title: High coagulation factor levels and low protein C levels contribute to enhanced thrombin generation in patients with diabetes who do not have macrovascular complications.
abstract: OBJECTIVE
  A prothrombotic state characterized by activation of the coagulation system has been implicated in the pathogenesis of vascular complications in diabetes mellitus. Recently, a thrombin generation assay was introduced as a laboratory assessment of global hemostatic potential. We used this thrombin generation assay to investigate global hemostatic potential in patients with diabetes who did not have macrovascular complications.
  
  
  METHODS
  This study was a prospective case-control study comparing 89 patients with diabetes with 49 healthy controls. The thrombin generation assay was conducted with the calibrated automated thrombogram using tissue factor with or without the addition of thrombomodulin, giving values for lag time, endogenous thrombin potential, and peak thrombin.
  
  
  RESULTS
  Patients with diabetes showed hypercoagulability, as detected by the thrombin generation assay, compared with healthy controls. Correspondingly, high levels of coagulation factors (II, V, VII, VIII, and X) and low levels of anticoagulant (protein C) were major contributing factors in this hypercoagulability. Interestingly, a high blood glucose level was correlated with shortened clotting time, reflecting the association between hyperglycemia and hypercoagulability. Patients who were taking statins or angiotensin receptor blockers showed decreased endogenous thrombin potential ratio and increased protein C levels, suggesting relative hypocoagulability.
  
  
  CONCLUSIONS
  Patients with diabetes showed hypercoagulability, high levels of coagulation factors, and low levels of protein C. Further study is required to investigate how this hemostatic potential may be used to guide physicians toward more effective management of hemostatic complications.
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Il Sung
authors.initials: IS
authors.lastname: Nam-Goong
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea. Electronic address: endo10@daum.net.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D019851:Thrombophilia / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D001786:Blood Glucose; D011486:Protein C; D013917:Thrombin
keywords: Angiotensin receptor blocker; Coagulation factors; Patients with diabetes; Statins; Thrombin generation assay