title: Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex.
abstract: BACKGROUND
  Diurnal fluctuations of blood coagulation and fibrinolysis activity are thought to play a role in the observed circadian variation in the frequency of onset of acute cardiovascular events. In the present study, the diurnal variations in blood coagulation and fibrinolysis activity were investigated in 10 young, healthy control subjects by use of specific molecular activation markers.
  
  
  RESULTS
  The plasma levels of activated factor FVII (FVIIa), the active portion of the main coagulation activator, decreased during the day (8 AM: 2.03 ng/mL, CI 1.16 to 2.88 ng/mL; 8 PM: 1.16 ng/mL, CI 0.81 to 1.5 ng/mL; P = .005), whereas FVII antigen did not change significantly. In parallel with the diurnal variations of FVIIa, we found a decrease of prothrombin fragment F1+2 (8 AM: 0.97 nmol/L, CI 0.79 to 1.15 nmol/L; 8 PM: 0.78 nmol/L, CI 0.64 to 0.93 nmol/L; P = .005), a molecular marker of intravasal thrombin generation. Evidence for a possible functional relevance of circulating FVIIa was found because this parameter was significantly correlated with prothrombin fragment F1+2 in 72 fasting healthy individuals (r = .29, P = .011). Plasminogen activator inhibitor-1 levels decreased (8 AM: 9.9 ng/mL, CI 7.7 to 12.1 ng/mL; 8 PM: 5.4 ng/mL, CI 3.8 to 6.9 ng/mL; P < .005), whereas plasmin-plasmin inhibitor complex levels, representing the degree of intravascular plasmin generation, concomitantly increased (8 AM: 235 micrograms/L, CI 198 to 272 micrograms/L; 8 PM: 449 micrograms/L, CI 391 to 507 micrograms/L; P = .008).
  
  
  CONCLUSIONS
  Our data suggest that the diurnal changes in the plasma levels of activators and inhibitors of coagulation and fibrinolysis lead to corresponding changes in the activity state of these systems, leading to morning hypercoagulability and hypofibrinolysis.
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria. stylianos.kapiotis@univie.ac.at
authors.forename: S
authors.initials: S
authors.lastname: Kapiotis
authors.forename: B
authors.initials: B
authors.lastname: Jilma
authors.forename: P
authors.initials: P
authors.lastname: Quehenberger
authors.forename: K
authors.initials: K
authors.lastname: Ruzicka
authors.forename: S
authors.initials: S
authors.lastname: Handler
authors.forename: W
authors.initials: W
authors.lastname: Speiser
mesh_terms: D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents / Q000378:metabolism*; D001777:Blood Coagulation / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D002940:Circadian Rhythm / Q000502:physiology*; D003430:Cross-Sectional Studies; D005167:Factor VII / Q000032:analysis*; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis*; D012016:Reference Values; D014280:Triglycerides / Q000097:blood; D000979:alpha-2-Antiplasmin
chemical_list: D000933:Antifibrinolytic Agents; D010446:Peptide Fragments; D014280:Triglycerides; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; C045879:prothrombin fragment 1.2; D005167:Factor VII; D011516:Prothrombin; D002784:Cholesterol; D005341:Fibrinolysin