Diagnosis of Protein C Deficiency in Patients on Oral Anticoagulant Treatment: Comparison of Three Different Functional Protein C Assays

Summary

The efficacy of three different protein C activity assays and of protein C antigen determination for the diagnosis of protein C deficiency was studied in 13 protein C deficient patients (11 with type I, 2 with type II deficiency) and in 51 presumably nondeficient patients (control group), both groups being on oral anticoagulant (OAC) treatment. For protein C activity measurement (1) the assay according to Francis (slightly modified) with thrombin activation and measurement of activated protein C in the aPTT system, (2) an assay using Protac activation and chromogenic substrate (Protac-CS) and (3) an assay using Protac activation and the aPTT system (Protac-PTT) were used. Protein C antigen was determined by Laurcll immunoelec-trophoresis. The three activity assays gave different results, with the highest values obtained by the Protac-CS assay and the lowest values by the Protac-PTT assay. The Francis assay gave intermediate results.

Protein C activity and antigen values were significantly lower in protein C deficient patients compared to the control group. Protein C activity tests had a higher discriminative power than the antigen determination. After taking into account the intensity of treatment, by the Francis assay all deficient and non-deficient patients were correctly classified, by the Protac-CS and the Protac-PTT assay 2 and 4 patients, respectively, were misclas-sified and by the antigen assay 8 patients were misclassified. Calculation of the ratios of protein C activity to factor II activity was of high discriminative power.

We conclude that for diagnosis of protein C deficiency protein C activity tests are superior to antigen determination not only in type II but also in type I deficient patients. Certain statistical procedures can further improve the discrimination between deficient and non-deficient patients.

• References

• 1 Griffin JH, Evatt B, Zimmermann TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-3
• 2 Bertina RM, Broekmans AW, van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemostas 1982; 48: 1-5
• 3 Brockmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thromboembolism. A study in three Dutch families. N Engl J Med 1983; 309: 340-4
• 4 Pabinger-Fasching I, Bertin RM, Lechner K, Nicssner H, Korninger C. Protein C deficiency in two Austrian families. Thromb Haemostas 1983; 50: 810-3
• 5 Pabinger I. Clinical relevance of protein C. Blut 1986; 53: 63-75
• 6 Brockmans AW, Conard J. Hereditary protein C deficiency. In: Protein C and related proteins. Bertina RM. (ed) Churchill Livingstone; Edingburgh: 1988. pp 160-81
• 7 Bovill EG, Bauer KA, Dickerman JD, Callas P, West B. The clinical spectrum of heterozygous protein C deficiency in a large new England kindred. Blood 1989; 73: 712-7
• 8 Bertina RM, Broekmans AW, Krommenhock-van EsC. 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 Vigano D’Angelo S, Comp PC, 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 Comp PC, Nixon RR, Esmon CT. Determination of functional levels of protein C. an antithrombotic protein, using thrombin-throm-bomodulin complex. Blood 1984; 63: 15-21
• 11 Vigano S, Mannucci PM, Solinas S, Bottasso B, Mariani G. Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 1984; 57: 213-20
• 12 Pabinger I, Lechner K. Acquired protein C and protein S deficiency. In: Protein C and related proteins. Berina RM. (ed) Churchill Livingstone; 1988. pp 213-25
• 13 Francis RB, Patch MJ. A functional assay for protein C in human plasma. Thromb Res 1983; 32: 605-13
• 14 Francis RB, Seyfert U. Rapid amidolytic assay of protein C in whole plasma using an activator from the venom of agkistrodon contortrix. Am J Clin Pathol 1986; 87: 619-25
• 15 Martinoli JL, Stocker K. Fast functional protein C assay using Protac®, a novel protein C activator. Thromb Res 1986; 43: 253-64
• 16 Mannucci PM, Boyer C, Tripodi A, Vigano-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
• 1 Bertina RM. Report on the ICTH-protein C activity study. Unpublished 1986
• 18 Vukovich TC, Knöbl PN, Bauer K, Tragi KH, Deutsch E. Quantitative determination of human protein C. Evaluation of a “fast” functional assay in comparison to a “traditional” functional and an immunological assay. Thromb Res 1988; 49: 169-79
• 19 Graham JB. Genotype assignment (carrier detection) in the haemophilias. Clin Elaematol 1979; 8: 115-45