Subscribe to RSS
DOI: 10.1055/s-0038-1650178
The Inhibitor of Prothrombin Conversion in Plasma of Patients on Oral Anticoagulant Treatment
Publication History
Received 13 January 1981
Accepted 20 March 1980
Publication Date:
06 July 2018 (online)
Summary
Pooled plasma of patients under stable oral anticoagulation has been analysed with respect to the presence of the vitamin-K dependent factors (factors II, VII, IX and X). Of all factors 1.5-2 times more antigen than procoagulant activity was present. The concentration of factors II, X (measured spectrophotometrically) and VII is about 0.25 U/ml while factor IX is slightly higher. Coagulation assays of factor X always gave lower values than the spectrophotometric assay. This discrepancy was not influenced by the removal of either factor II-factor VII- or factor IX antigen. However, when the factor X antigen was replaced by normal factor X, all factor X assays gave identical results, indicating that PIVKA X is responsible for these discrepancies. Using the technic of the Thrombotest-dilution curve it was shown that PIVKA X is the factor that causes the abnormal prolongation of ox-brain prothrombin time in these plasmas.
-
References
- 1 Hemker HC, Veltkamp JJ, Hensen A, Loeliger EA. Nature of prothrombin biosynthesis: preprothrombinaemia in vitamin-K deficiency. Nature 1963; 200: 589-590
- 2 Loeliger EA, Esch B, van der, Mattem MJ, Brabander ASAden. Behaviour of factors II, VII, IX and X during long-term treatment with coumarin. Thromb Diath Haemorrh 1963; 09: 74-89
- 3 Loeliger EA, Hensen A, Mattem MJ, Hemker HC. Behaviour of factors II, VII, IX and X in bleeding complications during long-term treatment with coumarin. Thromb Diath Haemorrh 1964; 10: 278-281
- 4 Owren PA. Tests for control of anticoagulant therapy. Thromb Diath Haemorrh 1964; S13: 371-378
- 5 Hemker HC, Siepel TV, Altman R, Loeliger EA. Kinetic aspects of the interaction of blood clotting enzymes. II. The relation between clotting time and plasma concentration in prothrombin-time estimations. Thromb Diath Haemorrh 1967; 17: 349-357
- 6 Hemker HC, Veltkamp JJ, Loeliger EA. Kinetic aspects of the interaction of blood clotting enzymes. III. Demonstration of an inhibitor of prothrombin conversion in vitamin K deficiency. Thromb Diath Haemorrh 1968; 19: 346-363
- 7 Girolami A, Dal BoZanon R, Sticchi A. Apparent “inhibition” as tested by means of the dilution curve system in patients with clotting defect due to liver damage. Blut 1977; 35: 247-252
- 8 Larrieu MJ, Meyer D. Abnormal factor IX during anticoagulant treatment. Lancet 1970; 02: 1085
- 9 Denson KWE. The levels of factors II, VII, IX and X by antibody neutralization techniques in the plasma of patients receiving phenindione therapy. Br J Haematol 1971; 20: 643-648
- 10 Prydz H, Gladhaug Å. Factor X immunological studies. Thromb Diath Haemorrh 1971; 25: 157-165
- 11 Veltkamp JJ, Muis H, Muller AD, Hemker HC, Loeliger EA. Additional evidence for the existence of a precursor molecule of the prothrombin complex in oral anticoagulants. Thromb Diath Haemorrh 1971; 25: 312-315
- 12 Thompson AR. Factor IX antigen by radioimmunoassay. Abnormal factor IX protein in patients on warfarin therapy and with hemophilia B. J Clin Invest 1977; 59: 900-910
- 13 Fair DS, Plow EF, Edgington TS. Combined functional and immunochemical analysis of normal and abnormal human factor X. J Clin Invest 1979; 64: 884-894
- 14 Ganrot PO, Niléhn JE. Plasma prothrombin during treatment with dicumarol. II. Demonstration of an abnormal prothrombin fraction. Scand J Clin Lab Invest 1968; 22: 23-28
- 15 Ørstavik KH, Laake K. Factor IX in warfarin treated patients. Thromb Res 1978; 13: 207-218
- 16 Bertina RM, Veltkamp JJ. A genetic variant of factor IX with decreased capacity for Ca2+binding. Br J Haematol 1979; 42: 623-635
- 17 Prydz H. Vitamin K-dependent clotting factors. Semin Thromb Hemostas 1977; 4: 1-14
- 18 Suttie JW. The metabolic role of vitamin K. Fed Proc 1980; 39: 2730-2735
- 19 Stenflo J, Femlund P, Egan W, Roepstorff P. Vitamin-K dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci USA 1974; 71: 2730-2733
- 20 Reekers PPM, Lindhout MJ, Kop-Klaassen BH M, Hemker HC. Demonstration of three anomalous plasma proteins induced by a vitamin K antagonist. Biochim Biophys Acta 1973; 317: 559-562
- 21 Lindhout MJ, Kop-Klaassen BH, Kop JM M, Hemker HC. Purification and properties of phenprocoumon-induced decarboxy-factor X from bovine plasma. Comparison to normal factor X. Biochem Biophys Acta 1978; 533: 302-317
- 22 Loeliger EA, Halem-Visser LP van. Biological properties of the thromboplastins and plasmas included in the ICTH/ICSH collaborative study on prothrombin time standardization. Thromb Haemostas 1979; 42: 1115-1127
- 23 Girolami A, Celia G, Patrassi GM, Dal BoZanon R, Fabris F. About the significance or insignificance of coumarin-induced pre-factors. Thromb Haemostas 1980; 43: 225
- 24 Veltkamp JJ, Drion EF, Loeliger EA. Detection of the carrier state in hereditary coagulation disorders. I. Thromb Diath Haemorrh 1968; 19: 279-303
- 25 Owren PA. A quantitative one stage method for the assay of prothrombin. Scand J Clin Lab Invest 1949; 19: 81-83
- 26 Bertina RM, Marel-van NieuwkoopW van der, Loeliger EA. Spectrophotometric assays of prothrombin in plasma of patients using oral anticoagulants. Thromb Haemostas 1979; 42: 1296-1305
- 27 Bertina RM, Loeliger EA. The potential use of chromogenic assays in the routine monitoring of oral anticoagulant therapy. In: Lynen HP, Collen D, Verstraete M. (eds.), Synthetic substrates in clinical blood coagulation . Martinus Nijhoff Publishers; The Hague-Boston-London: 1980. p 13-23
- 28 Bertina RM, Linden IK van der. Inhibitor-neutralisation assay and electro-immuno assay of human factor IX (Christmas factor). Clin Chim Acta 1977; 77: 275-288
- 29 Bertina RM, Orlando M, Tiedemann-Alderkamp GH J. Preparation of a human factor VII deficient plasma. Thromb Res 1978; 13: 537-541
- 30 Mertens K, Bertina RM. Pathways in the activation of human coagulation factor X. Biochem J 1980; 185: 647-658
- 31 Loeliger EA, Halem-Visser LP van, Hemker HC. Plasma free of factors II, VII, IX and X, need for high speed centrifugation after A1 (OH)3absorption. Thromb Diath Haemorrh 1973; 29: 211-212
- 32 Wijk EM van, Kahlé LH, Cate JW ten. Mechanized amidolytic technique for determination of factor X and factor-X antigen, and its applications to patients being treated with oral anticoagulants. Clin Chem 1980; 26: 885-890
- 33 Kisiel W. Human plasma protein C. Isolation, characterization, and mechanism of activation by α-thrombin. J Clin Invest 1979; 64: 761-769
- 34 Di ScipioRG, Davie EW. Characterization of protein S, a γ-carboxy-glutamic acid containing protein from bovine and human plasma. Biochemistry 1979; 18: 899-904
- 35 Prowse CV, Esnouf MP. The isolation of a new warfarin sensitive protein from bovine plasma. Biochem Soc Trans 1977; 05: 255-265
- 36 Bachmann F, Duckert F, Koller F. The Stuart-Prower factor assay and its clinical significance. Thromb Diath Haemorrh 1958; 02: 24-38
- 37 Hemker HC, Swart AC W, Alink AJ M. Artificial reagents for factor VII and factor X, a computer programme for obtaining reference tables for one-stage determinations in the extrinsic system. Thromb Diath Haemorrh 1972; 27: 205-211