Novel biomarkers for early prediction of sepsis-induced disseminated intravascular coagulation in a mouse cecal ligation and puncture model

Abstract

IntroductionThe objective of this study was to identify biomarkers of sepsis-induced disseminated intravascular coagulation (DIC) among platelet-derived factors using biotin label-based custom protein microarray technology in a mouse cecal ligation and puncture (CLP) model.MethodsKM mice were randomized into sham-operated and CLP groups. Blood samples were obtained immediately and at 1 h, 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after establishment of the CLP for platelet count, coagulation assay and blood chemistry. Lung and mesentery tissues were examined histologically at all corresponding time points, looking for microthrombus formation. Serial protein microarray analysis was performed to detect platelet-derived factors.ResultsThe survival rate 72 h post-CLP was 15%, but there was no mortality among the sham-operated mice. Compared with the sham group, the platelet count (n = 5, p < 0.05), fibrinogen concentration (n = 5, p < 0.05) and alanine aminotransferase level of the CLP group began to decrease significantly at 6 h post-CLP. Significant prolongation of prothrombin time (n = 5, p < 0.05) and activated partial thromboplastin time (n = 5, p < 0.05) and elevation of D-dimer (n = 5, p < 0.05) occurred after 6 h post-CLP. On histology, microthrombus formation in lung and mesentery tissue was observed in the CLP groups 6 h post-CLP and had become significant and extensive 12 h post-CLP (n = 5, p < 0.05). On protein microarray analysis and ELISA, thrombospondin (TSP), tissue inhibitor of metalloproteinase 1 (TIMP-1) and thymus chemokine-1 (TCK-1) all increased during the first 2 h post-CLP, then remained at a higher level than in the sham group for 72 h post-CLP (n = 5, p < 0.05).ConclusionsTSP, TIMP-1 and TCK-1 are elevated in the early stage of sepsis-induced DIC in a mouse CLP model and may be considered early markers for sepsis-induced DIC.

Salidroside rescued mice from experimental sepsis through anti-inflammatory and anti-apoptosis effects

“…The CLP model, by creating a bowel perforation with leakage of fecal material into the peritoneal cavity, is considered as closely resembling the course of sepsis observed in septic patients [22]. Our survival study demonstrated that the lethality of sepsis was markedly attenuated and delayed in septic mice administered with SDS probably due to the anti-inflammatory activity of SDS, which is consistent with the previous findings [23].…”

Toll‐like receptors 2 and 7 mediate coagulation activation and coagulopathy in murine sepsis

“…However, we only observed a clotting profile consistent with hypocoagulability. The increases in plasma TF and PAI‐1 levels and the concurrent decrease in the plasma ATIII level and elevated D‐dimer level suggest an activated coagulation process with reduction in clot quality (i.e., decreased MCF) and consumption of platelets …”

“…*P < 0.05. Ctrl, control; PE, phycoerythrin quality (i.e., decreased MCF) and consumption of platelets 34.…”

Coagulation Gene Expression Profiling in Infants With Necrotizing Enterocolitis

“…CD63 levels have recently been shown to be elevated in a mouse sepsisinduced DIC model. [27] A second possible biomarker related to the progression of the endothelial dysfunction is MFG-E8 (milk fat globule-EGF factor 8). It has been shown that, in septic mice, intestinal MFG-E8 expression is down-regulated leading to intestinal injury, impaired enterocyte migration and deficient mucosa regeneration.…”