title: Blood coagulation and fibrinolysis in patients with acromegaly: increased plasminogen activator inhibitor-1 (PAI-1), decreased tissue factor pathway inhibitor (TFPI), and an inverse correlation between growth hormone and TFPI.
abstract: OBJECTIVE
  Growth hormone/insulin-like growth factor-1(GH/IGF-1) hypersecretion may influence risk factors contributing to the increased cardiovascular morbidity and mortality associated with acromegaly However, so far little is known about the impact of GH/IGF-1 on coagulation and fibrinolysis in acromegalic patients as possible risk factors for cardiovascular disease (CVD). To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patients have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between GH/IGF-1 and these hemostatic parameters and serum lipid profile in patients with acromegaly.
  
  
  METHODS
  A total of 22 patients with active acromegaly and 22 age-matched healthy controls were included in the study. Fibrinogen, factors V, VII, VIII, IX, and X activities, von-Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-I (PAI-1), TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum GH/IGF-1 and these hemostatic parameters were evaluated.
  
  
  RESULTS
  Compared with the control subjects, fibrinogen, AT III, t-PA, and PAI-1 were increased significantly in patients with acromegaly (P < 0.0001, P < 0.05, P < 0.01, and P < 0.0001, respectively), whereas protein S activity and TFPI levels were decreased significantly (P < 0.05 and P < 0.01, respectively). Plasma TAFI Ag levels did not significantly change in patients with acromegaly compared with the controls. In patients with acromegaly, serum GH levels were inversely correlated with TFPI and apo AI levels (r: -0.514, P: 0.029 and r: -0.602, P: 0.014, respectively). There was also a negative correlation between insulin-like growth factor-1 (IGF-1) and PAI-1 (r: -0.455, P: 0.045).
  
  
  CONCLUSIONS
  We found some important differences in the hemostatic parameters between the patients with acromegaly and healthy controls. Increased fibrinogen, t-PA, PAI-1 and decreased protein S and TFPI in acromegalic patients may represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system and dyslipidemia may contribute to the excess mortality due to CVD seen in patients with acromegaly.
authors.affiliation: Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Karadeniz Technical University, Iç Hastaliklari Anabilim Dali, 61080 Trabzon, Turkey. cihangirerem@hotmail.com
authors.forename: Cihangir
authors.initials: C
authors.lastname: Erem
authors.forename: Irfan
authors.initials: I
authors.lastname: Nuhoglu
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kocak
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yilmaz
authors.forename: Safiye Tuba
authors.initials: ST
authors.lastname: Sipahi
authors.forename: Ozge
authors.initials: O
authors.lastname: Ucuncu
authors.forename: Halil Onder
authors.initials: HO
authors.lastname: Ersoz
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000453:epidemiology; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D050197:Atherosclerosis / Q000453:epidemiology; D001777:Blood Coagulation; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D015995:Prevalence; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology
chemical_list: D016632:Apolipoprotein A-I; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C051928:lipoprotein-associated coagulation inhibitor; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005340:Fibrinogen