To assess the contribution of naturally occurring portal-systemic shunts to the coagulopathy of patients with liver disease, we studied laboratory parameters of hemostasis in 20 adult patients with extrahepatic portal hypertension, secondary to portal vein thrombosis, that had resulted in variceal bleeding. All extrahepatic portal hypertension patients had normal liver function and histological appearance. None had any evidence of preexisting coagulation disorders, and none had bled or undergone sclerotherapy in the 6 mo before study. Age- and gender-matched groups of 20 healthy individuals and 20 stable patients with cirrhosis and portal hypertension who had a history of variceal bleeding served as controls. Both patient groups had thrombocytopenia consistent with hypersplenism and portal hypertension. Prothrombin international normalized ratio (extrahepatic portal hypertension, 1.3 +/- 0.12; cirrhosis, 1.7 +/- 0.2; control, 1.02 +/- 0.06; p < 0.05) and partial thromboplastin time ratios (extrahepatic portal hypertension, 1.12 +/- 0.1; cirrhosis, 1.26 +/- 0.2; controls, 1.01 +/- 0.03; p < 0.05) were significantly prolonged in both patient groups. Extrahepatic portal hypertension and cirrhotic patient groups had significantly increased levels of serum total fibrin(ogen)-related antigen (extrahepatic portal hypertension, 818 +/- 150 ng/ml; cirrhosis, 454 +/- 52 ng/ml; controls, 124 +/- 7.3 ng/ml; p < 0.05), fibrin monomer (extrahepatic portal hypertension, 168.8 +/- 16.9 ng/ml; cirrhosis, 115.6 +/- 11.1 ng/ml; controls, 19.7 +/- 0.4 ng/ml; p < 0.05) and D-dimer (extrahepatic portal hypertension, 118 +/- 9.6 ng/ml; cirrhosis, 129 +/- 10 ng/ml; controls, 53.2 +/- 1.6 ng/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)