Platelet Adhesion following the Administration of Tissue-type Plasminogen Activator and Its Reversal by Vitamin E in Rats

Summary

Thrombolytic therapy is known to induce platelet-related side effects. We used a parallel-plate flow chamber, which was connected to the femoral artery of the rat, to measure platelet adhesion ex vivo. A collagen-coated arterioarterial shunt between two carotid arteries was used to measure shunt patency duration as an index of antithrombotic efficacy. Tissue-type plasminogen activator (t-PA), vitamin E, and the combination of these two were intravenously administered for 60 min. Measurements were performed before drug administration, and at 30, 60, 120 min after the initiation of drug infusion. Our results indicated that (1) treatments with t-PA or t-PA/vitamin E prolonged the time to shunt occlusion at 30 and 60 min; (2) t-PA enhanced platelet adhesion at 60 and 120 min; (3) vitamin E tended to reduce platelet adhesion; (4) t-PA/vitamin E reduced the t-PA-enhanced platelet adhesion; (5) at the high-density area of platelet adhesion under t-PA treatment, the adherent platelets demonstrated severe morphological changes which could be blocked by vitamin E. These data suggest that t-PA may enhance platelet adhesion in rats and that this adverse effect can be suppressed by co-administration of vitamin E.

• References

• 1 Coller BS. Platelets and thrombolytic therapy. N Engl J Med 1990; 322: 33-42
• 2 Loscalzo J, Schafer AI. Anticoagulants, antiplatelet agents, and fibrinolysis. In: Vascular Medicine, a textbook for vascular biology and disease Loscalzo J, Creager MA, Dzau VJ. (eds) Boston: Little, Brown Co; 1992. pp 659-682
• 3 Gimple LW, Gold HK, Leinbach RC, Coller BS, Werner W, Yasuda T, Johns JA, Ziskind AA, Finkelstein D, Collen D. Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator. Circulation 1989; 80: 581-588
• 4 Kerins DM, Roy L, FitzGerald GA, Fitzgerald DJ. Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator. Circulation 1989; 80: 1718-1723
• 5 Ohlstein EH, Storer B, Fujita T, Shebuski RJ. Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. ThrombRes 1987; 46: 575-585
• 6 Shebuski RJ, Bloom JC, Sellers TS. Attenuation of the inhibitory effect of prostacyclin on platelet function after tissue plasminogen activator or streptokinase infusion in the rabbit. Fibrinolysis 1989; 3: 115-123
• 7 Rudd MA, George D, Amarante P, Vaughan DE, Loscalzo J. Temporal effects of thrombolytic agents on platelet function in vivo and their modulation by prostaglandins. Circul Res 1990; 67: 1175-1181
• 8 Steiner M. Effect of alpha-tocopherol administration on platelet function in man. Thromb Haemost 1983; 49: 73-77
• 9 Jandak J, Steiner M, Richardson PD. Alpha-tocopherol, an effective inhibitor of platelet adhesion. Blood 1989; 73: 141-149
• 10 Jen CJ, Lin JS. Direct observation of platelet adhesion to fibrinogen- and fibrin-coated surfaces. Am J Physiol 1991; 261: H1457-H1463
• 11 Jen CJ, Tai Y-W. Morphological study of platelet adhesion dynamics under whole blood flow conditions. Platelets 1992; 3: 145-153
• 12 Freund M, Mantz F, Nicolini P, Gachet C, Mulvihill J, Meyer L, Beretz A, Cazenave J-P. Experimental thrombosis on a collagen coated arterioarterial shunt in rats: a pharmacological model to study antithrombotic agents inhibiting thrombin formation and platelet deposition. Thromb Haemost 1993; 69: 515-521
• 13 Cazenave J-P, Packham MA, Mustard JF. Adherence of platelets to a collagen-coated surface: development of a quantitative method. J Lab Clin Med 1973; 82: 978-990
• 14 Goldsmith HL, Turitto VT. Rheological aspects of thrombosis and haemostasis: basic principles and applications. Thromb Haemost 1986; 55: 415-435
• 15 Split-plot factorial design: design with group-treatment coufounding. In: Experimental Design (2nd ed) Kirk RE. ed Belmont, CA: Brooks/Cole Publishing Company; 1982. pp 489-563
• 16 Fitzgerald DJ. Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. Am J Cardiol 1991; 68: 51B-57B
• 17 Michelson AD, Gore JM, Rybak ME, Cola CA, Barnard MR. Effect of in vivo infusion of recombinant tissue-type plasminogen activator on platelet glycoprotein Ib. Thromb Res 1990; 60: 421-424
• 18 Puri RN, Zhou F, Colman RF, Colman RW. Plasmin induced platelet aggregation is accompanied by cleavage of aggregin and indirectly mediated by calpain. Am J Physiol 1990; 259 C 862-868
• 19 Aronson DL, Chang P, Kessler CM. Platelet-dependent thrombin generation after in vitro fibrinolytic treatment. Circulation 1992; 85: 1706-1712
• 20 Rudd MA, George D, Johnstone MT, Moore RT, Collins L, Rabbani LE, Loscalzo J. Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy. Circ Res 1992; 70: 829-834
• 21 Wagner WR, Hubble JA. Local thrombin formation in an in vitro thrombosis model results in platelet recruitment and thrombus stabilization on collagen in heparinized blood. J Lab Clin Med 1990; 116: 636-650
• 22 Conforti G, Dominguez-Jimenez C, Ronne E, Hoyer-Hansen G, Dejana E. Cell surface plasminogen activation causes a retraction of in vitro cultured human umbilical vein endothelial cell monolayer. Blood 1994; 83: 0994-1005
• 23 Shi GY, Hau JS, Wang SJ, Wu IS, Change BI, Lin MT, Chow YH, Chang WC, Wing LYC, Jen CJ, Wu HL. Plasmin and the regulation of tissue-type plasminogen activator biosynthesis in human endothelial cells. J Biol Chem 1992; 267: 19363-19368
• 24 Steiner M. Vitamin E: more than an antioxidant. Clin Cardiol 1993; 16: 116-118
• 25 Kato Y, Watanabe K, Nakakura M, Hosokawa T, Hayakawa E, Ito K. Blood clearance and tissue distribution of various formulations of α-tocopherol injection after intravenous administration. Chem Pharm Bull 1993; 41: 599-604
• 26 Barker JE, Felix CC, Olinger GN, Kalyanaraman B. Myocardial ischemia and reperfusion: direct evidence for free radical generation by electron spin resonance spectroscopy. Proc Natl Acad Sci 1988; 85: 2786-2789
• 27 Davies SW, Ranjadayalan K, Wickens DG, Dormandy TL, Timmis AD. Lipid peroxidation associated with successful thrombolysis. Lancet 1990; 335: 741-743
• 28 Young IS, Purvis JA, Lightbody JH, Adgey AAJ, Trimble ER. Lipid peroxidation and antioxidant status following thrombolytic therapy for acute myocardial infarction. Eur Heart J 1993; 14: 1027-1033
• 29 Jen CJ, Li HM, Wang JS, Chen HI, Usami S. Flow-induced detachment of adherent platelets from fibrinogen-coated surface. Am J Physiol: Heart Circ Physiol 1996; 270