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DOI: 10.1055/s-0038-1646431
Low Levels of the Anticoagulant Activity of Protein C in Patients with Chronic Renal Insufficiency: an Inhibitor of Protein C Is Present in Uremic Plasma
Publikationsverlauf
Received 28. November 1990
Accepted 03. April 1991
Publikationsdatum:
25. Juli 2018 (online)
Summary
Twenty-nine of 54 uremic patients had low levels of protein C measured as anticoagulant activity, contrasting with normal levels measured as amidolytic activity or antigenic concentration. We demonstrate that this discrepancy is due to the presence of a soluble plasma inhibitor that interferes specifically with the anticoagulant activity of activated protein C. The inhibitor does not interfere with other coagulation assays. It is resistent to diisopropylfluorophosphate, high temperatures and repeated freezing and thawing. It can be dissociated from protein C by anti-protein C antibodies or by dialysis in vitro and in vivo. It binds to positively charged resins and can be eluted with high salt concentrations without losing its inhibitory capacity. The inhibitory effect is correlated with plasma creatinine levels and fluctuates with time.
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References
- 1 Esmon CT. Protein CV: biochemistry, physiology and clinical implications. Blood 1984; 63: 15-7
- 2 Clouse LH, Comp P. The regulation of hemostasis: the protein C system. N Engl J Med 1986; 314: 1298-304
- 3 Sorensen PJ, Knudsen F, Nielsen AH, Dyerberg J. Protein C activity in renal disease. Thromb Res 1985; 38: 243-9
- 4 Sorensen PJ, Knudsen F, Nielsen AH, Dyerberg J. Low protein C in hemodialysis patients. Blood Purification 1984; 2: 93-7
- 5 Sorensen PJ, Nielsen AH, Knudsen F, Dyerberg J. Defective protein C in uremia. Blood Purification 1987; 5: 29-32
- 6 Sorensen PJ, Knudsen F, Nielsen AH, Dyerberg J. Protein C assay in uremia. Thromb Res 1989; 54: 301-10
- 7 Francis RB. A simplified PTT-based protein C activity assay using the thrombin-thrombomodulin complex. Thromb Res 1986; 37: 337-44
- 8 Bertina RM, Broekmans AW, Kromenhoek-van Es, van Wijngaarden A. The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemostas 1984; 51: 1-5
- 9 Viganò-D'Angelo S, Comp P, Esmon CT, D'Angelo A. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest 1986; 77: 416-25
- 10 Franchi F, Tripodi A, Valsecchi C, Mannucci PM. Functional assay of protein C: comparison of two snake venom assays with two thrombin assays. Thromb Haemostas 1988; 60: 145-7
- 11 Laurell CB. Quantitative estimations of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 46-52
- 12 Mannucci PM, Viganò S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; 2: 463-6
- 13 Faioni EM, Esmon CT, Esmon NL, Mannucci PM. Isolation of an abnormal protein C molecule from the plasma of a patient with thrombotic diathesis. Blood 1988; 71: 940-6
- 14 Esmon NL, Owen WG, Esmon CT. Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 1982; 257: 859-64
- 15 Ingram GIC, Brozovic M, Slater NGP. Bleeding Disorders, Investigation and Management. Blackwell, Oxford: 1982
- 16 Mannucci PM, Boyer C, Tripodi A, Viganò-D'Angelo S, Wolf M, Valsecchi C, D'Angelo A, Meyer D, Larrieu MJ. Multicenter comparison of five functional and two immunological assays for protein C. Thromb Haemostas 1987; 57: 44-8
- 17 Brenner BM, Lazarus JM. Chronic renal failure: pathophysiologic and clinical considerations. In: Harrison's Principles of Internal Medicine.. Petersdorf RG, Raymond DA, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD. (eds) Mc Graw-Hill Book Company, New York: 1982. p 1613