Effect of Qingkailing injection on platelets function preserved in vitro / 中国输血杂志

【Objective】 To investigate the effect of Qingkailing injection on platelet function preserved in vitro. 【Methods】 A total of 15 bags of plateletpheresis (≥250 mL/bag), adding Qingkailing injection(1.25 mL/bag) at the final concentration of 1%, were stored at 22 ℃ with gentle agitation as the experimental group, and samples were collected on day 1, 3, 5, 8, 10 and 14 to detect the thromboelastogram (TEG), CD62p expression rate and mitochondrial membrane potential (JC-1). The control group was set up synchronously, with the same volume and storage conditions as the experimental groups, and samples were taken on day 1, 3 and 5 after preservation to undertake the same test items as the experimental groups. The differences of detection indexes between the two groups were compared. 【Results】 1) In the experimental group, there was no significant change in K and α during day 1 to 14(P>0.05). The R value (min) increased from 6.12±1.58 to 11.02±2.26, and the CI value changed from 0.27±1.24 to -10.47±3.51 (P0.05), but decreased to 53.18±2.71 on day 8 and 22.88±3.45 on day 14 (P0.05), but JC-1 (%) was 86.75±3.88 vs 70.36±19.8 on day 5 (P<0.05). In the experimental group, JC-1(%) was 81.04±9.50 vs 71.38±8.77 vs 82.77±7.17 on day 8, 10 and 14, respectively. 【Conclusion】 The activation and aggregation as well as anti-apoptosis function of plateletpheresis, adding Qingkailing injection at the final concentration of 1%, are similar to those of routine preservation.

Establishment and identification of a human megakaryocytic cell line with low Ley expression / 中国输血杂志

【Objective】 To establish a stable human megakaryocytic cell line with low expression of Ley antigen to further study the role of Ley on activation of platelets. 【Methods】 The expression level of the Ley antigen in a human megakaryocytic cell line, DAMI, was determined using Western Blot and flow cytometry. The expression level of genes that encode fucosyltransferase (FUTs), which was involved in the biosynthesis of Ley antigen, was also determined to identify the candidate genes to be knocked out. The candidate FUT gene was knocked out via a CRISPR/Cas 9 gene knockout system and cells with low Ley antigen expression were sorted by flow cytometry. The sorted cell line was cultured and characterized. 【Results】 The Ley was expressed intensively on DAMI cell. FUT1 and FUT4 mRNA was expressed relatively higher, both may be key enzymes for the biosynthesis of the Ley antigen. In the DAMI cell line with the knockout of FUT1 gene, the expression of the Ley adntigen was remarkedly reduced, while cell proliferation was not affected compared to the wildtype control cells. 【Conclusions】 Since various FUTs contributes to the biosynthesis of the Ley antigen, the knockout of the primary one of them cannot totally block its biosynthesis, but only reduce its expression. In this study, a stable FUT gene knockout human megakaryocyticcell line is established using CRISPR/Cas 9 technology, which provides basis for the study of the impact of the Ley antigen on platelet functions.

Activation, function and metabolismofapheresis platelets during storage / 中国输血杂志

【Objective】 To analyze the changes of activation, function and metabolism of apheresis platelets during storage. 【Methods】 Five groups of apheresis platelets(n=10per group), stored up to 5 days at 20~24℃ with agitation, were sampledat day0(4 hours within collection), 1, 2, 3 and 4, respectively to assess the activation indexes as PAC-1 and CD62P and platelet function was evaluated by thromboelastogram.The platelet counts and related parameters were determined, and the biochemical indexes such as pH, glucose, lactic acid and lactate dehydrogenase reflecting metabolism were measured and statistically analyzed. 【Results】 The CD62P (%) and PAC-1 (%) of apheresis platelets with different storage duration showed significant differences(P0.05). Significant differences were notable in platelet biochemical indexesby groups using variance analysis(P<0.05). The pH value and glucose were the lowest in platelets with 4-day storage, while lactic acid and lactate dehydrogenase were the highest. 【Conclusion】 The storagelesion of apheresis platelets occurs as the activation, function and metabolism of platelets developed as the storage prolonged.

Platelet function tests and Chinese medicines with antiplatelet function:a review / 中国中药杂志

Platelet function tests have been increasingly used to assist in the diagnosis of platelet disorders and prethrombotic state, monitoring of the efficacy of antiplatelet therapies, and personalized treatment. On the basis of light transmission aggregometry, new methods for platelet function test have been developed successively. At present, the research and development of platelet function detector is in its infancy in China. The active constituents of antiplatelet Chinese medicines can be classified into terpenoids, flavonoids, saponins, organic acids, lignans, diketones, volatile oils, and stilbenes. The results of dose-antiplatelet effect relationship of Chinese medicines and the active constituents showed that the effective concentration of the extracts or monomers of Chinese medicines was at micromolar level(μmol·L~(-1)), among which salvianolic acid B and ginkgolide K, ginkgolide B, and ginkgolide A had the strongest antiplatelet effect. These results suggest that the antiplatelet effect of Chinese medicine may be weaker than that of chemical drugs and biological products. Therefore, it is necessary to explore the structure-activity relationship of the active constituents in existing Chinese medicines and further improve their efficacy through structure modification. The antiplatelet effect of Chinese medicines and the constituents involves multiple pathways and multiple targets. These research results provide a reference for clinical application of them. However, there is still a lack of large-scale multi-center clinical trials to confirm the efficacy and safety of them. The regularity of the relationship between the structures of various constituents and their corresponding functions is still unknown and the relevant signal transduction pathways and structure-activity relationship need to be further studied. This paper summarized and analyzed the determination methods of platelet functions and the research results of antiplatelet Chinese medicines, which is of reference value for the research of effective and safe antiplatelet Chinese medicines.

Respuesta de los sujetos con hipertensión arterial a los fármacos antiagregantes plaquetarios / Response of hypertensive subjects to antiplatelet drugs

Introducción: La terapia con antiagregantes plaquetarios es recomendada como prevención secundaria de eventos cardiovasculares en personas con hipertensión arterial. Sin embargo, en la práctica clínica se encuentran personas que no responden al tratamiento y presentan recurrencia de eventos vasculares. Objetivo: Evaluar la respuesta de los sujetos hipertensos a los fármacos antiagregantes plaquetarios. Material y Métodos: Estudio transversal, observacional descriptivo y comparativo, con 299 sujetos con hipertensión arterial esencial y 96 no hipertensos (como control), que estaban consumiendo antiagregantes plaquetarios. Los sujetos hipertensos fueron agrupados de acuerdo con el consumo de fármacos antihipertensivos. Se les determinó su agregación plaquetaria al colágeno en plasma, rico en plaquetas, según el Método de Born. La respuesta a la terapia antiplaquetaria se clasificó en cuatro categorías (óptima, moderada, pobre y no respuesta) de acuerdo con la agregación plaquetaria. Resultados: Se observó una ligera mejor respuesta a los antiagregantes plaquetarios, aunque no estadísticamente significativa, por parte de los hipertensos sin fármacos antihipertensivos (35,7 por ciento óptima y 42,9 por ciento moderada), en relación con los hipertensos que usaban antihipertensivos (32,7 por ciento óptima y 26,5 por ciento moderada) y los no hipertensos (30,2 por ciento óptima y 30,2 por ciento moderada). Además, se encontró que 17,7 por ciento de los sujetos no hipertensos, 14,3 por ciento de los hipertensos sin fármacos antihipertensivos y 13,2 por ciento de los hipertensos con antihipertensivos no estaban respondiendo a los antiagregantes plaquetarios. Conclusiones: La respuesta a los fármacos antiagregantes plaquetarios de los sujetos hipertensos consuman o no fármacos antihipertensivos es heterogénea y similar a la de los sujetos no hipertensos(AU)

ABSTRACT Introduction: Therapy with antiplatelet drugs is recommended as secondary prevention of cardiovascular events in people with arterial hypertension. However, in the clinical practice, there are people who do not respond to treatment and evidence a recurrence of vascular events. Objective: To evaluate the response of hypertensive patients to antiplatelet drugs. Material and Methods: Cross-sectional, observational, descriptive and comparative study that included 299 subjects with arterial hypertension and 96 non-hypertensive subjects (control group) who were taking antiplatelet drugs. The hypertensive subjects were grouped according to the consumption of antihypertensive drugs. Platelet aggregation collagen in platelet-rich plasma was determined using the turbidimetric Born's method. The response to the antiplatelet therapy was classified in four categories (good, moderate, poor and non-responsiveness) in accordance with the platelet aggregation. Results: There was a slightly better response to antiplatelet drugs, although it was not statistically significant in hypertensive subjects without antihypertensive drugs (35,7 percent good and 42,9 percent moderate) in relation to hypertensive subjects who were taking antihypertensive drugs (32,7 percent good and 26,5 percent moderate) and the non-hypertensive ones (30,2 percent good and 30,2 percent moderate).Besides, it was found that 17,7 percent of non-hypertensive subjects and 14,3 percent of the hypertensive ones without antihypertensive drugs and 13,2 percent of hypertensive subjects with antihypertensive drugs were not responding to the treatment with antiplatelet drugs. Conclusions: The response of hypertensive patients to antiplatelet drugs, either taking antihypertensive drugs or not, is heterogeneous and similar to the response of the non-hypertensive subjects(AU)

Platelet Aggregation Pattern on Light Transmission Aggregometry Among Malaysian Healthy Individuals

@#Introduction: Platelet aggregation test using light transmission aggregometry (LTA) is considered as the gold standard for evaluation of platelet function. Variations of platelet aggregation had been reported in apparently healthy individuals whereby a normal cut–off value established locally is highly recommended. This study aims to determine the platelet aggregation pattern and the preliminary findings on reference values for multiple agonists–induced platelet aggregation among Malaysian healthy individuals in a single centre. Method: A total number of 63 informed consented healthy individuals consisted of Malay, Chinese and Indian were recruited among staff and blood donors at National Blood Centre, Kuala Lumpur. Platelet aggregation was measured using LTA against adenosine diphosphate 10 µM (ADP10), collagen 0.19 mg/mL (COL), ristocetin 1.5 mg/mL (RIS), arachidonic acid 1 mM (AA) and epinephrine 10 µM (EPI). Results were expressed as percent final aggregation (%FA). Reference values were calculated from mean±2SD. Results: Age, gender and ethnic groups had no significant effect on platelet aggregation. A variability of platelet aggregation response to EPI was observed among the healthy individuals. Ten of 33 respondents (30%) had impaired aggregation with <20% FA in response to EPI. The local population showed a slightly higher aggregation pattern in response to COL, RIS, AA and EPI (excluding non-responders) compared to manufacturer’s reference values. Conclusion: This study has provided a glimpse of the aggregation pattern of the local nationality showing considerable differences in the reference values from manufacturer’s; thus highlighting the need of establishing local reference values.

The effect of diclofenac on bleeding, platelet function, and consumption of opioids following cardiac surgery

Abstract Objective: To establish whether the use of diclofenac reduces the administration of opioids and how it affects bleeding and platelet function after the coronary artery bypass grafting (CABG) surgery with use of cardiopulmonary bypass (CPB). Methods: A total of 72 patients undergoing CABG surgery were included in this retrospective randomized study and divided into two groups (34 patients received diclofenac and the control group of 38 patients did not). For postoperative analgesia, both groups were prescribed opioids (piritramide). The primary endpoint was to establish the consumption of opioids. The secondary endpoint was to determine bleeding and the function of platelets 20 hours after the surgery. Results: The consumption of piritramide (diclofenac group 26±8 mg vs. control group 28±8 mg), the blood loss, and the function of platelets did not significantly differ between the groups within 20 hours after surgery. C-reactive protein (CRP) was statistically significantly lower in the diclofenac group than in the control group (33±15 mg/L vs. 46±22 mg/L, respectively, P<0.05). Conclusion: The study concluded that patients administered with diclofenac after the heart surgery did not consume less opioid analgesics and did not exhibit less symptoms linked to the consumption of opioids. Diclofenac in clinically administered doses does not interfere with the function of platelets and does not cause increased bleeding. Lower CRP in the diclofenac group may indicate a reduced inflammatory response after CPB. Therefore, diclofenac could be safe for use in patients undergoing CABG surgery but its value in reducing opioid consumption should be questioned.

Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

Temporal Variability of Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor

BACKGROUND AND OBJECTIVES: The degree of antiplatelet response to P2Y12 inhibitors has been associated with clinical outcomes. The aim of this study was to test the variability of platelet reactivity over time among patients treated with clopidogrel or ticagrelor. METHODS: A single-center cohort of acute coronary syndrome patients that underwent percutaneous coronary intervention (PCI) was analyzed. Platelet reactivity was measured at baseline, 48 hours after PCI, 1 month, and 6 months after clopidogrel (n=79) or ticagrelor (n=93) treatment. High on-treatment platelet reactivity (HPR) was defined as ≥47 U, assessed by multiple electrode platelet aggregometry. RESULTS: Platelet reactivity in the clopidogrel group increased over time, 38.2±21.7 U at 48 hours, 41.4±22.3 U at 1 month, and 44.7±25.5 U at 6 months (p=0.018, 48 hours to 6 months). However, platelet reactivity in the ticagrelor group was not significantly changed, 21.4±12.6 U at 48 hours, 20.0±12.2 U at 1 month, and 22.8±13.8 U at 6 months (p=0.392). A platelet reactivity change over time of more than 20U was found in 67.1% of the patients with clopidogrel group and 34.4% of ticagrelor group (p<0.001). Between 48 hours and 6 months, 43% of patients changed their responder status in the clopidogrel group, and 13% in the ticagrelor group (p<0.001). CONCLUSIONS: Although ticagrelor treatment resulted in less temporal variability of platelet reactivity than clopidogrel treatment in terms of HPR, platelet reactivity varied over time in a significant proportion of patients.

Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

Effectiveness of Platelet Function Analyzer-100 for Laboratory Detection of Anti-Platelet Drug-Induced Platelet Dysfunction

BACKGROUND: High on-treatment platelet reactivity (HTPR) is the phenomenon wherein patients exhibit normal platelet activity in laboratory testing despite adequate adherence to anti-platelet treatment. We investigated the detection rates of Platelet Function Analyzer (PFA)-100 (Dade Behring AG, Düdingen, Switzerland) for drug-induced platelet dysfunction and analyzed potential contributors to HTPR with practical PFA-100 data over six years. METHODS: We used data from 6,957 patients who underwent PFA-100 testing after receiving aspirin, clopidogrel, or non-steroidal anti-inflammatory drugs (NSAIDs). Of these, 6,163 patients were tested with only the collagen/epinephrine cartridge (Col/EPI) of PFA-100; 794 were tested with both Col/EPI and the collagen/ADP cartridge (Col/ADP). We calculated PFA-100 closure time (CT) for each drug and compared the clinical and laboratory characteristics of the patients with prolonged CTs and normal CTs (i.e., HTPR). RESULTS: In Col/EPI, 73.2% (365/499), 72.6% (390/537), and 55.3% (3,442/6,228) patients showed prolonged CTs for aspirin, clopidogrel, and NSAIDs, respectively. In Col/ADP, prolonged CTs were observed in 37.4% (34/91), 43.2% (35/81), and 29.6% (200/676) of patients receiving aspirin, clopidogrel, and NSAIDs, respectively. Of the patients tested with both cartridges, 88.9% (48/54), 95.3% (41/43), and 89.0% (577/648) of the patients receiving aspirin, clopidogrel, and NSAIDs had prolonged CTs, and 10.0% (79/794) showed normal CTs regardless of drugs. For clopidogrel users (both cartridges), there were more patients with malignancies in the normal CT than prolonged CT group. CONCLUSIONS: PFA-100 is not sufficiently effective for laboratory screening of drug-induced platelet dysfunction. Malignancy may contribute to clopidogrel-related HTPR in PFA-100.

Platelet function tests: A 5-year audit of platelet function tests done for bleeding disorders in a tertiary care center of a developing country

Introduction: The platelet function disorders remain largely undiagnosed or incompletely diagnosed in developing nations due to lack of availability of tests like lumiaggregometry, granule release assay or molecular testing. We performed a retrospective analysis of all the platelet function test (PFT) carried out in past 5 years by Light transmission aggregometery (LTA) using a panel of agonist. The indications and the test results were analyzed by two hematopathologist with the aim to look into the present diagnostic facilities or lack of it for correct diagnosis. This is essential for better management and genetic counselling. Materials and Methods: The PFT was performed both on patients and healthy unrelated age specific controls by light transmission aggregometry on Chronolog platelet aggregometer using platelet rich plasma. The panel of agonists included ADP (10?m/l and 2.0 ?m/l), epinephrine (10.0 ?m/l), collagen (2?g/ml), arachidonic acid (0.75 mM) and ristocetin (1.25 mg/ml & 0.25 mg/l). Results: The 5 years records of 110 cases were audited, 101 of these were tested for clinical bleeding , 35 adults and 66 children. The adults included 29 women and 6 men, 17 to 82 years of age. The children were 16 years to 3 months of age, 30 girls and 36 boys. Platelet function test abnormality was found in 31.6% (32/101) cases ,a majority remained undiagnosed of these about 21% had clinically significant bleeding.The cases diagnosed included Glanzmann Thromboasthenia-11 , von Willebrand Disease-6, Bernard Soulier'syndrome-1, storage pool disorder-6, mild defect of Epinephrine-3, isolated defect with collagen in1. Conclusion: An epidemiologically large proportion of platelet function disorders amongst people living in developing nations remain undiagnosed. This lacunae needs to be highlighted and addressed on larger scale. The options available are to increase the available armamentarium of tests or international collaboration with a specialized laboratory to aid in complete diagnosis.

Fisiología plaquetaria, agregometría plaquetaria y su utilidad clínica / Platelet physiology, platelet aggregometry and their clinical usefulness

Resumen Conocer la función plaquetaria y su repercusión en la fisiología y en la generación de enfermedad es importante, así como saber interpretar el estudio de agregometría que hoy es necesario para poder establecer diagnósticos y manejos terapéuticos.

Abstract Learning about platelet function and its impact on physiology and the generation of disease is important, as well as knowing how to interpret the study of aggregometry that is now necessary to integrate diagnoses and therapeutic management.

A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study of the Effects of Tongxinluo Capsules in Acute Coronary Syndrome Patients with High On-Treatment Platelet Reactivity / 中华医学杂志(英文版)

<p><b>Background</b>High platelet reactivity (HPR) during clopidogrel treatment predicts postpercutaneous coronary intervention (PCI) ischemic events strongly and independently. Tongxinluo capsules (TCs) are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome (ACS) patients with HPR.</p><p><b>Methods</b>This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2Yreaction units (PRUs) between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups.</p><p><b>Results</b>Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction (15.8% vs. 24.8%, P = 0.013), especially among patients with one cytochrome P450 2C19 loss of function (LOF) allele (χ= 2.931, P = 0.047). The TC group also had a lower prevalence of HPR (33.3% vs. 54.2%, t = 5.284, P = 0.022) and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein (hsCRP), but the composite prevalence of ischemic events did not differ significantly (χ= 1.587, P = 0.208).</p><p><b>Conclusions</b>In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.</p>

The clinical characteristics and molecular pathogenesis of a variant Glanzmann's thrombasthenia-like pedigree / 中华血液学杂志

Objective: To review the clinical characteristics of a pedigree with inherited hemorrhagic disease to explore its molecular pathogenesis. Methods: The clinical data of the pedigree with inherited hemorrhagic disease were collected. After extracting DNA, next generation sequencing was utilized to detect the potential gene mutation. The changes of RASGRP2 transcript of this proband and his parents were detected using RT-PCR to compare with normal control. Results: The phenotype of the proband in this pedigree with inherited platelet dysfunction and bleeding disorder was similar to variant Glanzmann's thrombasthenia, the maximum aggregations of platelet in response to the physiological agonists including ADP, epinephrine and arachidonic acid were significantly lower, leading to severe spontaneous mucosal bleeding. Integrin αIIbβ3 gene mutation was not detected, but another gene mutation RASGRP2 IVS3-1 stood out. The mutation was homozygous in the proband and heterozygosis in both of his parents. Two transcript types were detected in the proband, without transcripts coding functional RASGRP2 protein, however, his parents had functional transcripts and abnormal transcripts, with the normal transcripts in the majority. Conclusions: The RASGRP2 IVS3-1 gene mutation was responsible for the inherited hemorrhagic disease. The RASGRP2 IVS3-1 gene mutation led to abnormal alternative splicing, without formation of functional RASGRP2 protein. The RASGRP2 protein is at the nexus of calcium-dependent platelet activation and hemostasis after damage of blood vessels. Spontaneous mucosal bleeding was a result of the lack of the functional RASGRP2 protein. This was the first report of RASGRP2 gene mutation resulting in bleeding disorder in China, and also the first report of the mutation type of RASGRP2 IVS3-1.

The clinical characteristics and molecular pathogenesis of a variant Glanzmann’s thrombasthenia-like pedigree / 中华血液学杂志

Objective@#To review the clinical characteristics of a pedigree with inherited hemorrhagic disease to explore its molecular pathogenesis.@*Methods@#The clinical data of the pedigree with inherited hemorrhagic disease were collected. After extracting DNA, next generation sequencing was utilized to detect the potential gene mutation. The changes of RASGRP2 transcript of this proband and his parents were detected using RT-PCR to compare with normal control.@*Results@#The phenotype of the proband in this pedigree with inherited platelet dysfunction and bleeding disorder was similar to variant Glanzmann’s thrombasthenia, the maximum aggregations of platelet in response to the physiological agonists including ADP, epinephrine and arachidonic acid were significantly lower, leading to severe spontaneous mucosal bleeding. Integrin αIIbβ3 gene mutation was not detected, but another gene mutation RASGRP2 IVS3-1 stood out. The mutation was homozygous in the proband and heterozygosis in both of his parents. Two transcript types were detected in the proband, without transcripts coding functional RASGRP2 protein, however, his parents had functional transcripts and abnormal transcripts, with the normal transcripts in the majority.@*Conclusions@#The RASGRP2 IVS3-1 gene mutation was responsible for the inherited hemorrhagic disease. The RASGRP2 IVS3-1 gene mutation led to abnormal alternative splicing, without formation of functional RASGRP2 protein. The RASGRP2 protein is at the nexus of calcium-dependent platelet activation and hemostasis after damage of blood vessels. Spontaneous mucosal bleeding was a result of the lack of the functional RASGRP2 protein. This was the first report of RASGRP2 gene mutation resulting in bleeding disorder in China, and also the first report of the mutation type of RASGRP2 IVS3-1.

Effect of Shenxiong glucose injection on platelet reactivity during aspirin treatment in patients with acute ischemic stroke / 国际脑血管病杂志

Objective To investigate the effect of Shenxiong glucose injection on platelet reactivity during aspirin treatment in patients with acute ischemic stroke.Methods A total of 263 patients with acute ischemic stroke admitted to 12 hospitals from January 2014 to December 2016 were enrolled prospectively.They were randomly divided into aspirin group and aspirin + Shenxiong glucose injection group.The changes of platelet maximum aggregation rate induced by 4 platelet aggregating agents (arachidonic acid,adenosine diphosphate,collagen and platelet activating factor) were detected before and after the treatment.Results There were no significant differences in the demographic data and baseline clinical characteristics between the aspirin group (n =132) and the Shenxiong glucose injection + aspirin group (n =131).At baseline,the maximum aggregation rate of platelet induced by arachidonic acid and platelet activating factor in Shenxiong glucose injection + aspirin group was significantly higher than that in the aspirin group (all P ＜0.05).On the 6th day after treatment,the maximum aggregation rate of platelets induced by the 4 aggregating agents in the Shenxiong glucose injection + aspirin group was significantly lower than that in the aspirin group (all P ＜ 0.001).Conclusion Shenxiong glucose injection had a significant inhibitory effect on platelet reactivity during aspkin treatment in patients with acute ischemic stroke.

Relevant factors of high platelet reactivity during aspirin therapy in patients with ischemic stroke complicated with diabetes / 国际脑血管病杂志

Objective To investigate the changes of platelet reactivity and its influencing factors after aspirin treatment in patients with ischemic stroke complicated with diabetes. Methods From September 2016to December 2017, patients with acute ischemic stroke admitted to the Department of Neurology, Weihai Municipal Hospital within 24 h of onset were enrolled. All patients took aspirin (100 mg/d) within 24 h ofadmission, and after taking the drug (7 ±2 d), the PL-11 platelet function analyzer was used to determine the maximum platelet aggregation ratio (MAR) induced by arachidonic acid (AA). The baseline data of the patients were documented. The factors affecting high platelet reactivity (HPR) were analyzed. Results A total of 398 patients with ischemic stroke were enrolled, including 137 in the diabetes group and 261 in the non-diabetes group. MARAA (43. 45％ ± 14. 11％ vs. 31. 55％ ± 19. 39％; t = 6. 996, P < 0. 001) and the incidence of HPR (34. 3％ vs. 19. 9％; χ2 = 9. 946, P = 0. 002) in the diabetes group were significantly higher than in those in the non-diabetes group. Of the 137 patients with ischemic stroke complicated with diabetes, 47 had HPR. The proportions of patients with hyperlipidemia, previous history of stroke or transient ischemic attack and baseline NIHSS score, HOMA-IR (homeostatis model assessment-insulin resistance),high-sensitivity C-reactive protein, fasting blood glucose, and glycosylated hemoglobin in the HPR group were significantly higher than those in the non-HPR group (all P < 0. 05). Multivariate logistic regression analysis showed that HOMA-IR (odds ratio [OR] 1. 153, 95％ confidence interval [CI] 1. 027-1. 295; P =0. 016), high-sensitivity C-reactive protein (OR 9. 416, 95％ CI 2. 271-39. 049; P = 0. 002), fasting blood glucose (OR 1. 125, 95％ CI 1. 025-1. 235; P = 0. 013), and glycosylated hemoglobin (OR 1. 458, 95％ CI 1. 170-1. 816; P = 0. 001) were the independent risk factors for HPR. Conclusion The platelet reactivity during aspirin therapy in patients with ischemic stroke complicated with diabetes mellitus was high, and platelet activity was associated with multiple mechanisms, such as inflammation, insulin resistance, and hyperglycemia.

Association of α2A-Adrenergic Receptor Genetic Variants with Platelet Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals modifies the antiplatelet response to sympathetic stimulation. The aim of this study was to investigate the effect of ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after undergoing percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms (SNPs) of ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19*2 were detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP) inhibition was detected by thromboelastography (TEG®).</p><p><b>RESULTS</b>The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 (adjusted P = 0.022) and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033), rs3750625 (P = 0.020) and CYP2C19*2 (P = 0.002) were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males, but not in females.</p><p><b>CONCLUSION</b>ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.</p>

Effects of Platelet Number and Platelet Indices on Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor / 대한내과학회지

BACKGROUND/AIMS: Platelet counts and characteristics can influence platelet reactivity during antiplatelet therapy. We compared the effects of both platelet count and indices on platelet reactivity between patients who were treated with either clopodogrel or ticagrelor. METHODS: Patients with coronary artery disease who underwent percutaneous coronary intervention were randomly assigned to either the clopidogrel (n = 63) or ticagrelor (n = 65) groups. Platelet count, platelet indices (including mean platelet volume, platelet distribution width, platelet large cell ratio, and immature platelet fraction), and platelet reactivity were measured before intervention, and 48 hours and 30 days post-intervention. High on-treatment platelet reactivity (HPR) was defined as ≥ 47 unit as assessed by multiple electrode platelet aggregometry. RESULTS: Baseline platelet reactivity was similar between the two groups; however, at 48 hours and 30 days, platelet reactivity was significantly lower in the ticagrelor group than in the clopidogrel group. Platelet count, mean platelet volume, platelet distribution width, platelet large cell ratio, and immature platelet fraction were significantly correlated with platelet reactivity in the clopidogrel group; however, these correlations were attenuated in the ticagrelor group. The use of clopodogrel (hazard ratio [HR] 4.1, 95% confidence interval [CI] 1.4–11.9; p = 0.010) and platelet count (HR 9.7, 95% CI 2.9–32.7; p = 0.001) were independent predictors for 30 day HPR. Platelet count was an independent predictor of HPR in the clopidogrel group but not in the ticagrelor group. CONCLUSIONS: Platelet count and indices are significantly correlated with platelet reactivity. However, antiplatelet treatment with ticagrelor could overcome these associations.