Subscribe to RSS
DOI: 10.1160/TH06-07-0370
A global assay of haemostasis which uses recombinant tissue factor and tissue-type plasminogen activator to measure the rate of fibrin formation and fibrin degradation in plasma
Financial support: This study was supported by funds from Karolinska Institutet, the Swedish Society of Medicine and the Magnus Bergvall Foundation.Publication History
Received
06 July 2006
Accepted after resubmission
20 July 2007
Publication Date:
01 December 2017 (online)
Summary
The global assay of Overall Haemostasis Potential we previously described has been refined. The coagulation cascade in plateletpoor plasma is triggered by adding a minimal dose of recombinant tissue factor together with purified phospholipids and calcium; fibrinolysis is initiated by adding recombinant tissue type-plasminogen activator in a concentration similar to what can be obtained during thrombolysis. Numerical differentials of optical densities reflecting rates of fibrin formation and degradation are calculated by a new software, and the Coagulation Profile (Cp) and the Fibrinolysis Profile (Fp) are determined. The combined effect of these counteractive systems is expressed as a ratio of Cp to Fp, called the Overall Haemostasis Index. Commercially available coagulant-deficient patient plasma samples and plasma with various amounts of added PAI-1 are examined; changes of fibrin turbidity demonstrate that this assay can determine Cp and Fp in a physiologically relevant way. Increased Cp and decreased Fp in prothrombotic patients, as well as expected effects of heparin or a thrombin inhibitor on Cp and Fp, suggest that our method can detect hypercoagulability and assist in monitoring antithrombotic treatment. Ongoing studies will show whether this simple assay can be of value in clinical routine.
-
References
- 1 Lawson JH, Kalafatis M, Stram S. et al. A model for the tissue factor pathway to thrombin. I. An empirical study.. J Biol Chem 1994; 269: 23357-23366.
- 2 Downey C, Kazmi R, Toh CH. Novel and diagnostically applicable information from optical waveform analysis of blood coagulation in disseminated intravascular coagulation.. Br J Haematol 1997; 98: 68-73.
- 3 Hemker HC, Giesen P, AlDieri R. et al. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability.. Pathophysiol Haemost Thromb 2002; 32: 249-253.
- 4 Smith AA, Jacobson L J, Miller B I. et al. A new euglobulin clot lysis assay for global fibrinolysis.. Thromb Res 2003; 112: 329-337.
- 5 Sorensen B, Johansen P, Christiansen K. et al. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation.. J Thromb Haemost 2003; 1: 551-558.
- 6 He S, Antovic A, Blombäck M. A simple and rapid laboratory method for determination of haemostasis potential in plasma – II. Modifications for use in routine laboratories and research work.. Thromb Res 2001; 103: 355-361.
- 7 Antovic A, Blomback M, Sten-Linder M. et al. Identifying hypocoagulable states with a modified global assay of overall haemostasis potential in plasma.. Blood Coagul Fibrinolysis 2005; 16: 585-596.
- 8 Schneider M, Nesheim M. Reversible inhibitors of TAFIa can both promote and inhibit fibrinolysis.. J Thromb Haemost 2003; 1: 147-154.
- 9 Li N, He S, Blomback M. et al. Platelet activity, coagulation, and fibrinolysis during exercise in healthy males: effects of thrombin inhibition by argatroban and enoxaparin.. Arterioscler Thromb Vasc Biol 2007; 27: 407-413.
- 10 Eriksson BI, Arfwidsson AC, Frison L. et al. A dose-ranging study of the oral direct thrombin inhibitor, ximelagatran, and its subcutaneous form, melagatran, compared with dalteparin in the prophylaxis of thromboembolism after hip or knee replacement: METHRO I.. Thromb Haemost 2002; 87: 231-237.
- 11 Ersdal E, Schutzer K, Lonnerstedt C. et al. Plasma concentration of melagatran after ingestion of different doses of the drug.. Clin Drug Invest 2005; 25: 125-133.
- 12 He S, Cao H, Antovic A. et al. Modifications of flow measurement to determine fibrin gel permeability and the preliminary use in research and clinical materials.. Blood Coagul Fibrinolysis 2005; 16: 61-67.
- 13 Collet JP, Park D, Lesty C. et al. Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy.. Arterioscler Thromb Vasc Biol 2000; 20: 1354-1361.
- 14 Collet JP, Soria J, Mirshahi M. et al. Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure.. Blood 1993; 82: 2462-2469.
- 15 Hoffman M, Monroe DM. A cell-based model of hemostasis.. Thromb Haemost 2001; 85: 958-965.
- 16 Tebbe U, Seifried E, Carlsson J. et al. Thrombolysis using consecutive high dose bolus and infusion of alteplase in a patient with acute massive pulmonary embolism.. Blood Coagul Fibrinolysis 1992; 3: 475-480.
- 17 Verstraete M. In: Thrombolysis in Cardiovascular Disease,. New York and Basel:: Marcel Dekker,; 1989: 69-86.
- 18 Kaufman RJ, Antonarakis SE, Fay PJ. Factor VIII and hemophilia A.. In: Textbook of Haemostasis and Thrombosis, Basic principles and clinical practice.. 4th ed. Lippincott, Willams & Wilkins; 2000: 135-156.
- 19 Franchini M, Veneri D. Inherited thrombophilia: an update.. Clin Lab 2005; 51: 357-365.
- 20 Nordt TK, Peter K, Ruef J. et al. Plasminogen activator inhibitor type-1 (PAI-1) and its role in cardiovascular disease.. Thromb Haemost 1999; 82: 14-18.
- 21 Willams S, Fatah K, Ivert T. et al. The effect of acetylsalicylic acid on fibrin gel lysis by tissue plasminogen activator.. Blood Coagul Fibrinolysis 1995; 6: 718-725.