Disordered hemostasis in extrahepatic portal hypertension

Authors

  • Dr. Simon C. Robson,

    Corresponding author
    1. Department of Medicine, Medical Research Council Liver Research Centre, University of Cape Town, Cape Town, South Africa
    • Medical Research Council Liver Centre, Medical School, University of Cape Town, Observatory, 7925, South Africa
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  • Delawir Kahn,

    1. Department of Surgery, Medical Research Council Liver Research Centre, University of Cape Town, Cape Town, South Africa
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  • J. Kruskal,

    1. Department of Medicine, Medical Research Council Liver Research Centre, University of Cape Town, Cape Town, South Africa
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  • Arthur R. Bird,

    1. Department of Haematology, Medical Research Council Liver Research Centre, University of Cape Town, Cape Town, South Africa
    2. Western Province Blood Transfusion Service, Cape Town, South Africa
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  • Ralph E. Kirsch

    1. Department of Medicine, Medical Research Council Liver Research Centre, University of Cape Town, Cape Town, South Africa
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Abstract

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). Extrahepatic portal hypertension patients had higher total fibrinogen levels (4.15 ± 1.4 gm/L) than did controls (3.35 ± 0.21 gm/L; p < 0.05). Patients with extrahepatic portal hypertension (tissue plasminogen activator, 22.1 ± 7; plasminogen activator inhibitor type 1, 51 ± 26) and cirrhosis (tissue plasminogen activator, 23.8 ± 15; plasminogen activator inhibitor type 1, 65 ± 30) had significantly higher concentrations of circulating tissue plasminogen activator and plasminogen activator inhibitor type I than did controls (tissue plasminogen activator, 5.8 ± 1.1 ng/ml; plasminogen activator inhibitor type 1, 5.2 ± 1.8 ng/ml; p < 0.05 for both comparisons). 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 intravascular coagulation. Our data suggest that portal systemic shunting alters parameters of hemostasis, even in the apparent absence of liver disease, and raise the possibility that such shunting is responsible, at least in part, for the disordered coagulation and fibrinolysis seen in patients with chronic liver disease. (HEPATOLOGY 1993;18:853-857).

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