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我们真的了解肌钙蛋白吗? 肌钙蛋白1标准品

放大字体  缩小字体 发布日期:2016-10-25  来源:孔较瘦  作者:孔令秋  浏览次数:71
核心提示:portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">前几天查房,病房中有一名自其它科室转科过来的病人。portant; word-wrap

portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">前几天查房,病房中有一名自其它科室转科过来的病人。portant; word-wrap: break-word !important;">该患者既往无高血压、糖尿病、吸烟等冠心病危险因素,平时生活规律。本次因活动后气紧入院,初步诊断为肺部感染。入院后多份心电图无异常,但心肌损伤标志物提示肌钙蛋白明显升高,并伴有BNP升高,故考虑为心肌梗死。给予抗凝、抗血小板、利尿等处理。患者无任何好转,遂邀请心内科会诊,并要求转入心内科继续治疗心肌梗死。portant; word-wrap: break-word !important;">结合其呼吸道感染病史、入院后有腹泻症状、加之超声提示左心室整体搏幅均降低,且心电图和心肌损伤标志物无动态演变,故考虑为急性心肌炎,经甲强龙等治疗后迅速好转。

portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">

portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">该病例具备很好的警示作用,portant; word-wrap: break-word !important;">飙升的肌钙蛋白让很多医师忽视了病史采集的和病情分析的重要性。让人产生了一叶障目,不见泰山之感。portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">随着临床检验技术的进步,肌钙蛋白检测敏感性越来越高,这对于早期识别心肌梗死和改善预后大有裨益。portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">敏感性提高在减少漏诊的同时,使得许多非心肌梗死的患者误诊为心肌梗死,并接受了相关治疗。在portant; word-wrap: break-word !important;">高敏感肌钙蛋白portant; word-wrap: break-word !important;">大行其道的形势下,科学的解读肌钙蛋白升高,大有必要。


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portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">一、有关心肌梗死定义版本的更新

portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">若要诊断心肌梗死,孔较瘦认为首先要理解心肌梗死的确切定义。

portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">有关心肌梗死的portant; word-wrap: break-word !important;">最早定义始于1979年,由世界卫生组织(WHO)发起并推广,portant; word-wrap: break-word !important;">其后于2000年,由欧洲心脏病学会(ESC)、美国心脏病学基金会(ACCF)进行了更新。portant; word-wrap: break-word !important;">时隔七年,再次由ESC、ACCF联合美国心脏学会 (AHA)和世界心脏联盟(WHF)共同发起,对全球心肌梗portant; word-wrap: break-word !important;">死的定义进行了更新。因为该定义发起和制定时,世界四大心脏病学组织都没有想跟中国专家商量的意思,在无法表达意见的基础上,我们只得接受该定义。所以在2008年,由中华医学会心血管病分会和中华心血管病杂志联合倡议我国也采纳这一最新定义。人算不如天算,2007年的定义我们还没有完全背诵下来,portant; word-wrap: break-word !important;">2012年8月在德国慕尼黑召开的ESC大会上,欧美专家再次更新了心肌梗死全球统一定义。与之前强调缺血性胸痛、心肌损伤标志物和心电图动态演变不同,此次新版定义的心肌梗死标准为:血清心肌标志物(主要是肌钙蛋白)升高(至少超过99%参考值上限),并至少伴有以下一项临床指标:

  • portant; word-wrap: break-word !important; clear: both; min-height: 1em; white-space: pre-wrap; text-indent: 0em;">portant; word-wrap: break-word !important;">缺血症状;

  • portant; word-wrap: break-word !important; clear: both; min-height: 1em; white-space: pre-wrap; text-indent: 0em;">portant; word-wrap: break-word !important;">新发生的缺血性ECG改变[新的ST-T改变或左束支传导阻滞];

  • portant; word-wrap: break-word !important; clear: both; min-height: 1em; white-space: pre-wrap; text-indent: 0em;">portant; word-wrap: break-word !important;">ECG病理性Q波形成;

  • portant; word-wrap: break-word !important; clear: both; min-height: 1em; white-space: pre-wrap; text-indent: 0em;">portant; word-wrap: break-word !important;">影像学证据显示有新的心肌活性丧失或新发的局部室壁运动异常;

  • portant; word-wrap: break-word !important; clear: both; min-height: 1em; white-space: pre-wrap; text-indent: 0em;">portant; word-wrap: break-word !important;">冠脉造影或尸检证实冠状动脉内有血栓。

    portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">2012年全球心肌梗死统一定义中,仍将心肌梗死分为以下5型portant; word-wrap: break-word !important;">:portant; word-wrap: break-word !important;">    

    • portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">1型:portant; word-wrap: break-word !important;">由冠状动脉斑块破裂、裂隙或夹层引起冠脉内血栓形成,从而导致自发性心肌梗死;

    • portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">2型:portant; word-wrap: break-word !important;">继发于心肌氧供需失衡(如冠脉痉挛、心律失常portant; word-wrap: break-word !important;">、贫血、呼衰、高血压portant; word-wrap: break-word !important;">或低血压)导致缺血的心肌梗死;

    • portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">3型:portant; word-wrap: break-word !important;">疑似为心肌缺血的突发心源性死亡,或怀疑为新发生的ECG缺血变化或新的LBBB的心源性死亡。由于死亡已经发生,患者来不及采集血样进行心肌标志测定。

    • portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">4型(4a和4b):portant; word-wrap: break-word !important;">与PCI相关的心肌梗死,其中将4型心肌梗死分为4a型和4b型;4a型心梗定义为PCI过程所致的心肌梗死,包括球囊扩张和支架植入过程,标准是:术后患者血清肌钙蛋白水平升高超过99%参考值上限的5倍,并且有其中之一:心肌缺血症状、新的ECG缺血变化、造影所见血管缺失、有新的心肌活力丧失或新的室壁运动异常的影像学证据。4b型心梗定义为支架血栓形成的心肌梗死,标准是:冠脉造影或尸检所见有缺血相关血管有血栓形成,血清心肌标志物升高至少超过99%参考值上限。

    • portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">5型:portant; word-wrap: break-word !important;">与冠状动脉搭桥手术相关的心肌梗死。患者的肌钙蛋白要超过99%参考值上限10倍,并伴有一下之一:ECG新出现的病理性Q波或LBBB、造影证实新的桥(静脉桥或动脉桥)内堵塞、新的心肌活性丧失或新发的局部室壁运动异常。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">二、临床对肌钙蛋白升高解读的现状

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">肌钙蛋白升高意味着什么?首选答案肯定是急性心肌梗死,前几年这样回答没问题,现在由于“高敏肌钙蛋白”“超敏肌钙蛋白”的出现,这样回答就不准确了。下面这张“三车追尾车祸现场”照片,很形象地讲述了高敏感肌钙蛋白检测目前所出portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">现的局面。

      portant; word-wrap: break-word !important;">我们真的了解肌钙蛋白吗?portant; max-width: 100%; box-sizing: border-box !important; word-wrap: break-word !important; visibility: visible !important; width: 500px !important;" alt="" />

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">跑在最前面的车代表检验科,最后面的车代表其它临床科室,中间受夹击的车代表心内科。也就是说,portant; word-wrap: break-word !important;">检验科使用“高敏感肌钙蛋白检测试剂”检测出许多“阳性”患者,其它临床科室科通过肌钙蛋白检测的“阴/阳性”以排除/诊断AMI,而心内科则由于肌钙蛋白“阳性”而不恰当地收了一些“不该收”的患者。准确地讲,这些患者本身身体存在病变,但不能因为只要是肌钙蛋白升高就一律归为心肌梗死。

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">造成以上结果的原因,关键还是交流不够。临床医生对高敏肌钙蛋白新知识的学习了解不够;检验科主动走入临床的宣传交流不够。再加上还有一些检验科的质量存在问题,不能时刻保证结果的精确和可控等。

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">这些问题几年前在欧洲已出现过,美国食品和药物管理局(FDA)马上要批准其投入临床,也会遇到这些问题。但美国人在正式使用前做了许多工作,形成一些“共识”,最主要的目的是portant; word-wrap: break-word !important;">:portant; word-wrap: break-word !important;">要先让临床医生知道如何最佳地应用及对结果进行科学合理的解释。

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">在我国,许多医院已使用高敏肌钙蛋白检测试剂有多年,遇到了越来越多的问题。如何规避一些问题,如何统一认识?我们认为,检验与临床应该加强学习、交流,借鉴欧美经验,避免走弯路或回头路,尽快形成共识。portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important; font-size: 10.5pt; font-family: Arial;">

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;"> 


      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">三、portant; word-wrap: break-word !important;">高敏肌钙蛋白检测在portant; word-wrap: break-word !important;">AMIportant; word-wrap: break-word !important;">诊断中的作用portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important; font-size: 10.5pt; font-family: Arial;">

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">随着医学的不断进步,心肌梗死或损伤标志物也在不断变化发展。从“传统的心肌酶谱”到曾经的“金标准”CK-MB,再到目前为止最特异的心肌损伤/坏死标志物--肌钙蛋白T/I;portant; word-wrap: break-word !important;">从曾经的“心肌梗死标志物”到“心肌损伤标志物”;从单纯的心肌梗死诊断到急性冠状动脉综合征(ACS)及危险分层概念的提出,肌钙蛋白在心肌梗死中诊断和预后判断中的价值日渐上升。

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">我们真的了解肌钙蛋白吗?portant; max-width: 100%; box-sizing: border-box !important; word-wrap: break-word !important; line-height: 1.75em; text-indent: 24pt; visibility: visible !important; width: 404px !important;" alt="" />

      portant; word-wrap: break-word !important;">我们真的了解肌钙蛋白吗?portant; max-width: 100%; box-sizing: border-box !important; word-wrap: break-word !important; visibility: visible !important; width: 411px !important;" alt="" />

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">2012portant; word-wrap: break-word !important;">年第3portant; word-wrap: break-word !important;">版“portant; word-wrap: break-word !important;">心肌梗死诊断全球定义”portant; word-wrap: break-word !important;">再次强调:心血管标志物检测(最好是肌钙蛋白)升高和(或)降低,至少1portant; word-wrap: break-word !important;">次测定值超过第99portant; word-wrap: break-word !important;">百分位的数值,伴有下列至少一项:缺血症状;ECCportant; word-wrap: break-word !important;">改变;影像学证据。把肌钙蛋白检测作为诊断MIportant; word-wrap: break-word !important;">的首选及必要条件,portant; word-wrap: break-word !important;">请大家自觉体会portant; word-wrap: break-word !important;">“portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">超过第portant; word-wrap: break-word !important;">99portant; word-wrap: break-word !important;">百分位的数值”的具体含义,portant; word-wrap: break-word !important;">有人对我说是升高十倍,有人说升高一倍,还有人说达到上限就应该诊断;请大家务必思考一下,portant; word-wrap: break-word !important;">为何这么高级的指南不给大家规定一个具体的数值,比如白细胞数量一样,升高到某个具体数目便为异常?portant; word-wrap: break-word !important; font-family: Arial;">

      portant; word-wrap: break-word !important;">我们真的了解肌钙蛋白吗?portant; max-width: 100%; box-sizing: border-box !important; word-wrap: break-word !important; visibility: visible !important; width: 670px !important;" alt="" />

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">我们必须知道:portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">肌钙蛋白是实验室对心肌坏死/portant; word-wrap: break-word !important;">损伤的检测,而portant; word-wrap: break-word !important;">心肌梗死portant; word-wrap: break-word !important;">是临床诊断。portant; word-wrap: break-word !important;">所有portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">任何实验室检测结果的解释都不能脱离临床背景。不要忘记:hs-cTn应用到临床的主要挑战是不恰当的检测及对结果不正确的解读,而不是标志物本身。portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important; font-family: Arial;">

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">诊断ACSportant; word-wrap: break-word !important;">的基石仍然是完整和详细的病史,心电图和cTnportant; word-wrap: break-word !important;">的结合是当前诊断的核心。一句话“portant; word-wrap: break-word !important;">临床背景是关键”portant; word-wrap: break-word !important;">。用好了,才会在解渎、诊断、危险分层及患者管理等方面“portant; word-wrap: break-word !important;">游刃有余”。

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;"> 


      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">四portant; word-wrap: break-word !important;">、肌钙蛋白升高portant; word-wrap: break-word !important;">还portant; word-wrap: break-word !important;">与哪些疾病相关portant; word-wrap: break-word !important;">?

      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">《美国心脏病学基金会杂志,JACC》曾发表了“解读肌钙蛋白升高临床实践意义的专家共识”,以指导临床医师何时进行肌钙蛋白检测以及如何解读其结果。该共识强调纠正目前“只管后果,不管过程”的惯性思维,portant; word-wrap: break-word !important;">必须知道高敏肌钙蛋白升高的原因归因于四个方面:1型心肌梗死或2型心肌梗死;非ACS急性病情状况;或非ACS慢性病情状况。portant; word-wrap: break-word !important; font-size: 10.5pt; font-family: Arial;">

      portant; word-wrap: break-word !important;">我们真的了解肌钙蛋白吗?portant; max-width: 100%; box-sizing: border-box !important; word-wrap: break-word !important; visibility: visible !important; width: 670px !important;" alt="" />


      portant; word-wrap: break-word !important; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;"> portant; word-wrap: break-word !important;">非心肌缺血性急性心肌损伤主要有下列情况:

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">1.由于cTn具有心脏特异性,而且在正常人血清中含量极低,所以在急性冠脉综合征初期,cTn检测对微小心肌损伤的诊断灵敏度极高。诊断应结合患者的既往病史、高危因素、心电图变化、其他检验指标以及相关影像学检查。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">2.portant; word-wrap: break-word !important;">心力衰竭患者cTn轻度增高,可作为判断临床预后的指标。cTn升高与急、慢性心力衰竭患者左室射血分数降低显著相关,并与心衰严重程度和预后相关。这是因为缺血性或非缺血性心肌细胞死亡或凋亡会导致心肌细胞进行性丧失,从而引起心衰加重,而心肌细胞损伤也会引起cTn升高。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">3.portant; word-wrap: break-word !important;">射频消融治疗的心律失常患者血清cTn可轻度升高,检测多为弱阳性,其原因是高频消融、体外电转直接损伤心肌引起cTn升高,但这种升高无预后判断意义。
           4.portant; word-wrap: break-word !important;">经皮冠状动脉介入(PCI)治疗后往往发现患者cTn轻度升高,心脏手术后也总伴有轻度cTn升高,这些cTn无疑来源于心脏,但其病理机制和预后意义仍然不明确。另外,冠状动脉搭桥(CABG)围手术期心肌梗死和“正常”心肌细胞损伤(如不完全心脏保护、灌注损伤和直接外科损伤)引起的cTn升高很难区分。
           5.portant; word-wrap: break-word !important;">在病毒性心肌炎急性期,患者血清cTn阳性率达88.9%、34%的心肌炎患者伴有cTn升高。另外,急性心包炎也可表现为cTn升高,虽然心包无cTn,但病变累及壁层心肌也会引起这种变化。
           6.具有portant; word-wrap: break-word !important;">心脏毒性的化疗药物也会导致cTn升高,原因是药物毒副作用可引起心肌缺血、心内膜纤维化、心肌病和心包炎。
           7.portant; word-wrap: break-word !important;">心脏浸润性疾病(如淀粉样变性和硬皮病)可侵及心肌心包外间质,心肌细胞受挤压会连续释放cTn。
           8.portant; word-wrap: break-word !important;">心肌钝性损伤可引起致命的心律失常、心衰,往往伴有cTn升高。
           9.portant; word-wrap: break-word !important;">肾功能衰竭和终末期肾病时cTn可达较高峰值,并且cTn升高可长期存在。如果终末期肾病患者在出现急性心脏事件前已有cTn升高,则需有重复检查示明显的cTn升高才能确定急性心肌缺血。 
           10. portant; word-wrap: break-word !important;">cTn仅在剧烈运动时升高,对运动员测定血清cTnI浓度可避免检测肌酸激酶同功酶(CK-MB)可能导致的假阳性结果,有助于监护运动量。
           11.由于cTn阳性定义为高于参考值99百分位,因此1%正常健康人群也可有轻度的cTn升高。但临床上常出现冠心病被错误地解释为假阳性,须通过冠状动脉造影得出最后确诊。
           12.还需注意除外其他原因引起的cTn升高,包括portant; word-wrap: break-word !important;">主动脉夹层或肥厚型心肌病、甲状腺功能减退、心尖球形综合征、横纹肌溶解伴心肌损伤以及败血症、重症肺炎、烧伤等严重病变。 

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">我们真的了解肌钙蛋白吗?portant; max-width: 100%; box-sizing: border-box !important; word-wrap: break-word !important; visibility: visible !important; width: 670px !important;" alt="" />

      portant; word-wrap: break-word !important;"> 


      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">五、小结

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">1、肌钙蛋白升高提示心肌损伤,对心梗并非特异性,可见于多种疾病。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">2、鉴别诊断要综合临床病史、心电图、肌钙蛋白动态变化来明确诊断。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">3、无论何种疾病,肌钙蛋白水平升高都提示预后不良。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">4、应当强调的是要做好对肌钙蛋白检测方法的质量控制。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">5、从心肌梗死分型可以看出,冠状动脉造影并非心肌梗死诊断金标准。

      portant; word-wrap: break-word !important;">portant; word-wrap: break-word !important;">6、心肌梗死是临床诊断,非实验室诊断、非心电图诊断、更非影像学诊断。

       
 
 
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