School of Health and Related Research, University of Sheffield, Sheffield, UK.
Guy's and St Thomas' NHS Foundation Trust, London, UK.
Health Technol Assess. 2018 Aug;22(47):1-230. doi: 10.3310/hta22470.
Pulmonary embolism (PE) is a leading cause of death in pregnancy and post partum, but the symptoms of PE are common in normal pregnancy. Simple diagnostic tests are needed to select women for diagnostic imaging.
To estimate the accuracy, effectiveness and cost-effectiveness of clinical features, decision rules and biomarkers for selecting pregnant or postpartum women with a suspected PE for imaging.
An expert consensus study to develop new clinical decision rules, a case-control study of women with a diagnosed PE or a suspected PE, a biomarker study of women with a suspected PE or diagnosed deep-vein thrombosis (DVT) and decision-analysis modelling.
Emergency departments and consultant-led maternity units.
Pregnant/postpartum women with a diagnosed PE from any hospital reporting to the UK Obstetric Surveillance System research platform and pregnant/postpartum women with a suspected PE or diagnosed DVT at 11 prospectively recruiting sites.
Clinical features, decision rules and biomarkers.
Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, quality-adjusted life-years (QALYs) and health-care costs.
The primary analysis involved 181 women with PE and 259 women without PE in the case-control study and 18 women with DVT, 18 with PE and 247 women without either in the biomarker study. Most clinical features showed no association with PE. The AUROC curves for the clinical decision rules were as follows: primary consensus, 0.626; sensitive consensus, 0.620; specific consensus, 0.589; PE rule-out criteria, 0.621; simplified Geneva score, 0.579; Wells's PE criteria (permissive), 0.577; and Wells's PE criteria (strict), 0.732. The sensitivities and specificities of the D-dimer measurement were 88.4% and 8.8%, respectively, using a standard threshold, and 69.8% and 32.8%, respectively, using a pregnancy-specific threshold. Previous venous thromboembolism, long-haul travel, multiple pregnancy, oxygen saturation, recent surgery, temperature and PE-related chest radiograph abnormality were predictors of PE on multivariable analysis. We were unable to derive a rule through multivariable analysis or recursive partitioning with adequate accuracy. The AUROC curves for the biomarkers were as follows: activated partial thromboplastin time - 0.669, B-type natriuretic peptide - 0.549, C-reactive protein - 0.542, Clauss fibrinogen - 0.589, enzyme-linked immunosorbent assay D-dimer - 0.668, Innovance D-dimer (Siemens Healthcare Diagnostics Products GmbH, distributed by Sysmex UK Ltd, Milton Keynes, UK) - 0.651, mid-regional pro-atrial natriuretic peptide (MRproANP) - 0.524, prothrombin fragment 1 + 2 - 0.562, plasmin-antiplasmin - 0.639, Prothombin time - 0.613, thrombin generation lag time - 0.702, thrombin generation endogenous potential - 0.559, thrombin generation peak - 0.596, thrombin generation time to peak - 0.655, tissue factor - 0.531 and troponin - 0.597. The repeat analysis excluding women who had received anticoagulation was limited by the small number of women with PE ( = 4). The health economic analysis showed that a strategy of scanning all women with a suspected PE accrued more QALYs and incurred fewer costs than any selective strategy based on a clinical decision rule and was therefore the dominant strategy.
The findings apply specifically to the diagnostic assessment of women with a suspected PE in secondary care.
Clinical features, decision rules and biomarkers do not accurately, effectively or cost-effectively select pregnant or postpartum women with a suspected PE for diagnostic imaging.
New diagnostic technologies need to be developed to detect PE in pregnancy.
Current Controlled Trials ISRCTN21245595.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 22, No. 47. See the NIHR Journals Library website for further project information.
肺栓塞（PE）是妊娠和产后死亡的主要原因，但 PE 的症状在正常妊娠中很常见。需要简单的诊断测试来选择需要进行影像学诊断的女性。
评估用于选择疑似 PE 的孕妇或产后女性进行影像学检查的临床特征、决策规则和生物标志物的准确性、有效性和成本效益。
一项旨在制定新的临床决策规则的专家共识研究、一项疑似 PE 或确诊 PE 女性的病例对照研究、一项疑似 PE 或确诊深静脉血栓形成（DVT）女性的生物标志物研究以及决策分析模型。
急诊室和顾问主导的产科病房。
来自英国产科监测系统研究平台报告的任何医院的确诊 PE 孕妇/产后女性和 11 个前瞻性招募点的疑似 PE 或确诊 DVT 孕妇/产后女性。
临床特征、决策规则和生物标志物。
敏感性、特异性、受试者工作特征曲线下面积（AUROC）、质量调整生命年（QALYs）和医疗保健成本。
主要分析涉及病例对照研究中的 181 名 PE 女性和 259 名非 PE 女性，以及生物标志物研究中的 18 名 DVT 女性、18 名 PE 女性和 247 名非 DVT/PE 女性。大多数临床特征与 PE 无关联。临床决策规则的 AUROC 曲线如下：主要共识，0.626；敏感共识，0.620；特异共识，0.589；PE 排除标准，0.621；简化日内瓦评分，0.579；Wells 的 PE 标准（宽松），0.577；和 Wells 的 PE 标准（严格），0.732。使用标准阈值时，D-二聚体检测的敏感性和特异性分别为 88.4%和 8.8%，使用妊娠特异性阈值时，敏感性和特异性分别为 69.8%和 32.8%。既往静脉血栓栓塞、长途旅行、多胎妊娠、氧饱和度、近期手术、体温和与 PE 相关的胸部 X 线异常是多变量分析中 PE 的预测因素。我们无法通过多变量分析或递归分区获得足够准确的规则。生物标志物的 AUROC 曲线如下：活化部分凝血活酶时间-0.669，B 型利钠肽-0.549，C 反应蛋白-0.542，Clauss 纤维蛋白原-0.589，酶联免疫吸附试验 D-二聚体-0.668，Innovance D-二聚体（Siemens Healthcare Diagnostics Products GmbH，由 Sysmex UK Ltd 分销，米尔顿凯恩斯，英国）-0.651，中区域前利尿钠肽（MRproANP）-0.524，凝血酶原片段 1+2-0.562，纤溶酶-抗纤溶酶-0.639，Prothombin 时间-0.613，凝血酶生成延迟时间-0.702，凝血酶生成内源性潜能-0.559，凝血酶生成峰-0.596，凝血酶生成时间到峰-0.655，组织因子-0.531 和肌钙蛋白-0.597。排除接受抗凝治疗的女性的重复分析受到疑似 PE 女性数量较少（n=4）的限制。健康经济学分析表明，与任何基于临床决策规则的选择性策略相比，对疑似 PE 的所有女性进行扫描的策略可获得更多的 QALYs 并减少成本，因此是主导策略。
研究结果专门适用于二级保健中疑似 PE 孕妇/产后女性的诊断评估。
临床特征、决策规则和生物标志物不能准确、有效或具有成本效益地选择疑似 PE 的孕妇或产后女性进行影像学检查。
需要开发新的诊断技术来检测妊娠中的 PE。
当前对照试验 ISRCTN21245595。
本项目由英国国家卫生研究所（NIHR）卫生技术评估计划资助，全文将在 ; 第 22 卷，第 47 期发表。有关该项目的更多信息，请访问 NIHR 期刊库网站。
