Usefulness of Early Diagnosis of Sepsis-Induced Coagulopathy by Measuring Novel Platelet Activation Marker Soluble Type C Lectin-Like Receptor 2 (CLEC-2)

Abstract

\n Background: 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, such as cerebral or myocardial infarction. In the present study, we examined the relationship between sCLEC-2 level and degree of coagulation disorder, especially platelet activation, in sepsis patients. Methods: Seventy sepsis patients were enrolled and divided into two groups, sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n=44) and non-SID group (n=26), at the time of intensive care unit admission. In addition, 37 healthy adult volunteers were enrolled as a control group. The sCLEC-2 levels were measured and compared among the groups. Because we suspected that the sCLEC-2 level was likely to be affected by the platelet count, we also calculated the sCLEC-2/platelet count ratio (termed C2PAC index) in the groups. We further divided the sepsis patients into four groups using the Japanese Acute Medical Association (JAAM) DIC scoring system (DIC scores: 0–1, 2–3, 4–5, 6–8) and investigated the C2PAC indexes in the healthy volunteers and the four JAAM DIC score groups. Finally, we examined whether the C2PAC index could be a predictor of DIC by receiver-operating curve (ROC) analysis.Results: The C2PAC indexes in the healthy volunteers, non-SID group, and SID group were 0.34±0.14, 1.2±0.5, and 2.6±1.7, respectively. The index was significantly higher in the non-SID and SID groups compared with the healthy volunteers and also significantly higher in the SID group compared with the non-SID group (all P<0.001). The C2PAC indexes in the healthy volunteers and the four JAAM DIC score groups were 0.3±0.1, 0.9±0.3, 1.1±0.3, 1.7±0.7, and 3.6±1.0, respectively. Furthermore, the C2PAC index increased significantly as the DIC score increased (P<0.001). According to the ROC analysis, the area under the curve and optimal cut-off value for the diagnosis of DIC were 0.80507 and 1.40 (sensitivity, 75.0%; specificity, 76.9%), respectively.Conclusions: The present findings suggest that evaluation of the C2PAC index may be a useful early predictor of sepsis-induced coagulopathy progression and DIC diagnosis in sepsis patients.Trial registration: This study was approved by the institutional ethics committees at Fukuoka University Hospital (U19-01-001), Yamanashi University Hospital (2289), and LSI Medience Corporation (Shindan/Narita 19-04).