Indirect Measurement of Streptokinase Concentration in the Plasma of Patients Undergoing Fibrinolytic Treatment^[*]

Summary

A new method of determining streptokinase concentrations on a quantitative basis in the plasma of patients undergoing streptokinase infusion is demonstrated. The principle of this method is based on the clot lysis time recorded by the thrombo-elastograph. The test clot constituents were bovine fibrin, bovine plasminogen, human euglobulin, EDTA, human plasma (with unknown streptokinase quantity) and thrombin. As plasminogen (euglobulin) and fibrinogen were present in the test coagulum in rather high concentrations (fixed excess) no interference with changing plasminogen and fibrinogen levels of the patient’s plasma was observed. Further, due to high EDTA concentrations, no interaction with platelet functions and coagulation factors took place. The standard error of measuring 5 u of streptokinase in one ml of human plasma was determined at s = ±0.47 u/ml.

Eleven patients undergoing fibrinolytic treatment with streptokinase were monitored by streptokinase determination in the plasma. In this group of patients, streptokinase concentration values varying between 15 and 0.5 units/ml plasma were measured. One striking feature was the continuous decrease in streptokinase concentration in the plasma, in spite of unchanged streptokinase infusion rates. This observation was consistent in regimens with both large (100,000 u/h) and small (30,000 u/h) streptokinase infusion rates. No explanation is available for this observation up to now. A rise in circulating anti-streptokinase contents was precluded. Possibly, an accelerated streptokinase metabolism rate in the course of long-term streptokinase administration may be involved.

^* Supported by Grants from Verein zur Bekampfung der GefaLlerkrankungen e. V., Engelskirchen.

• References

• 1 Auel H, Martin M. 1974; Plasminogengehalt eines im Handel befindlichen Rinderplasminogens. Z. klin. Chem. klin. Biochem 12: 385-388.
• 2 Christensen L. R. 1949; Methods for measuring the activity of components of the streptococcal fibrinolytic system, and streptococcal desoxyribonuclease. Journal of Clinical Investigations 28: 163.
• 3 Deutsch E, Fischer M. 1960; Die Wirkung intravenös applizierter Streptokinase auf Fibrinolyse und Blutgerinnung. Thrombosis et Diathesis Haemorrhagica 06: 482.
• 4 Egberg N, Blombäck M, Johnson H, Abildgaard T. l, Blombäck B, Diener G, Ekeström S, Göransson L, Johansson S. A, McDonagh J, McDonagh R, Nilsson S. E, Norderström S, Olsson P, Wiman B. 1971. Clinical and experimental studies on Reptilase, 379-396. In: Mammen E. F, Anderson G. F, Barnhart M. I. (eds.) Thrombolytic Therapy. F. K. Schattauer-Verlag; Stuttgart-New York: 1971.
• 5 Göttinger E, Vinazzer H. 1964; Der Einfluß von ÄDTA auf die Blutgerinnung. Thrombosis et Diathesis Haemorrhagica 11: 513.
• 6 Gram H. C. 1921; A new method for the determination of the fibrin percentage in blood and plasma. Journal of Biological Chemistry 49: 279.
• 7 Hyers T. M. 1971. Urokinase in the treatment of pulmonary embolism. In: Mammen E. F, Anderson G. F, Barnhart M. Thrombolytic Therapy. F. K. Schattauer-Verlag; Stuttgart-New York: 165.
• 8 von Kaulla K. N, McDonald T. S. 1958; The effect of heparin on components of the human fibrinolytic system. Blood 13: 811.
• 9 Lassen M. 1952; Heat denaturisation of plasminogen in the fibrinplate method. Acta physica scandinavica 27: 371.
• 10 Latallo Z. S, Lopaciuk S. 1972. New approach to thrombolytic therapy. The use of defibrase in connection with streptokinase. Lecture held at the Conference on the Intravascular Coagulation and Fibrinolysis. Sherbrooke; Canada.:
• 11 Martin M. 1973; Studies on activator formation in human plasma with streptokinase. I. Experimental studies. Thrombosis et Diathesis Haemorrhagica SO: 393.
• 12 Martin M, Schoop W, Engelken H. J, Tambert F. 1973. Gerinnungsphysiologische und klinische Erfahrungen mit Defibrase, 128-138. In: Ehringer H. (Hrsg.) Fortschritte der konservativen Therapie der peripher ena rteriellen Verschlußkrankheit. Verlag Hans Huber, Bern; Stuttgart, Wien: 1974.
• 13 Martin M, Schoop W, Zeitler E. 1970a) Thrombolyse bei chronischer Arterio-pathie. Verlag Hans Huber; Bern, Stuttgart, Wien.:
• 14 Martin M, Schoop W, Zeitler E. 1970b Streptokinase in chronic arterial occlusive disease. Journal of the American Medical Association 211: 1169.
• 15 Niewiarowski S, Regoeczi E, Gwendolyn J. S, Seny A. F, Mustard J. F. 1972; Platelet interaction with polymerizing fibrin. Journal of Clinical Investigation 51: 685.
• 16 Verstraete M, Amery A, Vermylen J, de Vreker R. 1964; Practical method for thrombolytic therapy with streptokinase. Maintainance of nearly complete plasminogen depletion associated with high circulating activator activity. British Medical Journal 01: 675.
• 17 Zucker M. B, Borelli J. 1958; Some effects of divalent cations on the clotting mechanism and the platelets of EDTA-blood. Journal of Applied Physiology 12: 453.