Errors in the diagnosis for DIC due to a statistical misunderstanding

Abstract

Hemorrhaging is the most important source of maternal morbidity and mortality, and one of the main causes for life‐threatening obstetrical bleeding is disseminated intravascular coagulation (DIC).1.Collins P. Abdul‐Kadir R. Thachil J. Subcommittees on Women' s Health Issues in Thrombosis and Haemostasis and on Disseminated Intravascular CoagulationManagement of coagulopathy associated with postpartum hemorrhage: guidance from the SSC of the ISTH.J Thromb Haemost. 2016; 14: 205-210Crossref PubMed Scopus (81) Google Scholar Pregnant women have various hemostatic abnormalities, such as elevated fibrin‐related products (FRPs) and fibrinogen and a shortened prothrombin time (PT) and activated partial thromboplastin time (APTT). In addition, the clinical course of DIC in obstetrics is rapid and requires prompt treatment. While the definition and diagnosis of DIC in obstetrics remain unclear, the International Society on Thrombosis and Haemostasis (ISTH) has established a definition and diagnostic criteria for overt DIC.2.Taylor Jr, F.B. Toh C.H. Hoots K. Wada H. Levi M. Towards a definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation.Thromb Haemost. 2001; 86: 1327-1330Crossref PubMed Scopus (1539) Google Scholar We are very interested in the report3.Rabinovich A. Abdul‐Kadir R. Thachil J. Iba T. Othman M. Erez O. DIC in obstetrics: Diagnostic score, highlights in management, and international registry‐communication from the DIC and Women's Health SSCs of the International Society of Thrombosis and Haemostasis.J Thromb Haemost. 2019; 17: 1562-1566Crossref PubMed Scopus (18) Google Scholar from Rabinovich et al discussing the pregnancy‐modified ISTH DIC score and calling for an international registry for DIC in obstetrics. Although this registry will undoubtedly be important, no registry criteria have yet been established. There are marked differences between the pregnancy‐modified ISTH DIC score and ISTH overt DIC score. The pregnancy‐modified ISTH DIC score was established by Erez et al4.Erez O. Novack L. Beer‐Weisel R. et al.DIC score in pregnant women–a population based modification of the International Society on Thrombosis and Hemostasis score.PLoS One. 2014; 9Crossref Scopus (59) Google Scholar based on a receiver operating characteristics (ROC) curve analysis. The cutoff value by ROC analysis may cause a high sensitivity but a low specificity for DIC, which thus results in an overdiagnosis due to a statistical misunderstanding. A pregnant woman with a PT of 12.6 seconds (normal value 11.0 seconds) and fibrinogen 2.9 g/L will be diagnosed with DIC by the pregnancy‐modified ISTH DIC score (50 points). In our hospital, a PT difference >1.5 seconds and fibrinogen <3.0 g/L were observed at delivery in 4.1% and 14.3% of patients, respectively. These findings suggest that an overdiagnosis of DIC may be caused by the use of the pregnancy‐modified ISTH DIC score. ISTH overt DIC also has issues associated with FRPs. If D‐dimer levels >0.5 and >2 μg/mL are evaluated as 2 and 3 points, respectively, using the ISTH overt DIC score may result in the overdiagnosis.5.Suzuki K. Wada H. Imai H. et al.A re‐evaluation of the D‐dimer cut‐off value for making a diagnosis according to the ISTH overt‐DIC diagnostic criteria: communication from the SSC of the ISTH.J Thromb Haemost. 2018; 16: 1442-1444Crossref PubMed Scopus (34) Google Scholar The diagnostic criteria for DIC established by the Japanese Association for Acute Medicine (JAA) are also based on statistical analyses, and are high sensitive but low specific for DIC. We hope that this registry study will be useful for revising the pregnancy‐modified ISTH DIC score. There are no conflicts of interest associated with this study. HW wrote the manuscript, and KS and MS discussed and revised the manuscript. This work was supported in part by a Grant‐in‐Aid from the Ministry of Health, Labour and Welfare of Japan.Grant‐in‐Aid from the Ministry of Health, Labour and Welfare of Japan