Effect of Thrombin Inhibitors and a Glycoprotein IIb/IIIa Receptor Antagonist in an Ex Vivo Human Experimental Thrombosis Model

Kaweh Zokai; Lukas Piazolo; Job Harenberg

doi:10.1055/s-2001-17963

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2001; 27(5): 531-536
DOI: 10.1055/s-2001-17963

Effect of Thrombin Inhibitors and a Glycoprotein IIb/IIIa Receptor Antagonist in an Ex Vivo Human Experimental Thrombosis Model

Kaweh Zokai, Lukas Piazolo, Job Harenberg

First Department of Medicine, University Hospital, Mannheim, Germany

Abstract

ABSTRACT

The development of new antithrombotic drugs to inhibit the blood coagulation system and to block receptors of platelets represents an important area of medical research. The results of the efficacy in animal models are of critical importance for the further development of these compounds for human use. The transferability of such data from animal to human species still remains controversial. The antithrombotic effects of direct thrombin inhibitors and a glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist were investigated in an experimental thrombosis model using human blood in order to analyze the feasibility of such a model.

KEYWORD

Thrombosis model - GPIIb/IIIa antagonist - thrombin inhibitors - blood coagulation - platelets

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References

REFERENCES

1 Hara T, Yokoyama A, Morishima Y, Kunitada S. Species differences in anticoagulant and anti-Xa activity of DX-9065a, a highly selective factor Xa inhibitor. Thromb Res . 1995; 80 99-104
2 Tapparelli C, Metternich R, Gfeller P, Gafner B, Powling M. Antithrombotic activity in vivo of SDZ 217-766, a low-molecular weight thrombin inhibitor in comparison to heparin. Thromb Haemost . 1995; 73 641-647
3 Dickneite G, Seiffge D, Diehl K H. Pharmacological characterization of a new 4-amidinophenylalanine thrombin-inhibitor (CRC 220). Thromb Res . 1995; 77 357-368
4 Shirakura S, Higo K, Takeda M, Karasawa A. Antithrombotic effects of KW-3635, a thromboxane A2-receptor antagonist, in guinea pigs. Jpn J Pharmacol . 1994; 65 93-98
5 Coller B S. GPIIb/IIIa antagonists: pathophysiologic and therapeutic insights from studies of c7E3 Fab. Thromb Haemost . 1997; 78 730-735
6 Ammar T, Scudder L E, Coller B S. In vitro effects of platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab on the activated clotting time. Circulation . 1997; 95 614-617
7 Reverter J C, Beguin S, Kessels H. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. J Clin Invest . 1996; 98 863-874
8 Aguejouf O, Imbault P, Jourdan A. Experimental models of arterial thrombosis. Ann Cardiol Angeiol (Paris) . 1995; 44 109-118
9 Chesebro J H, Fuster V. Thrombosis in unstable angina. N Engl J Med . 1992; 327 192-194
10 Chierchia S, Patrono C. Role of platelets and vascular eicosanoids in the pathophysiology of ischemic heart disease. Fed Proc . 1987; 46 81(Abst)
11 Ruggeri Z M. New insights into mechanism of platelet adhesion and aggregation. Semin Hematol . 1994; 31 229-239
12 Sixma J J. Interaction of blood platelets with the vessel wall. In: Bloom A, Forbes CD, ed. Haemostasis and Thrombosis, 3rd ed New York: Churchill Livingstone 1994: 259-285
13 Jaffe E A. Cell biology of endothelial cells. Hum Pathol . 1987; 18 234-239
14 DeGroot P G, Sixma J J. Platelet adhesion. Br J Haematol . 1990; 75 308-312
15 Gray E, Tubbs J, Thomas S. Measurement of activated factor IX in factor IX concentrates: correlation with in vivo thrombogenicity. Thromb Haemost . 1995; 73 675-679
16 Orvim U, Barstad R M, Vlasuk G P, Sakariassen K S. Effect of selective factor Xa inhibition on arterial thrombus formation triggered by tissue factor/factor VIIa or collagen in an in vitro model of shear-dependent human thrombogenesis. Arterioscler Thromb Vasc Biol . 1995; 15 2188-2194
17 Hirigoyen M B, Zhang W X, Weinberg H. A standardized model of microvenous thrombosis. J Reconstr Microsurg . 1995; 11 455-459
18 Delon-Martin C, Vogt C, Chignier E. Venous thrombosis generation by means of high-intensity focused ultrasound. Ultrasound Med Biol . 1995; 21 113-119
19 Krupinski K, Ferber H, Breddin H K, Bielawiec M. The antithrombotic effect of thromboxane receptor antagonist HN 11500 on thrombus formation in laser thrombosis model and platelet function tests. Acta Haematol Pol . 1994; 25 235-242
20 Jourdan A, Aguejouf O, Imbault P, Doutremepuich F, Inamo J. Experimental thrombosis model induced by free radicals. Application to aspirin and other different substances. Thromb Res . 1995; 79 109-123
21 Saniabadi A R, Umemura K, Matsumoto N, Sakuma S, Nakashima M. Vessel wall injury and arterial thrombosis induced by a photochemical reaction. Thromb Haemost . 1995; 73 868-872
22 The EPIC Investigators. Use of monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high risk coronary angioplasty. N Engl J Med . 1994; 330 956-961
23 The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low dose heparin during percutaneous coronary revascularization. N Engl J Med . 1997; 336 1689-1696
24 The CAPTURE Investigators. Randomized placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet . 1997; 349 1429-1435
25 The RAPPORT Investigators. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation . 1998; 98 734-741
26 Harenberg J, Schuler M, Waibel S, Heptner W, Zimmermann R. Influence of low molecular weight heparin on fibrin formation and platelet aggregation. Haemostasis . 1985; 15 29-30
27 Harenberg J. Thrombin-antithrombin (TAT) complexes. In: Jespersen J, Bertina RM, Haverkate F, eds. ECAT Assay Procedures. Laboratory Techniques in Thrombosis. A Manual. 2nd ed. Boston: Kluwer Academic Publishers 1998: 209-216
28 Files J C, Malpass T W, Yee E K, Ritchie J L, Harker L A. Studies of human platelet alpha-granule release in vivo. Blood . 1981; 58 607-618