胡京敏，趙 燦，郭丹杰

?

改良Geneva量表及其聯(lián)合血漿D?二聚體對(duì)老年肺栓塞診斷價(jià)值的探討

胡京敏，趙 燦，郭丹杰*

（北京大學(xué)人民醫(yī)院心臟中心，北京 100044）

評(píng)價(jià)改良Geneva量表及其聯(lián)合血漿D?二聚體對(duì)老年患者肺栓塞（PE）的快速床旁診斷及排除價(jià)值。2009年1月至2014年4月在北京大學(xué)人民醫(yī)院因胸痛、呼吸困難等癥狀被疑診PE的患者276例，分為老年組（≥60歲）和非老年組（＜60歲），以CT肺動(dòng)脈造影（CTPA）為確診金標(biāo)準(zhǔn)。按照改良Geneva量表分為PE低度可能性、中度可能性及高度可能性，同時(shí)檢測(cè)血漿D?二聚體。分析兩組患者臨床特征，比較改良Geneva量表、血漿D?二聚體、改良Geneva量表聯(lián)合血漿D?二聚體在兩組患者中的診斷及排除診斷價(jià)值，其診斷預(yù)測(cè)價(jià)值用受試者工作特征（ROC）曲線下面積（AUC）進(jìn)行評(píng)價(jià)。276例疑診PE患者，經(jīng)CTPA確診PE 80例（≥60歲52例，＜60歲28例）。運(yùn)用ROC曲線評(píng)價(jià)改良Geneva量表對(duì)PE的診斷價(jià)值，老年組與非老年組AUC分別為0.974（95% CI：0.940～0.992），0.981（95% CI：0.924～0.998），差異有統(tǒng)計(jì)學(xué)意義（＜0.001）。老年組血漿D?二聚體、改良Geneva量表聯(lián)合血漿D?二聚體診斷PE的陰性預(yù)測(cè)值分別為93.8%，100.0%；非老年組分別為88.9%，100.0%。老年P(guān)E患者臨床特征不典型；改良Geneva量表對(duì)老年P(guān)E患者的診斷價(jià)值低于非老年患者；對(duì)于老年及非老年疑診PE患者，改良Geneva量表聯(lián)合血漿D?二聚體均可安全排除PE，其價(jià)值優(yōu)于單獨(dú)檢測(cè)血漿D?二聚體。

老年人；肺栓塞；改良Geneva量表；血漿D?二聚體

肺栓塞（pulmonary embolism，PE），為內(nèi)源性或外源性栓子堵塞肺動(dòng)脈或其分支引起肺循環(huán)障礙的臨床病理生理綜合征，包括肺血栓栓塞（pulmonary thromboembolism，PTE）、脂肪栓塞、羊水栓塞、空氣栓塞等。PTE為PE最常見(jiàn)類型，占PE中的絕大多數(shù)，通常所稱的PE即指PTE。PE臨床表現(xiàn)無(wú)特異性[1]，未經(jīng)治療的PE，死亡率高達(dá)30%[2]，早期診斷及治療能降低PE的死亡率[3]，其臨床表現(xiàn)無(wú)特異性，易漏診誤診，老年患者因合并心肺疾病引起誤診率和漏診率增高[4?6]。改良Geneva量表[7]是經(jīng)過(guò)驗(yàn)證的準(zhǔn)確診斷PE的重要方法，但該量表在我國(guó)老年患者的研究尚少。血漿D?二聚體＜500μg/L常被用來(lái)作為PE的排除標(biāo)準(zhǔn)，本研究旨在明確老年可疑PE患者，改良Geneva量表診斷PE及其聯(lián)合血漿D?二聚體快速床旁排除PE診斷的價(jià)值。

1 對(duì)象與方法

1.1 對(duì)象

2009年1月至2014年4月在北京大學(xué)人民醫(yī)院因胸痛、呼吸困難等癥狀被疑診PE的患者276例。其中老年組（≥60歲）187例，男性99例，女性88例，年齡60～93（75.2±7.4）歲；非老年組（＜60歲）89例，男性52例，女性37例，年齡18～59（44.9±10.7）歲。

1.2 方法

1.2.1 研究對(duì)象 所有可疑PE患者記錄性別、年齡、主要癥狀（突發(fā)呼吸困難、胸痛、咯血、暈厥、單側(cè)下肢疼痛）和體征（心率、呼吸頻率、單側(cè)下肢水腫或深壓痛）、危險(xiǎn)因素（既往深靜脈血栓、既往PE、惡性腫瘤、4周內(nèi)骨折、4周內(nèi)制動(dòng)或手術(shù)）。應(yīng)用改良Geneva量表對(duì)疑診PE患者進(jìn)行評(píng)分[8]，0～3分為低度可能，4～10分為中度可能，≥11分為高度可能（表1）。

1.2.2 CT肺動(dòng)脈造影（computed tomography pulmonary arteriography，CTPA） 應(yīng)用美國(guó)GE Healthcare 64排探測(cè)器螺旋CT（lightspeed VCT）掃描。CTPA掃描參數(shù)為：120kV、300mA，準(zhǔn)直器寬度20mm，球管旋轉(zhuǎn)1周0.5s，圖像矩陣為512×512。在GE AW4.2工作站中以1.25mm層厚，1mm間隔按標(biāo)準(zhǔn)方法重建后分析CTPA圖像。

1.2.3 血漿D?二聚體檢測(cè) 入院24h內(nèi)抽血，采用免疫比濁法測(cè)定血漿D?二聚體水平，以≥500μg/L為陽(yáng)性，＜500μg/L為陰性。

表1 改良Geneva量表

DVT: deep vein thrombosis; PE: pulmonary embolism

1.3 統(tǒng)計(jì)學(xué)處理

2 結(jié) 果

2.1 老年組和非老年組PE患者的臨床特征比較

276例疑診PE患者，最終經(jīng)CTPA確診PE 80例，其中老年組52例（65.1%），非老年組28例（34.9%）。對(duì)80例確診的PE患者臨床特征進(jìn)行分析，表2結(jié)果顯示，老年P(guān)E患者呼吸困難發(fā)生率高于非老年患者（＝0.001）；胸痛、咯血、單側(cè)下肢疼痛發(fā)生率低于非老年患者（＝0.008；＝0.018；＝0.002）；老年P(guān)E患者呼吸頻率較非老年患者有增高趨勢(shì)，但差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05）；老年P(guān)E患者心率低于非老年患者，差異亦無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05）；動(dòng)脈血氧飽和度低于非老年患者（＝0.028）；其余指標(biāo)差異均無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05），提示老年P(guān)E患者癥狀缺乏特異性。

2.2 Geneva量表對(duì)老年患者PE的診斷價(jià)值

以CTPA為診斷PE的金標(biāo)準(zhǔn)，用改良Geneva量表對(duì)疑診PE患者進(jìn)行評(píng)分，比較其對(duì)老年組和非老年組PE的診斷價(jià)值。老年組經(jīng)改良Geneva量表評(píng)估為“高度可能PE”的3例患者中經(jīng)CTPA確診2例，誤診率為33.3%（1/3）；61例“低度可能PE”患者中仍有15例經(jīng)CTPA確診為PE，漏診率為24.6%（15/61）。非老年組“高度可能PE”的9例患者中經(jīng)CTPA確診7例，誤診率為22.2%（2/9）；35例“低度可能PE”患者中經(jīng)CTPA確診7例，漏診率為20.0%（7/35）。經(jīng)統(tǒng)計(jì)學(xué)分析，僅通過(guò)改良Geneva量表診斷老年P(guān)E的價(jià)值與非老年患者相似（＞0.05；表3）。

表2 老年與非老年P(guān)E患者的臨床特征

PE: pulmonary embolism; COPD: chronic obstructive pulmonary disease. 1mmHg＝0.133kPa

此外，進(jìn)一步運(yùn)用ROC曲線評(píng)估改良Geneva量表對(duì)PE的診斷價(jià)值。老年組改良Geneva量表ROC曲線見(jiàn)圖1，AUC為0.974（95% CI：0.940～0.992），非老年組改良Geneva量表ROC曲線見(jiàn)圖2，AUC為0.981（95% CI：0.924～0.998），老年組低于非老年組，＝-1.965，＝0.035，兩者之間差異有統(tǒng)計(jì)學(xué)意義。提示改良Geneva量表對(duì)老年P(guān)E患者的診斷價(jià)值低于非老年患者。

2.3 血漿D?二聚體對(duì)老年和非老年患者PE的排除價(jià)值

檢測(cè)血漿D?二聚體，比較其對(duì)兩組疑診PE的排除價(jià)值。老年組61例血漿D?二聚體＜500μg/L的患者中，57例經(jīng)CTPA排除PE診斷，提示血漿D?二聚體診斷老年P(guān)E的陰性預(yù)測(cè)值為93.4%；非老年組27例血漿D?二聚體＜500μg/L的患者中24例經(jīng)CTPA排除PE診斷，對(duì)非老年患者PE的陰性預(yù)測(cè)值為88.9%。

2.4 改良Geneva量表聯(lián)合血漿D?二聚體對(duì)老年患者PE的排除價(jià)值

老年組改良Geneva量表≤3分且血漿D?二聚體＜500μg/L的61例患者中經(jīng)CTPA全部除外PE診斷，非老年組27例患者中經(jīng)CTPA全部除外PE診斷，提示改良Geneva量表≤3分聯(lián)合血漿D?二聚體＜500μg/L對(duì)老年和非老年P(guān)E診斷的陰性預(yù)測(cè)值均為100%?？梢?jiàn)兩組患者中兩項(xiàng)指標(biāo)聯(lián)合對(duì)PE的除外價(jià)值均高于單獨(dú)血漿D?二聚體＜500μg/L。

3 討 論

隨年齡增長(zhǎng)，PE的發(fā)生率和死亡率明顯增加[8]。我國(guó)老年定義為≥60歲，且符合中國(guó)老年醫(yī)學(xué)會(huì)1995年提出的10點(diǎn)建議。老年患者合并多種疾病如呼吸系統(tǒng)疾病等，這些疾病的癥狀、體征與PE易混淆，容易誤診為PE，另外，老年人心肺功能差及受合并疾病的影響，導(dǎo)致發(fā)生PE時(shí)癥狀不典型，容易漏診[4?6]。本研究276例患者，196例疑診PE，但最終均經(jīng)CTPA除外，早期誤診率較高。所以尋找快速診斷及除外PE的診斷方法至關(guān)重要。

有研究報(bào)道，改良Geneva量表聯(lián)合D?二聚體診斷PE更準(zhǔn)確[9]。該量表主要包括：下肢靜脈血栓形成的危險(xiǎn)因素、PE的主要癥狀及體征，有助于對(duì)可疑PE患者進(jìn)行床旁快速的可能性評(píng)估，且不受臨床醫(yī)師的主觀影響，依據(jù)量表評(píng)分將患者分為低度、中度、高度可能PE，國(guó)外有文獻(xiàn)報(bào)道其具有一定的臨床預(yù)測(cè)價(jià)值[10]。本研究以CTPA為確診PE的金標(biāo)準(zhǔn)，應(yīng)用改良Geneva量表對(duì)老年和非老年患者進(jìn)行評(píng)分，證實(shí)該量表對(duì)老年患者診斷價(jià)值與非老年患者相似。ROC曲線是將檢驗(yàn)指標(biāo)的敏感度與特異度以圖示方法結(jié)合，可準(zhǔn)確反映二者關(guān)系，AUC越大，診斷準(zhǔn)確性越高。本研究運(yùn)用ROC曲線評(píng)價(jià)改良Geneva量表對(duì)老年組PE的診斷價(jià)值，結(jié)果顯示老年組ROC的AUC低于非老年組，即改良Geneva量表在老年P(guān)E患者中的診斷價(jià)值受限，這可能是由于老年患者的臨床表現(xiàn)缺乏特異性所致。

PE: pulmonary embolism; CTPA: computed tomography pulmonary arteriography.*Clinical probability of PE categorized by revised Geneva score: low probability: 0?3; medium probability: 4?10; high probability: ≥11.#PE was definitely diagnosed by CTPA

圖1 改良Geneva量表預(yù)測(cè)老年P(guān)E的ROC曲線

Figure 1 The ROC curve of revised Geneva score for prediction of elderly PE ROC: receiver operating characteristics; PE: pulmonary embolism

圖2 改良Geneva量表預(yù)測(cè)非老年組PE的ROC曲線

Figure 2 The ROC curve of revised Geneva score for prediction of non-elderly PE ROC: receiver operating characteristics; PE: pulmonary embolism

血漿D?二聚體作為交聯(lián)纖維蛋白在纖溶系統(tǒng)作用下產(chǎn)生的可溶性降解產(chǎn)物，其水平增高反映機(jī)體高凝狀態(tài)和繼發(fā)性纖溶亢進(jìn)，常見(jiàn)于靜脈血栓栓塞[11]。高齡、肌酐水平升高及合并心肌梗死、感染、手術(shù)、腫瘤等均可導(dǎo)致D?二聚體升高，老年患者上述危險(xiǎn)因素和疾病的發(fā)病率均明顯增加，使其診斷的敏感度和特異度降低[8]。目前主要將血漿D?二聚體水平作為PE的除外標(biāo)準(zhǔn)，但其陰性預(yù)測(cè)值僅約94%[12]，仍存在假陰性可能。本研究顯示在老年P(guān)E患者血漿D?二聚體的陰性預(yù)測(cè)值為93.4%，非老年組為88.9%，與其他報(bào)道一致。

有薈萃分析[13]表明，經(jīng)Geneva量表或改良Geneva量表評(píng)估為“低、中度可能PE”同時(shí)D?二聚體水平正常可安全除外PE。我們的研究也得出了類似的結(jié)果，在本研究中老年組改良Geneva量表≤3分聯(lián)合D?二聚體＜500μg/L可將診斷的陰性預(yù)測(cè)值提高至100%。國(guó)外有研究報(bào)道，Wells量表≤4分聯(lián)合血漿D?二聚體＜500μg/L可將診斷的陰性預(yù)測(cè)值提高至100%[14,15]，表明在診斷PE方面，改良的Geneva量表和Wells量表具有同樣的價(jià)值，這與Douma等[16]的研究一致。但是Wells量表中的1項(xiàng)指標(biāo)“除PE外其他診斷可能性小”具有很大的主觀性且易受量表中其他變量的影響，降低了其診斷價(jià)值和可重復(fù)性。改良Geneva量表則采用完全客觀的指標(biāo)進(jìn)行評(píng)分，方法簡(jiǎn)單且不易受主觀因素的影響。

總之，與非老年患者相比，改良Geneva量表對(duì)PE診斷價(jià)值有限，應(yīng)綜合評(píng)估患者的癥狀、體征及危險(xiǎn)因素，在以往患有PE，呼吸困難，下肢疼痛，有心血管基礎(chǔ)病史時(shí)應(yīng)尤為注意。除外PE時(shí)，改良Geneva量表≤3分聯(lián)合血漿D?二聚體＜500μg/L對(duì)老年P(guān)E的陰性預(yù)測(cè)值高于單獨(dú)血漿D?二聚體＜500μg/L，可用于老年患者快速除外PE診斷，減少不必要的影像學(xué)檢查。本研究為單中心，小樣本研究，可能存在偏差，仍需多中心，大樣本資料進(jìn)一步驗(yàn)證。

[1] Guo DJ, Hu DY, Zhou WR. Clinical analysis on diagnosis and treatment of acute pulmonary embolism[J]. Chin J Cardiol, 2003, 31(1): 49?51. [郭丹杰, 胡大一, 周偉榮. 急性肺栓塞診斷治療的臨床分析及探討[J]. 中華心血管病雜志, 2003, 31(1): 49?51.]

[2] Carson JL, Kelley MA, Duff A,. The clinical course of pulmonary embolism[J]. N Engl J Med, 1992, 326(19): 1240?1245.

[3] Go AS, Mozaffarian D, Roger VL,. Heart disease and stroke statistics—2014 update: a report from the American Heart Association[J]. Circulation, 2014, 129(3): e28?e292.

[4] Liu CP, Li XM, Chen HW,. Depression, anxiety and influencing factors in patients with acute pulmonary embolism[J]. Chin Med J(Engl), 2011, 124(16): 2438?2442.

[5] Osório J. New D-dimer cut-off value helps to rule out pulmonary embolism in the elderly[J]. Nat Rev Cardiol, 2010, 7(7): 358.

[6] Guo Z, Ma Q, Zheng Y,. Normal blood D-dimer concentrations: do they exclude pulmonary embolism[J]? Chin Med J(Engl), 2014, 127(1): 18?22.

[7] Le Gal G, Righini M, Roy PM,. Prediction of pulmonary embolism in the emergency department: the revised Geneva score[J]. Ann Intern Med, 2006, 144(3): 165?171.

[8] Stein PD, Hull RD, Kayali F,. Venous thromboembolism according to age: the impact of an aging population[J]. Arch Intern Med, 2004, 164(20): 2260?2265.

[9] Chagnon I, Bounameaux H, Aujesky D,Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism[J]. Am J Med, 2002, 113(4): 269?275.

[10] Klok FA, Karami Djurabi R, Nijkeuter M,Alternative diagnosis other than pulmonary embolism as a subjective variable in the Wells clinical decision rule: not so bad after all[J]. J Thromb Haemost, 2007, 5(5): 1079?1080.

[11] Parent F, Ma?tre S, Meyer G,. Diagnostic value of D-dimer in patients with suspected pulmonary embolism: results from a multicentre outcome study[J]. Thromb Res, 2007, 120(2): 195?200.

[12] Wang Y, Liu ZH, Zhang HL,. Predictive value of D-dimer test for recurrent venous thromboembolism at hospital discharge in patients with acute pulmonary embolism[J]. J Thromb Thrombolysis, 2011, 32(4): 410?416.

[13] Carrier M, Righini M, Djurabi RK,. VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies[J]. Thromb Haemost, 2009, 101(5): 886?892.

[14] Pasha SM, Klok FA, Snoep JD,Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis[J]. Thromb Res, 2010, 125(4): e123?e127.

[15] Klok FA, Kruisman E, Spaan J,. Comparison of the revised Geneva score with the Wells rule for assessing clinical probability of pulmonary embolism[J]. Thromb Haemost, 2008, 6(1): 40?44.

[16] Douma RA, Mos IC, Erkens PM,. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism[J]. Ann Intern Med, 2011, 154(11): 709?718.

（編輯: 周宇紅）

Diagnostic value of revised Geneva score combined with plasma level of D-dimer for suspected pulmonary embolism in elderly patients

HU Jing-Min, ZHAO Can, GUO Dan-Jie*

(Heart Center, People’s Hospital, Peking University, Beijing 100044, China)

To evaluate the clinical diagnostic and exclusive values of revised Geneva score and its combination with plasma level of D-dimer for suspected pulmonary embolism (PE) in the elderly patients.A total of 276 patients with suspected PE due to chest pain and dyspnea admitted in our hospital from January 2009 to April 2014 were enrolled in this study. They were divided into 2 groups based on their age, that is, the aged group (≥60 years old) and the non-aged group (＜60 years old). Computed tomography pulmonary arteriography (CTPA) was considered as the gold standard for diagnosis. According to the revised Geneva score, the diagnosis of PE was categoried into different clinical probability,low, medium and high probability, and their plasma level of D-dimer was also tested. Based on their clinical features, the diagnostic values of revised Geneva score, the exclusive values of plasma D-dimer, and that of combining revised Geneva score with D-dimer together were analyzed between the 2 groups. The receiver operating characteristics (ROC) curve was used to evaluate the overall accuracy of revised Geneva score in the diagnosis of PE.Among the cohort with suspected PE, 80 cases were definitely diagnosed as PE by CTPA (52 cases ≥60 years old, and 28 cases ＜60 years old). The area under the ROC curve (AUC) was 0.974 (95% CI: 0.940?0.992) for the aged group and 0.981 (95% CI: 0.924?0.998）for the non-aged one, with significant difference between them (＜0.001). The negative predictive values of D-dimer, and the revised Geneva score combined with D-dimer were 93.8% and 100.0% respectively for the aged patients, and 88.9% and 100.0% for the non-aged patients.The clinical features of PE are atypical in the elderly patients. The revised Geneva score has lower diagnostic value for the aged than the non-aged patients. Combination of revised Geneva score and plasma level of D-dimer is a safe strategy to rule out PE and is better than D-dimer alone for the aged and non-aged patients with suspected PE.

elderly; pulmonary embolism; revised Geneva score; plasma D-dimer

R543.2; R592

A

10.11915/j.issn.1671-5403.2015.04.066

2015?01?07;

2015?02?05

郭丹杰, E-mail: guodanjie@pkuph.edu.cn