DISORDERED HEMOSTASIS IN EXTRAHEPATIC PORTAL-HYPERTENSION

To assess the contribution of naturally occurring portal-systemic shun ts to the coagulopathy of patients with liver disease, we studied labo ratory parameters of hemostasis in 20 adult patients with extrahepatic portal hypertension, secondary to portal vein thrombosis, that had re sulted in variceal bleeding. All extrahepatic portal hypertension pati ents had normal liver function and histological appearance. None had a ny evidence of preexisting coagulation disorders, and none had bled or undergone sclerotherapy in the 6 mo before study. Age- and gender-mat ched groups of 20 healthy individuals and 20 stable patients with cirr hosis and portal hypertension who had a history of variceal bleeding s erved as controls. Both patient groups had thrombocytopenia consistent with hypersplenism and portal hypertension. Prothrombin international normalized ratio (extrahepatic portal hypertension, 1.3 +/- 0.12; cir rhosis, 1.7 +/- 0.2; control, 1.02 +/0. 06; p < 0.05) and partial thro mboplastin time ratios (extrahepatic portal hypertension, 1.12 +/- 0.1 ; cirrhosis, 1.26 +/- 0.2; controls, 1.01 +/- 0.03; p < 0.05) were sig nificantly prolonged in both patient groups. Extrahepatic portal hyper tension and cirrhotic patient groups had significantly increased level s of serum total fibrin(ogen)-related antigen (extrahepatic portal hyp ertension, 818 +/- 150 ng/ml; cirrhosis, 454 +/- 52 ng/ml; controls, 1 24 +/- 7.3 ng/ml; p < 0.05), fibrin monomer (extrahepatic portal hyper tension, 168.8 +/- 16.9 ng/ml; cirrhosis, 115.6 +/- 11.1 ng/ml; contro ls, 19.7 +/- 0.4 ng/ml; p < 0.05) and D-dimer (extrahepatic portal hyp ertension, 118 +/- 9.6 ng/ml; cirrhosis, 129 +/- 10 ng/ml; controls, 5 3.2 +/- 1.6 ng/ml; p < 0.05). Extrahepatic portal hypertension patient s had higher total fibrinogen levels (4.15 +/- 1.4 gm/L) than did cont rols (3.35 +/- 0.21 gm/L; p < 0.05). Patients with extrahepatic portal hypertension (tissue plasminogen activator, 22.1 +/- 7; plasminogen a ctivator inhibitor type 1, 51 +/- 26) and cirrhosis (tissue plasminoge n activator, 23.8 +/- 15; plasminogen activator inhibitor type 1, 65 /- 30) had significantly higher concentrations of circulating tissue p lasminogen activator and plasminogen activator inhibitor type I than d id controls (tissue plasminogen activator, 5.8 +/- 1.1 ng/ml; plasmino gen activator inhibitor type 1, 5.2 +/- 1.8 ng/ml; p < 0.05 for both c omparisons). Analysis of specific coagulation factors revealed reduced levels of factors V, VII and IX, with increases of factor VIII levels in both patient groups suggestive of compensated mild, disseminated i ntravascular coagulation. Our data suggest that portal systemic shunti ng alters parameters of hemostasis, even in the apparent absence of li ver disease, and raise the possibility that such shunting is responsib le, at least in part, for the disordered coagulation and fibrinolysis seen in patients with chronic liver disease.