiographic methods. End-points of the study were: TIMI-epicardial flow grade; myocardial blush grade (MBG); resolution of ST-elevation < 70% (RST < 70%) at 90min and 24h after PPCI. Results: Baseline anthropometric, clinical and angiographic characteristics were balanced between the groups. The occurrence of TIMI flow < 3 was not significantly different between the tirofiban (25%) and placebo (35.3%) groups. MBG ≤ 2 did not occur in the tirofiban group, and was seen in 11.7% of patients in the placebo group (p=0.13). RST < 70% occurred in 41.6% x 55.8% (p=0.42) at 90min and in 29% x 55.9% (p=0.06) at 24h in tirofiban and placebo groups, respectively. Severe NR (RST ≤ 30%) was detected in 0% x 26.5% (p=0.01) at 90 min, and in 4.2% x 23.5% (p=0.06) at 24h in tirofiban and placebo groups, respectively. Conclusion: This pilot study showed a trend toward reduction of NR associated with in-lab upfront use of tirofiban in STEMI patients treated with PPCI and paves the way for a full-scale study testing this hypothesis.

Resumo Fundamento: Mesmo com abertura da artéria coronária culpada bem sucedida, a reperfusão miocárdica nem sempre sucede a intervenção coronariana percutânea primária (ICPP). Inibidores da glicoproteína IIb/IIIa são usados no tratamento do fenômeno de não reperfusão (NR), mas seu papel para preveni-lo não está comprovado. Objetivo: Avaliar o efeito da administração, em laboratório, de tirofibana sobre a incidência de NR em infarto agudo do miocárdio com supra do segmento ST (IAMCSST) tratado com ICPP. Métodos: Pacientes com IAMCSST tratados com ICPP foram randomizados (24 tirofibana e 34 placebo) neste estudo duplo-cego para avaliar o impacto de tirofibana intravenosa sobre a incidência de NR após ICPP de acordo com métodos angiográficos e eletrocardiográfico. Os desfechos do estudo foram: fluxo epicárdico TIMI (grau), grau de fluxo miocárdico (MBG), resolução da elevação do segmento ST < 70% (RST < 70%) aos 90 minutos e 24 horas após ICPP. Resultados: Características antropométricas, clínicas e angiográficas basais eram equilibradas entre os grupos. A ocorrência de fluxo TIMI < 3 não foi significativamente diferente entre os grupos tirofibana (25%) e placebo (35,3%). MBG ≤ 2 não ocorreu no grupo tirofibana, e foi detectado em 11,7% dos pacientes do grupo placebo (p=0,13). RST < 70% ocorreu em 41,6% x 55,8% (p=0.42) aos 90 minutos, e em 29% x 55,9% (p=0,06) em 24 horas nos grupos tirofibana e placebo, respectivamente. NR grave (RST ≤ 30%) ocorreu em 0% x 26,5% (p=0,01) aos 90 minutos, e em 4,2% x 23,5% (p=0,06) em 24 horas nos grupos tirofibana e placebo, respectivamente. Conclusão: Este estudo piloto mostrou uma tendência de redução de NR associada ao uso, em laboratório, de tirofibana em pacientes com IAMCSST tratados com ICPP, e abre caminho para um estudo em escala real que teste essa hipótese.

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome / Mutações gênicas das glicoproteínas plaquetárias e resposta ao tirofiban na síndrome coronariana aguda

CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.

RESUMO CONTEXTO E OBJETIVOS: Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP). MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T ), Ib (Thr/Met ), IIb (Ile/Ser ) e IIIa (PIA ) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da glicoproteína IIIa antes da administração de tirofiban do genótipo selvagem (41% ± 22% versus 56% ± 21%; P = 0,035). Genótipos mutantes da glicoproteína IIIa correlacionaram-se moderadamente com menor inibição plaquetária (r = -0,31; P = 0,030). Após a administração tirofiban, as mutações das glicoproteínas Ia, Ib, IIb, e IIIa não influenciaram o grau de inibição da agregação plaquetária e mortalidade intra-hospitalar. CONCLUSÕES: Mutações das glicoproteínas Ia, Ib, IIb e IIIa não influenciaram a agregação plaquetária em resposta ao tirofiban nos pacientes com angina instável e IAMSSST.

Pathogenesis and prenatal diagnosis of hereditary Glanzmann thrombasthenia / 临床儿科杂志

Objective To explore the gene sequencing and prenatal diagnosis of Glanzmann thrombasthenia (GT). Methods The blood samples were drawn from one case of phenotype GT pediatric patient, patient’s parents, and one normal control. The amniotic lfuid and cord blood from the fetus of patient’s mother were collected. When the fetus was born 2 days, the blood was drawn. The coagulation routine test and platelet aggregation test were performed. The expression of platelet membrane glycoprotein (GP) IIb and GPIIIa were tested by lfow cytometry. Microsatellite technology is used to determine whether fetal cord blood is contaminated with maternal cells. The expressed region and the junctional zone between exon and introns of GPIIb and GPIIIa were ampliifed by PCR technology from blood sample of patient, patient’s parents, and fetus’s cord and 2 days after birth. The PCR products were then subjected to DNA sequencing. Results Adenosine diphosphate (ADP) cannot induce the platelet aggregation in the patient. The max rate of the platelet aggregation in the fetus’s cord blood was half of the normal. However, the max aggregation rate induced by ADP in the blood sample of parents and fetus 2 days after birth were equal to normal. The mean lfuorescence intensity (MnX) of platelet membrane GPIIb and GPIIIa in the patient were 10%and nearly zero of the normal control, respectively, while those in the parents, the fetus’s cord blood and 2 days after birth were more than 90%and 30%to 50%of the normal control. The cast-off cells in amniotic lfuid and the DNA in cord blood analysis by microsatellite technology conifrmed that the amniotic lfuid and cord blood not contaminated by maternal cells. Gene analysis showed the heterozygosis mutation in exon6 A3829→C and exon9 G42186→A of the patient’s GPIIIa led to the amino acid heterozygosis mutation in GPIIIaHis281→Tyr and Cys400→Pro. These two mutations came from the father and the mother separately. However, there was only one heterozygosis mutation in exon9 G42186→A in the cast-off cells in amniotic lfuid, the fetus’s cord and blood 2 days after birth. Conclusion This GT patient have double heterozygosis mutation. The fetus has heterozygosis mutation conifrmed after birth.

Clinical effect of super-selective intracoronary administration on acute myocardial infarction patients / 中华老年医学杂志

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.

Research progress of application of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syn-drome / 心血管康复医学杂志

Through occupying binding site of glycoprotein IIb/IIIa receptor,platelet glycoprotein IIb/IIIa inhibitor (GPI)inhibit the combination of fibrinogen and the receptor,then inhibit platelet aggregation.GPI is the most powerful anti-platelet drug and possesses application value in ACS now.This article made an overview on the newest research progress of safety and effectiveness of GPI in ACS.

Application of tirofiban in ischemic stoke thrombolysis and endovascular therapy / 国际脑血管病杂志

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.

Safety and Efficacy Comparison of Platelet Glycoprotein IIb/IIIa Antagonist in Treating STEMI Patients by Intracoronary-intravenous Administration and Intravenous Administration:A Meta-analysis / 中国循环杂志

Objective: To compare the safety and efifcacy of platelet glycoprotein IIb/IIIa antagonist in treating STEMI patients by intracoronary-intravenous administration and intravenous administration. Methods: We searched PubMed, Embase, Cochrane library, CNKI, VIPH and Wanfang database, the retrieval stopped at 2014-03. According to 5.0.2 Cochrane handbook, 2 scientists collected 2494 STEMI patients treated by IIb/IIIa antagonist from 20 references, and they were divided into 2 groups. Combination group, the patients received intracoronary, then intravenous administration, n=1258 and Intravenous group, the patients receive only intravenous administration, n=1236. RevMan 5.0 software was used for Meta-analysis. Results: At 1 month after PCI treatment, compared with Intravenous group, the Combination group had better conditions of TIMI 3, TMP 3, ST segment recovery, MACE occurrence and MI area changes, all P0.05. Conclusion: Intracoronary-intravenous administration of platelet glycoprotein IIb/IIIa antagonist had the better effect for treating STEMI patients without increasing the side effects of post-operative bleeding and thrombocytopenia.

Correlation between platelet membrane glycoprotein Ⅱb HPA-3 polymorphism and ischemic stroke in Chinese Han population / 国际脑血管病杂志

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.

Investigation of platelet membrane glycoprotein Ibα gene polymorphisms in children with Kawasaki disease / 中华实用儿科临床杂志

Objective To investigate the association between platelet glycoprotein Ibα (GPIbα) gene HPA-2a/b polymorphisms and the risk of Kawasaki disease (KD) and that complicated with coronary artery lesion (CAL).Methods A total of 30 patients with KD and 60 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism and agarose gel electrophoresis for the HPA-2a/b polymorphism in GPIbα gene.Results For HPA-2a/b polymorphism in GPIbα gene,there was only genotype TC and CC of HPA-2a/b polymorphism in GPIbα gene in children with KD and healthy controls,and genotype TF was not found in both groups.There were no significant differences between KD patients and the controls in genotype frequencies of CC,TC and TT and allele frequencies of C and T (x2 =0.052,0.048,all P ＞ 0.05) ; also there was no significant difference between KD patients with CAL and that without CAL in genotype and allele frequencies (x2 =2.672,2.481,all P ＞ 0.05).Conclusion No association is found between HPA-2a/b polymorphism in GPIbα gene and the risk of KD or its complication of CAL in this study.

Research advances in monitoring platelet function in patients with coronary artery disease / 中华检验医学杂志

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.

Effect of combined anti-platelets drugs on platelet activation in the elderly patients with acute coronary syndrome / 中华老年医学杂志

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.

Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid.

Platelets aggregation around migrating tumor cells offers protection against the cytotoxic activity of the natural killers cells (NKC). The ascorbic acid in 3X10-3Μ concentration completely inhibited platelet aggregation, decreased thromboxane B2 levels, and inhibited the expression of platelet membranic receptor GpIIb/IIIa in non stimulated platelets, and increased the NKC cytotoxicity in an average rate of 105, 61, and 285% in the NKC/targets cells ratios 12.5:1, 25:1 and 50:1 respectively. The results suggest the role of ascorbic acid in increasing the susceptibility of tumor cells to NKC; the ascorbic acid could be used as part of a multidrug therapy to treat diseases which up to now have been treated only through chemotherapy.

Clinical efficacy and safety of the combination of an intracoronary tirofiban infusion plus percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction / 中华老年医学杂志

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.

Acute Cerebral Infarction Following Intravenous Glycoprotein IIb/IIIa Inhibitor for Acute Myocardial Infarction

Stroke is a rare but serious complication of acute myocardial infarction (AMI). Currently, glycoprotein (GP) IIb/IIIa inhibitor is used in clinical practice for acute coronary syndromes and percutaneous coronary interventions (PCIs). The incidence of stroke in patients receiving GP IIb/IIIa inhibitor during PCIs is very low. We report the case of a 47-year-old man who presented with AMI and suffered an acute cerebral infarction after infusion of a GP IIb/IIIa inhibitor following primary PCI.

Tirofiban in percutaneous coronary intervention of patients with acute non-ST segment elevation myocardial infarct: Safety and efficacy / 第二军医大学学报

Objective: To evaluate the efficacy and safety of tirofiban, a platelet glycoprotein IIb/ IIIa Inhibitor, in percutaneous coronary intervention (PCI) of patients with acute non-ST segment elevation myocardial infarct (NSTEMI). Methods: A total of 114 patients with acute NSTEMI were enrolled in the trial from Sep. 2005 to Jan. 2007; they were randomly divided into 2 groups: tirofiban group (n=57) and placebo group (n=57). Patients in tirofiban group were given tirofiban for 24 h after PCI. All patients were routinely given heparin, aspirin and clopidogrel before CPI. The composite occurrence of death, myocardial infarction (MI), need for target vessel revascularization (TVR) after PCI, and the adverse effects (hemorrhage and thrombocypenia) were compared between the 2 groups. Results: One (1.8%) patient had angina pectoris and the other (1.8%) developed subacute thrombus in control group within 24 h after PCI; there was no such event in the tirofiban group. Two (3.6%) patients developed angina pectoris and 2 (3.6%) developed subacute thrombus within 30 days after PCI in control group; one patient (1.8%) in birofiban group developed angina pectoris and one patient in birofiban group developed subacute thrombus. Each group had one case (1.8%) of upper digestive tract bleeding during hospitalization. No intracranial hemorrhage, skin/mucosa hemorrhage, thrombocytopenia, or death occurred in the 2 groups. Intravenous tirofiban treatment reduced the composite occurrence of death of NSTEMI patients after PCI (P<0.05). There was no significant difference in occurrence of complications such as intracranial hemorrhage, skin/mucosa hemorrhage, or thrombocytopenia between the 2 groups. Conclusion: Intravenous tirofiban treatment after PCI can reduce the composite occurrence of death, MI, and need for TVR without increasing the adverse reactions of the drugs; it is safe and effective in patients undergoing early coronary stenting.

EDTA Inhibits the Binding of Clone 96.2C1, an Anti-CD41a Monoclonal Antibody, to the Platelets and Addition of Heparin and CaCl2 to the Antibody Neutralizes the EDTA-induced Inhibitory Effect / 대한혈액학회지

BACKGROUND: The binding of some monoclonal antibodies platelet glycoprotein (GP) IIb/IIIa, which is frequently used for flow cytometric immnophenotyping, is known to be inhibited by EDTA. To select the ideal antibodies to be included in the 'Acute Leukemia Panel' for immunophenotyping of acute leukemia, we compared the inhibitory effect of EDTA on the binding of 5 different clones of monoclonal antibodies to platelet GP IIb/IIIa. We also discovered a simple method to neutralize this inhibitory effect. METHODS: Flow cytometric measurement of the number of platelet GP IIb/IIIa binding sites with different anticoagulants was performed using a panel of 5 clones of monoclonal antibodies against CD41 (clone PM6/248), CD41a (clone 96.2C1 & clone HIP8), CD41b (clone HIP2) and CD61 (clone VI-PL2), and the results are expressed as the mean equivalent soluble fluorochrome (MESF) values. RESULTS: The MESF value of the EDTA platelets stained with anti-CD41a, clone 96.2C1 antibody showed a significantly lower value than the MESF of platelets anticoagulated with heparin or citrate (P<0.001). The inhibitory effect of EDTA on the binding of anti-CD41a, clone 96.2C1 antibody to the platelets was neutralized by addition of heparin and CaCl2. The mean MESF value of EDTA platelets stained with anti-CD41a, clone 96.2C1 antibody was significantly increased by the addition of heparin and CaCl2 (P=0.0001). CONCLUSION: The false-negative results of the binding of anti-CD41a, clone 96.2C1 antibody to the platelets seem to be due to the calcium chelating property of EDTA, and the addition of CaCl2 and heparin could be used as an easy compensatory measure for the inhibitory effect of EDTA on other antibodies as well.

Significance of specific autoantibodies against platelet glycoprotein in Idiopathic thrombocytopenic purpura / 中国综合临床

Objecfive To detect the specific autoantibodies against platelet in idiopathic thrombocytopenic purpura (ITP) and to study the relationship between these autoantibodies and the severity of ITP as well as therapeutic effect.Methods Autoantibodies (GPⅡbⅢa and GPIb) against platelet glycoprotein was measured by a monoclonal antibody immobilization of platelet antigen assay (MAIPA) in 40 ITP patients.Results 10 patients had mono-specific antibodies to GP Ⅱ bⅢa and 6 patients had mono-specific antibodies to GPIbα.Another 20 patients had antibodies to both antigens and 4 patients had no detectable antibody to either platelet antigen.There Was negative correlation between the antibody against GPⅡbⅢa(b=-0.071,P<0.01),CPIbα(b=0.092,P<0.01) and platelet counts.The ratio of refractory cases in patients with antibodies to both antigens(8/20) was significantly higher than that in patients with mono-specific antibodies(1/16)(χ2=6.09,P<0.05).Conclusion The specific autoantibadies against platelet might be valuable for discrininafion of idiopathic thrombocytopenic purpura and non immune thrombocytopenia.The types of antibodies are related with severity of ITP and therapeutic effect.