title: Thrombomodulin phenotype of a distinct monocyte subtype is an independent prognostic marker for disseminated intravascular coagulation.
abstract: BACKGROUND
  Thrombomodulin, 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, 101, Daehak-ro Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Hwang
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kyou-Sup
authors.initials: KS
authors.lastname: Han
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004211:Disseminated Intravascular Coagulation / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification* / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D018180:Thrombomodulin / Q000097:blood*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018180:Thrombomodulin; D013925:Thromboplastin