Behaviour of Protein C Inhibitor in Intravascular Coagulation and Liver Disease

Summary

We measured levels of protein C inhibitor in patients with disseminated intravascular coagulation (DIC) and liver disease using a functional assay. Levels in 24 normal subjects averaged 93% of the amount in normal pooled plasma, giving a normal range of 65 to 121%. Levels were below normal in 8 of 17 patients with DIC, in 4 of 19 patients with liver cirrhosis, and in 3 patients with acute hepatic necrosis. Levels were normal or elevated in 9 of 10 patients with cirrhosis and accelerated fibrinolysis, and in 6 patients receiving warfarin. We conclude that protein C inhibitor may be involved in regulation of protein C activity during pathologic activation of the hemostatic system (DIC). Decreased protein C inhibitor does not appear to contribute to the pathogenesis of accelerated fibrinolysis in liver disease. The liver may be the site of synthesis of protein C inhibitor.

Keywords

Protein C - Protein C inhibitor - Disseminated intravascular coagulation - Liver disease

• References

• 1 Walker FW, Sexton PW, Esmon CT. The inhibition of blood coagulation by activated protein C through the selective inactivation of activated factor V. Biochim Biophys Acta 1979; 571: 333-342
• 2 Vehar GA, Davie EW. Preparation and properties of bovine factor VIII. Biochemistry 1980; 19: 401-410
• 3 Comp PC, Esmon CT. Generation of fibrinolytic activity by infusion of activated protein C into dogs. J Clin Invest 1981; 68: 1221-1228
• 4 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-1376
• 5 Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families N Engl J Med 1983; 309: 340-344
• 6 Griffin JH, Mosher DF, Zimmerman TS, Kleiss AJ. Protein C, an antithrombotic protein, is reduced in hospitalized patients with intravascular coagulation. Blood 1982; 60: 261-264
• 7 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; 2: 463-467
• 8 Esmon NL, Owen WG, Esmon CT. Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 1982; 257: 859-864
• 9 Walker FJ. Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation J Biol Chem 1981; 256: 11128-11131
• 10 Suzuki K, Nishioka J, Hashimoto S. Protein C inhibitor. Purification from human plasma and characterization J Biol Chem 1983; 258: 163-168
• 11 Marlar RA, Griffin JH. Deficiency of protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest 1980; 66: 1186-1189
• 12 Canfield WM, Kisiel W. Evidence of normal functional levels of activated protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest 1982; 70: 1260-1272
• 13 Suzuki K, Nishioka J, Hashimoto S, Kamiya T, Saito H. Normal titer of functional and immunoreactive protein-C inhibitor in plasma of patients with congenital combined deficiency of factor V and factor VIII. Blood 1983; 62: 1266-1270
• 14 Hjort P, Rapaport SI, Owren PA. A simple, specific one-stage prothrombin assay using Russells’s viper venom in cephalin suspension. J Lab Clin Med 1955; 46: 89-97
• 15 Owren PA, Aas K. The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin. Scand J Clin Lab Invest 1951; 3: 201-208
• 16 Gallimore MJ, Shaw JT B. The influence of various plasma components on the lysis of dilute human blood clots. Thrombos Diathes Haemorrh 1969; 22: 223-233
• 17 Stormorken H. The preparation of proaccerlerin deficient (parahemophilia) plasma for the assay of proaccelerin. Scand J Clin Lab Invest 1957; 9: 273-276
• 18 Schiffman S, Rapaport SI, Patch MJ. Starch block electrophoresis of plasma and serum clotting factors. Separation of activated PTC (PTC’) Blood 1965; 25: 724-735
• 19 Francis Jr RB, Patch MJ. A functional assay for protein C in human plasma. Thromb Res 1983; 32: 605-613
• 20 Kisiel W. Human plasma protein C. Isolation, characterization, and mechanism of activation by alpha-thrombin J Clin Invest 1979; 64: 761-769
• 21 Rake MO, Flute PT, Pannell G, Williams R. Intravascular coagulation in acute hepatic necrosis. Lancet 1970; 1: 533-537
• 22 Comp PC, Jacocks RM, Rubenstein C, Radcliffe R. A lysine- adsorbable plasminogen activator is elevated in conditions associated with increased fibrinolytic activity. J Lab Clin Med 1981; 97: 637-645