活化部分凝血活酶时间延长混合血浆纠正试验“灰区”解决方案探究

Explore solutions to the"grey zone"of activated partial thromboplastin time mixing study

目的探索解决APTT纠正试验Rosener指数"灰区"的方法,建立APTT纠正试验结果判断的临床应用路径。方法收录2018年1月1日至2019年12月31日就诊于四川大学华西医院的APTT单独延长的患者样本,借助ROC曲线探索不同方案的最佳判断界值,建立联合应用1∶1和4∶1混合解决"灰区"问题的方案和结果判断的临床应用路径;收录2020年1月1日至12月31日的同类样本验证该方案和路径的诊断效能。结果传统Rosener指数判断标准对因子缺乏和抑制物的区分效能较低,建立组和验证组共49例(15%)样本位于"灰区";建立1∶1混合纠正试验Rosner指数判断因子缺乏的最佳界值为5.0%,判断抑制物的最佳界值为9.1%,对于5.0%~9.1%的样本进行4∶1混合纠正试验能明显提高低滴度抑制物的检出率;借鉴Rosner指数建立孵育后延长时间百分比-P(1∶1混合时>10.8%和4∶1混合时>13.5%)用于判断抑制物具有时间依赖性较共识推荐的2种方案诊断效能更高。联合1∶1和4∶1混合纠正试验对于因子缺乏和抑制物判断的敏感度、特异度、阳性预测值和阴性预测值均>90%,将抑制物误判为因子缺乏的比例从20.9%(9/43)下降到7.0%(3/43),将判断时间依赖性抑制物的特异性由54.2%提高至100%,准确度由63.3%提高至97.4%。结论1∶1和4∶1混合纠正试验联合应用可较好地解决"灰区"问题,建立的APTT纠正试验结果判断路径,有助于APTT纠正试验的进一步推广和临床应用。

Objective:To explore solutions to the "grey zone" of activated partial thromboplastin time (APTT) mixing study, and establish the clinical application pathway of it.Methods:Patients treated in West China Hospital of Sichuan University from January 1, 2018, to December 31, 2019, with a prolonged APTT were included in this study. The ROC curve was used to analyze the"cut-off"of different methods and explore solutions to the "grey zone" by combination of the 1∶1 and 4∶1 mixing study. Similar samples from January 1, 2020 to December 31, 2020 were included to verify the diagnostic efficiency of the clinical application pathway.Results:The traditional Rosner index criterion had a low diagnostic accuracy in differentiating factor deficiencies from inhibitors. A total of 49 cases (15%) in the establishment group and validation group were located in the "grey zone". The optimal cut-off value of the Rosner index in our 1∶1 mixing study for determining factor deficiency was 5.0%, and inhibitor was 9.1%. The sample between 5.0% and 9.0% needed 4∶1 mixing studies, which could significantly improve the detection sensitivity of inhibitors. The percentage of extended time after incubation-P (1∶1 mixing>10.8% and 4∶1 mixing>13.5%) was better than the traditional criterion mentioned by"consensus"in determining whether the inhibitor was time-dependent. The sensitivity, specificity, positive predictive value and negative predictive value of combined the 1∶1 and 4∶1 mixing study in differentiating factor deficiencies from inhibitors all attained more than 90%. Only 7% (3/43)of inhibitors were incorrectly classified into the factor deficiency group by the combination, which was 20.9% (9/43) by traditional criterion. The specificity for detecting time-dependent inhibitor was increased from 54.2% to 100%, and accuracy was increased from 63.3% to 97.4%.Conclusions:The combination of 1∶1 and 4∶1 mixing study can better resolve the "grey zone". The established clinical application pathway is beneficial for the further promotion and clinical application of APTT mixing study.