Decreased thrombomodulin mRNA expression on peripheral monocytes in disseminated intravascular coagulation patients relates to poor outcomes: The ex vivo effects of lipopolysaccharide and thrombin on monocyte thrombomodulin and CD14 mRNA

摘要

Background Monocytes express substantial amounts of thrombomodulin, which is consumed throughout ongoing thrombin generation. The modulation of thrombomodulin may aggravate intravascular fibrin deposition and the clinical course of disseminated intravascular coagulation (DIC). Although thrombomodulin restoration has received considerable attention, no reports have been published on the in vivo expression status of thrombomodulin. CD14 expression on monocytes is important for regulation of the inflammatory response. We used an ex vivo stimulation study to evaluate the association of the levels of monocyte-expressed thrombomodulin and CD14 messenger RNA (mRNA) with the severity and prognosis of disseminated intravascular coagulation. Methods A total of 78 patients with suspected DIC were enrolled. Thrombomodulin and CD14 mRNA levels were measured in peripheral blood by real-time quantitative reverse-transcription polymerase chain reaction. Thrombomodulin and CD14 mRNA were also assessed in ex vivo cultures of peripheral whole blood that were stimulated by lipopolysaccharide or thrombin. Results The levels of monocyte-expressed thrombomodulin mRNA were significantly lower in the non-survivors than in the survivors. A low level of monocyte-expressed thrombomodulin mRNA was a significant prognostic marker, but CD14 did not possess prognostic power. Monocyte-expressed CD14 mRNA correlated significantly with the severity of DIC in survivors. In addition, stimulation of ex vivo cultures of whole blood demonstrated that thrombin upregulates both thrombomodulin and CD14 mRNA, and lipopolysaccharide downregulates thrombomodulin mRNA. Conclusions The downregulation of thrombomodulin on monocytes reflects the decompensated status of physiological defenses against hypercoagulopathy and represents the poor prognosis in DIC. The expression levels of thrombomodulin on monocytes may be a useful marker to screen for candidates eligible for recombinant thrombomodulin therapy in future.