Early recognition of sepsis-induced coagulopathy using the C2PAC index: a ratio of soluble type C lectin-like receptor 2 (sCLEC-2) level and platelet count

Abstract

C-type lectin-like receptor 2 (CLEC-2) is a platelet-activated receptor expressed on the surface of platelet membranes. Soluble CLEC-2 (sCLEC-2) has been receiving attention as a predictive marker for thrombotic predisposition. The present study examined the relationship between sCLEC-2 level and degree of coagulation disorder in septic patients. Seventy septic patients were divided into the sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n = 44) and non-SID group (n = 26). The sCLEC-2 levels were compared between the two groups. Because we suspected that the sCLEC-2 level was affected by the platelet count, we calculated the sCLEC-2/platelet count ratio (C2PAC index). We further divided septic patients into four groups using the Japanese Association for Acute Medicine (JAAM) DIC scoring system (DIC scores: 0–1, 2–3, 4–5, and 6–8). The C2PAC index was significantly higher in the SID group (2.6 ± 1.7) compared with the non-SID group (1.2 ± 0.5) (P < .001). The C2PAC indexes in the four JAAM DIC score groups were 0.9 ± 0.3, 1.1 ± 0.3, 1.7 ± 0.7, and 3.6 ± 1.0, respectively, and this index increased significantly as the DIC score increased (P < .001). According to the receiver-operating curve analysis, the area under the curve (AUC) and optimal cutoff value for the diagnosis of SID were 0.8051 and 1.4 (sensitivity, 75.0%; specificity, 76.9%), respectively. When the C2PAC index and D-dimer level, one of the main fibrinolytic markers, were selected as predictive markers for SID diagnosis in stepwise multiple logistic regression analysis, it was possible to diagnose SID with a high probability (AUC, 0.9528; sensitivity, 0.9545; specificity, 0.8846). The C2PAC index is a useful predictor of SID progression and diagnosis in septic patients.

Keywords:

• C-type lectin-like receptor 2 (CLEC-2)
• disseminated intravascular coagulation (DIC)
• platelet activation
• sepsis
• sepsis-induced coagulopathy (SIC)

Acknowledgements

The authors thank Kelly Zammit, BVSc, and Alison Sherwin, PhD, from Edanz Group (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Ethics approval and consent to participate

The following ethics review boards approved the protocol for this study: Fukuoka University Hospital (U19-01-001; registered on 19 January 2019); Yamanashi University Hospital (2289; registered on 17 June 2020); LSI Medience Corporation (Shindan/Narita 19-04; registered on 19 May 2019).

Consent for publication

We obtained written informed consent for the publication of this study from all patients or their proxy in accordance with the Declaration of Helsinki. Copies of the informed consent documents are available from the corresponding author on reasonable request.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

MK is an employee of LSI Medience Corporation. The other authors declare that they have n competing interests.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Authors’ contributions

Hiroyasu Ishikura contributed to the study design, statistical analysis, interpretation of the results, drafting of the manuscript, and critical revision of the manuscript for intellectual content. Yuhei Irie and Masahide Kawamura participated in the study design, statistical analysis, and interpretation of the results. Masahide Kawamura is also an employee of LSI Medience Corporation. Kota Hoshino and Yoshihiko Nakamura were involved in data acquisition and performed the statistical analysis. Mariko Mizunuma, Junichi Maruyama and Maiko Nakashio were involved in data acquisition. Katsue Suzuki-Inoue carried out the ELISA assays and participated in the development and methodology. Taisuke Kitamura helped to draft the manuscript. All authors have read and approved the final manuscript.

Authors’ information

Hiroyasu Ishikura is a member of the Scientific Standardization Committee (SSC) for disseminated intravascular coagulation (DIC) of the Japanese Society for Thrombosis and Hemostasis (JSTH).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.