Coagulation abnormalities induced by
pancreatitis were studied in 36 dogs. The 12 dogs in group I underwent a duodenotomy alone. The six dogs in groups II, III, IV, and V had
pancreatitis induced by bile injection (1 cc/kg) into the pancreatic duct. Twenty minutes after bile-induced
pancreatitis, group III was given 1.0 mg/kg
aprotinin (
trasylol), group IV was given 10 mg/kg
S-2441, a new synthetic
protease inhibitor, and group V was given 0.5 mg/kg alpha 2-antitrypsin by
intravenous infusion over 10 min. Blood was drawn for
amylase, protime (PT), partial thromboplastin time (PTT),
fibrinogen, and platelets, in addition to markers of hypercoagulation,
fibrinopeptide A, and
antithrombin III, and markers of fibrinolysis, B beta 15-42 immunoreactive
peptide (IP), and alpha 2-antiplasmin at baseline, 1/2, 1, 3, 6, 24, 48, and 72 hr after duodenotomy or bile injection. There was no significant difference in PT, platelets,
antithrombin III, and
fibrinopeptide A among the five groups. With the induction of
pancreatitis (group II), serum
amylase was significantly elevated but
fibrinogen only became elevated at 24 hr and PTT at 48 hr. The increase in B beta 15-42 IP seen 30 min after induction of
pancreatitis and the decrease in alpha 2-antiplasmin were blunted by
aprotinin,
alpha 1-antitrypsin, and
S-2441, but inhibition of the rise in
amylase and B beta 15-42 IP only reached significance with
S-2441 (P less than 0.05).
Pancreatitis-induced fibrinolysis was inhibited by
S-2441 suggesting that synthetic
protease inhibitors may play a therapeutic role in
pancreatitis.