Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus

Am J Hematol. 1997 Oct;56(2):93-9. doi: 10.1002/(sici)1096-8652(199710)56:2<93::aid-ajh4>;2-w.


Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbuminuria). A cross-sectional study of lipid profile, coagulation parameters, and a flow-cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re-evaluated for microangiopathy in a 3-year median follow-up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D-dimer (P < 0.00001), prothrombin fragment 1 + 2 (P < 0.00001), and thrombin-antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangiopathy in the follow-up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Diabetes Mellitus, Type 1 / blood
  • Diabetic Angiopathies / metabolism*
  • Female
  • Follow-Up Studies
  • Hemostasis
  • Humans
  • Lipids / blood
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Prospective Studies
  • Thrombomodulin / blood*
  • Thromboplastin / metabolism*


  • Biomarkers
  • Lipids
  • Lipoproteins
  • Thrombomodulin
  • Thromboplastin