Abstract
IntroductionThrombomodulin, which is expressed solely on monocytes, along with tissue factor (TF), takes part in coagulation and inflammation. Circulating blood monocytes can be divided into 3 major subtypes on the basis of their receptor phenotype: classical (CD14brightCD16negative, CMs), inflammatory (CD14brightCD16positive; IMs), and dendritic cell-like (CD14dimCD16positive DMs). Monocyte subtype is strongly regulated, and the balance may influence the clinical outcomes of disseminated intravascular coagulation (DIC). Therefore, we investigated the phenotypic difference in thrombomodulin and TF expression between different monocyte subtypes in coagulopathy severity and prognosis in patients suspected of having DIC.MethodsIn total, 98 patients suspected of having DIC were enrolled. The subtypes of circulating monocytes were identified using CD14 and CD16 and the thrombomodulin and TF expression in each subtype, expressed as mean fluorescence intensity, was measured by flow cytometry. Plasma level of tissue factor was measured by ELISA. In cultures of microbead-selected, CD14-positive peripheral monocytes, lipopolysaccharide (LPS)- or interleukin-10-induced expression profiles were analyzed, using flow cytometry.ResultsThe proportion of monocyte subtypes did not significantly differ between the overt and non-overt DIC groups. The IM thrombomodulin expression level was prominent in the overt DIC group and was well correlated with other coagulation markers. Of note, IM thrombomodulin expression was found to be an independent prognostic marker in multivariate Cox regression analysis. In addition, in vitro culture of peripheral monocytes showed that LPS stimulation upregulated thrombomodulin expression and TF expression in distinct populations of monocytes.ConclusionsThese findings suggest that the IM thrombomodulin phenotype is a potential independent prognostic marker for DIC, and that thrombomodulin-induced upregulation of monocytes is a vestige of the physiological defense mechanism against hypercoagulopathy.
Highlights
Thrombomodulin, which is expressed solely on monocytes, along with tissue factor (TF), takes part in coagulation and inflammation
These findings suggest that the inflammatory monocyte (IM) thrombomodulin phenotype is a potential independent prognostic marker for disseminated intravascular coagulation (DIC), and that thrombomodulin-induced upregulation of monocytes is a vestige of the physiological defense mechanism against hypercoagulopathy
Levels than non-overt DIC patients, and prothrombin time, D-dimer level, Sequential Organ Failure Assessment (SOFA) score, Simplified Acute Physiology Score II (SAPS II), and plasma TF level were significantly higher in the overt DIC patients
Summary
Thrombomodulin, which is expressed solely on monocytes, along with tissue factor (TF), takes part in coagulation and inflammation. Activated protein C inactivates factors Va and VIIIa and inhibits further thrombin generation and plays an important role in the anticoagulant state of the Disseminated intravascular coagulation (DIC) is characterized by systemic fibrin formation, resulting from increased generation of thrombin, simultaneous suppression of physiological anticoagulants, and impaired fibrinolysis [3]. A marked impairment in the protein C system worsens coagulopathy because the protein C pathway plays a role in the major regulatory loop that limits thrombin generation. This reduction in the protein C system is caused, in part, by the cytokine-induced decrement in TM activity and free protein S levels and impaired protein synthesis [3,4]. Because both inflammatory and antiinflammatory cytokines are usually elevated in DIC, these cytokines may affect the expression of TF and TM in monocytes
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