Thrombin generation in vitro and in vivo, and disturbed tissue factor regulation in patients with acute pancreatitis.
BACKGROUND
Being a central link between inflammation and coagulation, tissue factor (TF) and its inhibitor (TFPI) might be associated with the severity of acute pancreatitis (AP) and the development of organ failure (OF).


METHODS
The study comprises 9 severe AP patients with OF and 24 reference patients (11 mild AP and 13 severe AP without OF). Plasma samples were collected on admission. TF-induced thrombin generation in plasma samples was studied using the thrombogram method. In vivo thrombin generation was estimated by prothrombin fragment F1+2. Free and total TFPI levels were measured. To evaluate coagulation status the activated partial thromboplastin time, prothrombin time, platelet count, D-dimer, fibrinogen, antithrombin (AT) 3 and protein C (PC) were determined.


RESULTS
There was no significant difference in F1+2 levels between the patient groups. Patients with severe AP tended to show low platelet counts, PC and AT3 levels, and high D-dimer levels. In 11 patients the standard TF stimulation did not trigger thrombin generation in the thrombogram. All deaths occurred in these patients. Free TFPI levels and free/total TFPI ratios were significantly higher in these patients and in non-survivors.


CONCLUSIONS
Failure of TF-initiated thrombin generation in the thrombogram assay explained by high levels of circulating free TFPI may be associated with OF and mortality in AP. and IAP.
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland. outi.lindstrom@hus.fi
Outi K
OK
Lindström
Eija M
EM
Tukiainen
Marja-Leena
ML
Kylänpää
Panu J
PJ
Mentula
Pauli A
PA
Puolakkainen
Ulla M K
UM
Wartiovaara-Kautto
Heikki
H
Repo
Jari M
JM
Petäjä
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D001780:Blood Coagulation Tests; D002478:Cells, Cultured; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D010195:Pancreatitis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D010976:Platelet Count; D015996:Survival Rate; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
D015415:Biomarkers; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D013917:Thrombin