Two spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).
For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.
It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.
References
1
Axelsson G,
Korsan-Bengtsen K,
Waldenstrom J.
1976; Prothrombin determination by means of a chromogenic peptide substrate. Thrombosis and Haemostasis 36: 517
3
Bergstrom K,
Blomback M.
1974; Determination of plasma prothrombin with a reaction rate analyzer using a synthetic substrate. Thrombosis Research 4: 719
4
Bergstrom K,
Egberg N.
1978; Determination of vitamin K sensitive coagulation factors in plasma. Studies on three methods using synthetic chromogenic substrates Thrombosis Research 12: 531
5
Franza BR,
Aronson DL,
Finlayson JS.
1975; Activation of human prothrombin by a procoagulant fraction from the venom of Echis carinatus. Identification of a high molecular weight intermediate with thrombin activity Journal of Biological Chemistry 250: 7057
6
Hellemans J,
Vorlat M,
Verstraete M.
1963; Survival time of prothrombin and factors VII, IX and X after completely synthesis blocking dosis of coumarin derivatives. British Journal of Haematology 9: 506
7
Kirchhof BR J,
Vermeer C,
Hemker HC.
1978; The determination of prothrombin using synthetic chromogenic substrates; choice of a suitable activator. Thrombosis Research 13: 219
8
Kornalik F,
Blomback B.
1975; Prothrombin activation induced by Ecarin - a prothrombin converting enzyme from Echis carinatus venom. Thrombosis Research 6: 53
9
Latallo ZS,
Teisseyre E.
1977. Amidolytic assay of prothrombin activated with ecarin, a procoagulant from Echis Carinatus Venom. In
WITT I.
(ed.)
New Methods for the Analysis of Coagulation Using Chromogenic Substrates. Walter de Gruyter; Berlin - New York: p 181
12
Róka L,
Koch R,
Bleyl H.
1977. Studies on the determination of prothrombin with S2160. In
WITT I.
(ed.)
New Methods for the Analysis of Coagulation Using Chromogenic Substrates. Walter de Gruyter; Berlin - New York: p 171
13
Schieck A,
Habermann E,
Kornalik F.
1972; The prothrombin activating principle from Echis carinatus venom II. Coagulation studies in vitro and in vivo. Naunyn-Schmiedebergs Archives of Pharmacology 274: 1
14
Svendsen L,
Blomback B,
Blomback M,
Olsson PI.
1972; Synthetic chromogenic substrates for determination of trypsin, thrombin and thrombin-like enzymes. Thrombosis Research 1: 267
15
Vermeer C,
Govers-Riemslag JW P,
Soute BA M,
Lindhout MJ,
Kop J,
Hemker HC.
1978; The role of blood clotting factor V in the conversion of prothrombin and decarboxy prothrombin into thrombin. Biochimica et Biophysica Acta 538: 521
16
Wuk EM,
Van Kahlé LH,
Jenkins CS P,
Ten Cate JW.
1978. The determination of prothrombin using an automated amidolytic technique. In Abstr. XVII Congress of the International Society of Hematology. Paris: 1978. p 862
17
Witt I.
1977. Determination of plasma prothrombin with chromozym TH. In
Witt I.
(ed.)
New Methods for the Analysis of Coagulation Using Chromogenic Substrates. Walter de Gruyter; Berlin - New York: p 155