抗血小板治疗后血小板高反应性与急性非心源性脑梗死早期神经功能恶化的关系

目的探讨抗血小板治疗后血小板高反应性(HTPR)与急性非心源性脑梗死早期神经功能恶化(END)的关系。方法入选急性非心源性脑梗死患者215例,根据入院72h内神经功能有无恶化分为END组55例和非END组160例。全部患者入院当日开始口服阿司匹林300 mg后6~24h空腹取血,检测血脂及糖化血红蛋白(HbA1c)等,并以二磷酸腺苷为诱导剂测定血小板聚集功能(PAGT),比较2组HTPR发生率,采用多因素logistic回归分析END的独立危险因素,采用ROC曲线评估PAGT对END的预测价值。结果 END组LDL[(3.23±0.75)mmol/L vs(3.02±0.63)mmol/L]、HbA1c[(6.75±0.65)%vs(6.70±0.54)%]明显高于非END组(P0.01)。END组HTPR发生率明显高于非END组,差异有统计学意义(63.34%vs 43.75%,P=0.011),多因素logistic回归分析显示,LDL、HbA1c和HTPR是急性非心源性脑梗死患者END的独立危险因素(OR=9.023,95%CI:3.085~26.387,P=0.000,OR=11.344,95%CI:3.882~33.152,P=0.000,OR=34.364,95%CI:4.422~267.029,P=0.001,),PAGT判断急性非心源性脑梗死END的ROC曲线下面积为0.864(95%CI:0.806~0.922,P=0.000)。结论 HTPR与急性非心源性脑梗死END密切相关。     

冠心病患者血小板聚集功能与炎症因子关系的研究

目的:探讨冠心病患者血小板聚集功能与炎症因子的关系.方法:按照标准入选150例住院治疗的冠心病患者及53例查体健康人(正常对照组).冠心病患者在基础治疗相同的情况下按美国心脏病学会/美国心脏病协会(ACC/AHA)治疗指南分为稳定性心绞痛(SAP)组47例(阿司匹林100 mg/d),不稳定性心绞痛(UAP)组50例(阿司匹林100 mg/d+达肝素5000U Q12h皮下注射),急性心肌梗死(AMI)组53例(阿司匹林100 mg/d+氯吡格雷75 mg/d+达肝素5000U Q12h皮下注射).正常对照组和所有患者入院即刻肘静脉取血,测定空腹血糖、血脂全项、血常规、血小板最大聚集率、尿11-脱氢-血栓素B_2含量、血浆高敏C反应蛋白(hsCRP).结果:AMI组血浆hsCRP水平高于UAP组[(15.46±8.22)mg/L,(7.61±6.11)mg/L P<0.01)]、UAP组高于SAP组[(7.61±6.11)mg/L,(4.25±2.95)mg/L P<0.01]、SAP组高于正常对照组[(4.25±2.95)mg/L,(2.07±1.28)mg/L P<0.05],差异均有统计学意义.二磷酸腺苷诱导的血小板最大聚集率在UAP组、AMI组显著高于正常对照组及SAP组(P<0.05),UAP组与AMI组间、SAP组与正常对照组间血小板最大聚集率无显著差异(P>0.05).花生四烯酸诱导的血小板最大聚集率和尿11-脱氢-血栓素B_2含量在各组间均有显著差异(P<0.05).血浆hsCRP水平与二磷酸腺苷诱导血小板最大聚集率呈显著的正相关(r=0.473,P=0.000);与花生四烯酸诱导血小板最大聚集率呈显著的正相关(r=0.434,P=0.000);与尿11-脱氢-血栓素B_2的含量呈显著的正相关(r=0.554,P=0.000).结论:冠心病患者体内炎症反应与血小板活化状态存在紧密关联,两者共同影响着冠心病的严重程度和稳定状态,是评价冠心病临床状态的检测指标,早期有效抗血小板治疗和减轻炎症反应会有效控制急性冠脉综合征的发生发展.     

氯吡格雷联合阿司匹林对老年不稳定性心绞痛患者血小板聚集的影响

目的观察氯吡格雷联合阿司匹林对老年不稳定性心绞痛患者血小板聚集功能的影响。方法选择老年不稳定性心绞痛患者120例,随机分为阿司匹林组、低剂量联合组(氯吡格雷25 mg)、中剂量联合组(氯吡格雷50mg)、高剂量联合组(氯吡格雷75 mg),每组30例。观察时间为8周,治疗前后测患者血小板颗粒膜蛋白140(GMP-140)浓度及分别用二磷酸腺苷(ADP)和花生四烯酸(AA)为诱导剂的血小板聚集率,记录临床疗效及不良反应发生情况。结果与治疗前比较,治疗8周后,阿司匹林组、低、中和高剂量联合组GMP-140浓度、ADP介导的血小板聚集率显著降低[(15.3±2.9)μg/L vs(9.7±1.5)μg/L、(16.7±3.4)μg/L vs(8.9±2.3)μg/L、(14.9±3.0)μg/L vs(5.1±1.4)μg/L、(16.4±3.5)μg/L vs(7.8±2.2)μg/L,(43.5±9.8)%vs(24.3±8.9)%、(41.0±7.8)%vs(20.3±8.1)%、(44.3±9.2)%vs(21.5±8.7)%、(43.9±7.6)%vs(20.6±8.0)%,P0.05];AA介导的血小板聚集率4组治疗后较治疗前明显降低[(28.7±9.1)%vs(16.1±7.4)%、(29.2±9.3)%vs(17.2±8.5)%、(30.1±10.1)%vs(17.9±9.4)%、(28.8±8.5)%vs(25.7±8.6)%,P0.05],4组比较无显著差异(P0.05)。低、中、高剂量联合组总有效率均高于阿司匹林组(93.33%、96.67%、96.67%vs 86.67%,P0.05)。仅高联合组出现2例不良反应。结论应用氯吡格雷50mg联合阿司匹林对老年不稳定性心绞痛患者双联抗血小板聚集治疗最为适合。     

急性冠状动脉综合征合并糖尿病患者经皮冠状动脉介入术后替格瑞洛与氯吡格雷抗血小板疗效及预后研究

目的应用血栓弹力图评价替格瑞洛与氯吡格雷在急性冠状动脉综合征(ACS)合并糖尿病(DM)患者经皮冠状动脉介入(PCI)术后抗血小板治疗的疗效和预后。方法入选2016年6月至2017年1月期间在陕西省第四人民医院心血管内科住院治疗的ACS合并DM患者100例。采用前瞻性、随机对照的研究方法,按随机数字表分为两组:氯吡格雷组和替格瑞洛组,每组50例。PCI术后24~48 h行血栓弹力图检测,比较两组花生四烯酸(AA)诱导的血小板抑制率和二磷酸腺苷(ADP)诱导的血小板抑制率以及最大血凝块幅度(MAADP)。术后随访6个月,比较两组主要不良心血管事件(MACE)、出血事件和呼吸困难的发生率。采用SPSS 19.0软件进行数据处理。根据数据类型,分别采用t检验或x~2检验进行组间比较。结果与氯吡格雷组相比,替格瑞洛组AA抑制率[(72.3±26.6)%vs(54.0±31.4)%,P=0.041]和ADP抑制率[(76.5±22.1)%vs(43.4±28.7)%,P=0.016]均显著增高,MAADP幅度显著降低[(33.2±10.5)vs(48.2±13.6)mm,P=0.024]。替格瑞洛组AA抑制率50%(14.0%vs38.0%,P=0.006)和ADP抑制率30%(6.0%vs28.0%,P=0.003)的患者数量显著低于氯吡格雷组。术后6个月替格瑞洛组MACE发生率较氯吡格雷组显著降低(8.2%vs 22.9%,P=0.045);两组出血事件和呼吸困难发生率间差异无统计学意义。结论对于ACS合并DM患者,PCI术后服用替格瑞洛的抗血小板疗效明显优于氯吡格雷。     

血小板高反应性对冠状动脉钙化患者介入术后发生主要不良心血管事件的研究

目的探讨血小板高反应性对冠状动脉钙化患者PCI术后发生主要不良心血管事件(MACE)的预测价值。方法回顾性分析行PCI患者264例,平均随访(367±64)d。根据冠状动脉造影有无靶病变钙化分为钙化组113例和非钙化组151例,所有患者均服用标准双联抗血小板药物(阿司匹林+氯吡格雷)治疗。二磷酸腺苷诱导的血小板高反应性(HPR)定义为血小板聚集率≥50%。结果钙化组患者HPR比例明显高于非钙化组(24.8%vs10.6%,P=0.002)。总体人群HPR患者MACE发生率较非HPR患者明显升高(27.3%vs 5.9%,P=0.000);钙化组HPR患者MACE发生率较非HPR患者明显升高(35.7%vs 7.1%,P=0.001);非钙化组HPR患者与非HPR患者MACE发生率比较,差异无统计学意义(12.5%vs 5.2%,P=0.244)。总体人群和钙化组HPR与MACE呈正相关(r=0.272,r=0.355,P0.01)。非钙化组HPR与MACE无相关性(r=0.095,P=0.245)。HPR对MACE的危险度在总体人群、钙化组、非钙化组分别为OR=5.97(P0.01)、OR=7.31(P0.01)、OR=2.61(P0.05)。结论 HPR对冠状动脉钙化患者PCI术后MACE有一定预测价值。     

原发性血小板增多症伴随轻度骨髓网状纤维增多患者的危险因素

目的:探索伴随骨髓网状纤维增多原发性血小板增多症(essential thrombocythemia, ET)患者的危险因素。方法:将58例ET患者根据是否伴有轻度骨髓网状纤维增多(1级)分为增多组(29例)和无增多组(29例),比较2组患者间基线资料、基因突变、血常规、生化、骨髓细胞学、骨髓活检等指标差异，进一步多因素回归分析影响ET患者伴随轻度骨髓网状纤维增多的独立危险因素。结果:与无增多组比较，增多组患者的TET2突变频率(30.77%vs 8.33%,P=0.048)、血小板计数(PLT)[(820.93±242.95)×10⁹/L vs (673.93±174.00)×10⁹/L,P=0.01]、乳酸脱氢酶[(285.63±97.60) U/L vs(213.46±45.14) U/L,P=0.02]、造血容量[(62.00±15.75)%vs (53.20±12.82)%,P=0.04]、粒系细胞占比[(63.64±8.61)%vs (57.70±8.80)%,P=0.02]、粒红细胞比[(4.01±2.02) vs (2.88±...     

脑微出血部位和负荷与脑梗死抗血小板治疗的相关分析

目的探讨脑微出血(CMB)发生部位和负荷对脑梗死抗血小板治疗风险及获益的影响。方法选择伴CMB的急性脑梗死患者214例,根据CMB发生部位分为单纯脑叶组39例,深部/幕下组62例,混合部位组113例,随访各组新发脑梗死、脑出血情况,并比较各组治疗前及治疗1年后CMB的变化。结果深部/幕下组既往脑梗死、高血压和糖尿病比例明显高于单纯脑叶组和混合部位组(P<0.05)。混合部位组基线CMB数高于单纯脑叶组和深部/幕下组[(8.69±2.75)个vs(6.65±2.47)个、(6.58±3.17)个,P<0.05]。单纯脑叶组脑出血比例明显高于深部/幕下组和混合部位组(12.8%vs 3.2%、2.7%,P<0.05),且发生脑出血患者中4例基线CMB数>5个。深部/幕下组再发脑梗死比例明显高于单纯脑叶组和混合部位组(24.2%vs 7.7%、9.7%,P<0.05)。3组治疗1年后仅部分患者复查头颅MRI,其中单纯脑叶组28例,深部/幕下组40例,混合部位组56例。单纯脑叶组CMB进展比例明显高于深部/幕下组和混合部位组,差异有统计学意义(35.7%vs 12.5%、10.7%,P<0.05),且病灶以脑叶为主。结论抗血小板治疗风险与CMB部位和负荷相关,单纯脑叶CMB抗血小板治疗的脑出血风险增加,治疗后CMB更易进展。深部/幕下CMB患者脑梗死复发风险更高。     

血栓弹力图评价抗血小板治疗的疗效及相关因素分析

目的用血栓弹力图(TEG)的方法评价抗血小板治疗的疗效和相关因素分析。方法选择自愿完成TEG测定的年龄≥60岁军队老年男性955例,按服用抗血小板药物分4组,阿司匹林组368例,氯吡格雷组115例,双联抗血小板药物组(双抗组)43例,无抗血小板药物组429例。用TEG指标评价抗血小板药物的有效性,并用多因素logistics回归分析影响疗效的相关因素。结果阿司匹林组花生四烯酸(AA)途径血小板抑制率(AA抑制率)为(48.0±19.3)%,氯吡格雷组二磷酸腺苷(ADP)途径血小板抑制率(ADP抑制率)为(63.0±18.2)%,双抗组AA抑制率为(51.0±16.5)%,ADP抑制率为(46.0±15.3)%,均在起效范围内。AA途径中,阿司匹林组与双抗组有效率无差异(45.80%vs 51.16%,P0.05),ADP途径中,氯吡格雷组与双抗组有效率无差异(76.52%vs67.44%,P0.05)。多因素logistics分析示,白细胞计数(OR=0.891,P=0.001),肾小球滤过率(OR=1.016,P=0.013)是增加出血的危险因素;血小板计数(OR=1.026,P=0.000),糖化血红蛋白(OR=1.358,P=0.011)是血栓风险增加的危险因素。结论严格质量控制的TEG测定可以作为临床抗血小板治疗疗效的评估手段之一。     

老年冠心病患者血小板-白细胞聚集体的表达及其意义

目的:探讨老年冠心病患者血小板-白细胞聚集体(PLA)的表达及其意义.方法:选择我院内科2010年1月至2012年12月期间收治的冠心病患者162例,分为稳定型心绞痛(SAP)组(92例),急性冠脉综合征(ACS)组(70例),选择同期非冠心病患者80例为正常对照组.比较3组间PLA、血小板-中性粒细胞聚集体(PNA)、血小板淋巴细胞聚集体(PLyA)和血小板-单核细胞聚集体(PMA)的水平,采用Spearman相关分析分析PLA与有关临床指标的相关性.结果:与正常对照组和SAP组比较,ACS组PLA[(2.23±1.20)％比(3.25±2.16)％比(4.36±2.65)％]、PMA[(15.3±7.6)％比(23.5±19.7)％比(32.4±19.6)％]、PNA[(1.85±0.89)％比(2.14±1.56)％比(3.64±4.65)％]和PLyA(1.38±0.78)％比(1.42±0.87)％比(2.06±1.28)％]水平显著升高(P均＜0.01),且SAP组PLA、PMA水平显著高于正常对照组(P＜0.01).Spearman相关性分析显示:冠心病患者PLA与血糖、甘油三酯呈正相关(r1=0.680,P1=0.030;r2=0.738,P2=0.015),与高密度脂蛋白胆固醇呈负相关(r=-0.722,P=0.018).结论:PLA、PMA水平升高提示可能有老年冠心病,甚至是急性冠脉综合征.     

尿酸对老年冠心病患者介入术后凝血及血小板功能的影响

目的探讨血尿酸对老年冠心病患者PCI术后凝血及血小板功能的影响。方法选取行PCI术的老年冠心病患者110例,并按照血清尿酸水平分为高尿酸血症组41例和对照组69例,患者于术后1周行血栓弹力图检测,比较2组患者的凝血功能和血小板二磷酸腺苷(ADP)抑制率(ADP%)、花生四烯酸(AA)抑制率(AA%)。同时记录凝血反应时间(R值)、血凝块形成时间(K值)、血凝块形成的最大幅度(MA值)和血凝块形成的速率(α角)。结果与对照组比较,高尿酸血症组的R值[(5.88±1.50)min vs(7.16±2.06)min,P=0.001]、K值[(2.15±0.63)min vs(2.58±0.88)min,P=0.007]、ADP%[(53.94±24.62)%vs(73.26±18.56)%,P=0.000]、AA%[(60.06±23.43)%vs(79.59±15.98)%,P=0.000]显著降低,MA值[(65.57±3.15)mmvs(59.01±6.99)mm,P=0.000]、α角[(64.69±5.24)°vs(56.51±4.86)°,P=0.000]显著增高。血尿酸与R值、K值、ADP%、AA%呈负相关(P0.05,P0.01),与MA值、α角呈正相关(P0.01)。血尿酸与ADP%、AA%独立负相关(P0.05)。结论合并高尿酸血症的老年冠心病患者PCI术后血液呈高凝状态,血小板活性高,阿司匹林抵抗和氯吡格雷抵抗发生率高。     

血小板输注中抗体检测和配合试验的应用

目的：提高血小板制剂对血小板减少、尤其是血小板输注无效症（PTR）患者的输注疗效,避免宝贵血源的浪费。方法：应用单抗固相微孔板（MASPAT）法检测患者血清中的血小板抗体,进行血小板供者与患者之间的配合试验。结果：2005年6月-2007年11月对109例患者进行了血小板抗体的检测,其中42例患者检出血小板抗体（阳性率38．5％）,对含有血小板抗体的患者经适合性血小板输注后,血小板计数有明显上升。结论：MASPAT法在特异性、敏感性、重复性方面良好,操作快速、简便,判断可靠;易做到规范化,程序化,标准化;据此建立的“适合性血小板输注”对含有血小板抗体的患者是有效的,可用于临床血小板抗体的检测和配合试验。     

Mean platelet volume and mean platelet volume/platelet count ratio in infective endocarditis

Abstract

Infective endocarditis (IE), an infection of the endocardial surface, frequently leads to life-threatening complications, such as thromboembolism due to platelet activation. We investigated the mean platelet volume (MPV) in Korean patients with IE and the serial changes thereof, in comparison with other laboratory parameters. We analyzed 248?MPV results from 22 patients diagnosed with IE in our hospital between January 2011 and April 2012. MPV was measured with an Advia 2120 (Siemens Healthcare Diagnostics, Tarrytown, NY) using EDTA-containing tubes. The mean MPV differed significantly between the patient and control groups, 8.74 vs. 7.96?fl, respectively. In addition, the platelet count and MPV/platelet count ratio were significantly decreased in the patient group. The total platelet mass and platelet size in IE might be increased. Further studies should examine more patients to verify the changes in the MPV and MPV/platelet count ratio in IE and assess in greater detail the relationship between MPV and thrombotic complications caused by platelet activation.     

Phosphorylation of platelet actin-binding protein during platelet activation

In this study we have followed the 32P-labeling of actin-binding protein as a function of platelet activation. Utilizing polyacrylamide- sodium dodecyl sulfate gel electrophoresis to resolve total platelet protein samples, we found 2--3-fold labeling increases in actin-binding protein 30--60 sec after thrombin stimulation. Somewhat larger increases were observed for 40,000 and 20,000 apparent molecular weight peptides. The actin-binding protein was identified on the gels by coelectrophoresis with purified actin-binding protein, its presence in cytoskeletal cores prepared by detergent extraction of activated 32P- labeled platelets, and by direct immunoprecipitation with antibodies against guinea pig vas deferens filamin (actin-binding protein). In addition, these cytoskeletal cores indicated that the 32P-labeled actin- binding protein was closely associated with the activated platelet's cytoskeleton. Following the 32P-labeling of actin-binding protein over an 8-min time course revealed that in aggregating platelet samples rapid dephosphorylation to almost initial levels occurred between 3 and 5 min. A similar curve was obtained for the 20,000 apparent molecular weight peptide. However, rapid dephosphorylation was not observed if platelet aggregation was prevented by chelating external calcium or by using thrombasthenic platelets lacking the aggregation response. Thus, cell-cell contact would seem to be crucial in initiating the rapid dephosphorylation response.     

Inhibition of platelet phospholipid methylation during platelet secretion

A pathway for the synthesis of membrane phosphatidylcholine involving the N-methylation of phosphatidylethanolamine has been detected in several types of mammalian cells. Furthermore, it has been implicated in the coupling of agonist binding to cell response. We examined whether human platelets exhibit this synthetic pathway and whether platelet agonists influence its activity. When washed platelets were incubated with 0.15 microM L-[methyl-3H]methionine at 37 degrees C, they incorporated methyl-3H into their phospholipids linearly at the rate of 1 pmole/10(9) platelets/hr. When incubated with 20 microM radiolabeled methionine, they incorporated about 15 pmole/10(9) platelets/hr. The radioactivity was found predominantly in phosphatidyl- N-monomethylethanolamine, phosphatidyl-N,N-dimethylethanolamine, and phosphatidylcholine. Thrombin caused an immediate (within 15 sec) and sustained (up to 30 min) decrease in the rate and extent of N- methylation of platelet phospholipids. This was accounted for by a decrease in synthesis of methylated phospholipids rather than an increase in their degradation. This thrombin effect correlated with serotonin release and could be dissociated from platelet aggregation and prostaglandin synthesis. Thrombin also decreased the synthesis of phosphatidylcholine when choline was used as the radiolabeled substrate. Other agonists such as epinephrine, adenosine diphosphate (ADP), or A23187 also decreased phospholipid methylation under conditions in which they stimulated serotonin release. These data demonstrate that platelets are capable of synthesizing phosphatidylcholine from phosphatidylethanolamine by N-methylation and that agonists perturb this pathway as they induce platelet secretion. The precise role of phospholipid methylation in either resting or stimulated platelets remains to be established.     

光学法计数在低值血小板检测中的研究应用

目的：评价光学法计数在低值血小板检测中的研究应用。方法：200例低值血小板患者血标本,在血液分析仪上分别进行电阻抗法和光学法血小板计数,同时进行镜检法计数。结果：以镜检法为参考方法,光学法的相关系数为0．994。电阻抗法的相关系数0．921。在小红细胞组、红细胞碎片组和大血小板组,电阻抗法和镜检法计数结果差异有统计学意义（P〈0．05）,光学法和镜检法计数结果差异无统计学意义（P〉0．05）。结论：光学法计数可以满足低值血小板检测准确性的要求,值得临床实验室推广应用。     

Interruption of tumor-associated platelet consumption with platelet enzyme inhibitors

Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus aspirin, RA233, sulfinpyrazone, or a combination of RA233 and sulfinpyrazone) to determine if tumor-related reductions in platelet survival and concentration could be reversed. Anticoagulation was ineffective, while platelet enzyme inhibitors were able to produce improvements in platelet survival. Of the 18 dogs with metastatic tumor treated with platelet enzyme inhibitors, only 5 (28%) showed a reduction in platelet survival during the first week of observation on therapy compared to their baseline survivals. This is significantly different than the decreases in platelet survivals observed in 8 of 10 untreated dogs (80%) with metastatic tumor observed for the same interval. Furthermore, 8 of the 18 treated dogs (44%) had platelet survivals within 2 standard deviations of normal, compared to only 1 of 10 untreated dogs. Of the 8 dogs with normal platelet survivals, 6 were treated with a combination of a phosphodiesterase inhibitor (RA233 or dipyridamole) and a cyclooxygenase inhibitor (sulfinpyrazone or aspirin). The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated. Thus, platelet enzyme inhibitors with different mechanisms of action may have a synergistic effect in reversing the abnormal platelet hemostasis found in a variety of spontaneously occurring canine neoplasms.     

Effect of heparin on platelet count and platelet aggregation

The in vitro effect of heparin on platelet aggregation was studied in three groups: in 26 subjects recently treated with heparin, in 18 subjects on maintenance hemodialysis, and in 20 normal controls. With the aid of Technicon H6000, platelet counts and platelet aggregations were compared in whole blood samples collected in ethylenediaminetetraacetic acid (EDTA) and in heparinized tubes. Although there was no significant difference between platelet count of heparinized and EDTA blood in the control group, the dialysis group and the group recently treated with heparin showed significantly lower platelet counts and more platelet aggregation in heparinized tubes than in EDTA tubes. We speculate that the majority of subjects exposed to heparin develop an antibody or a proaggregator which can aggregate or agglutinate platelets in the presence of heparin and causes destruction of platelets; but only in a small percentage of subjects receiving heparin is this reaction severe enough to cause thrombocytopenia.