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DOI: 10.1055/s-0037-1613440
In vivo pig models of venous thrombosis mimicking human disease
Publication History
Received
16 October 2002
Accepted after revision
21 November 2002
Publication Date:
07 December 2017 (online)
Summary
Most animal models of venous thrombosis involve acute thrombosis with hypercoagulability in small rodents. To better replicate human disease, we developed two models in the pig, a species similar to humans in size and in vascular and coagulation reactivity. One model involves de-endothelialisation with 50% or 80% stenosis and the other replacement of a venous segment by a Gore-Tex™ vascular prosthesis. Both models were tested with and without acute induced hypercoagulability (thromboplastin infusion). Thrombi obtained without thromboplastin infusion were composed of a multilayered platelet and a fibrin meshwork structure similar to that usually found in humans. With thromboplastin infusion, the thrombi were homogeneous fibrin structures imprisoning red blood cells. The high incidence of thrombosis obtained with the 80% stenosis model would be useful for studying anticoagulant treatments, whereas the low incidence with 50% stenosis would be useful for evaluating procoagulant effects of conditions or treatments. These new models shed further light on the development of venous thrombi under conditions similar to those seen in humans and may prove useful for investigating anticoagulant and procoagulant effects.
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References
- 1 Levi M, Dorffle-Melly J, Johnson GJ, Drouet L, Badimon L. Usefulness and limitations of animal models of venous thrombosis. Thromb Haemost 2001; 86 (05) 1331-3.
- 2 Arroyo JG, Dastgheib K, Hatchell DL. Antithrombotic effect of ticlopidine in an experimental model of retinal vein occlusion. Jpn J Ophthalmol 2001; 45 (04) 359-62.
- 3 Valji K, Bookstein JJ. Efficacy of adjunctive intrathrombic heparin with pulse spray thrombolysis in rabbit inferior vena cava thrombosis. Invest Radiol 1992; 27 (11) 912-7.
- 4 Giedrojc J, Krupinski K, Breddin HK, Bielawiec M. Interaction between the sulfated lactobionic acid (LW 10082) and other anti-thrombotic agents in animal thrombosis model. Pol J Pharmacol 1996; 48 (03) 317-22.
- 5 Raake W, Klauser RJ, Elling H, Zeiller P. Antithrombotic action of recombinant hirudin in a venous thrombosis model. Haemostasis 1991; 21 Suppl 1 127-32.
- 6 Edwards S, Betz A, James H, Thompson E, Yonkovich S, Sinha U. Differences between human and rabbit coagulation factor X-implications for in vivo models of thrombosis. Thromb Res 2002; 106 (01) 71
- 7 Wessler S. Studies in intravascular coagulation; Coagulation changes in isolated venous segments. J Clin Invest 1952; 31: 1011-4.
- 8 Millet J, Vaillot M, Theveniaux J, Brown NL. Experimental venous thrombosis induced by homologous serum in the rat. Thromb Res 1996; 81 (04) 497-502.
- 9 Bara L, Bloch MF, Samama MM. A comparative study of recombinant hirudin and standard heparin in the Wessler model. Thromb Res 1992; 68 (02) 167-74.
- 10 Prowse CV, Williams AE. A comparison of the in vitro and in vivo thrombogenic activity of factor IX concentrates using stasis (Wessler) and non-stasis rabbit models. Thromb Haemost 1980; 44 (02) 81-6.
- 11 Gray E, Tubbs J, Thomas S, Oates A, Boisclair M, Kemball-Cook G. et al. Measurement of activated factor IX in factor IX concentrates: correlation with in vivo thrombogenicity. Thromb Haemost 1995; 73 (04) 675-9.
- 12 Bacher P, Walenga JM, Iqbal O, Bajusz S, Breddin K, Fareed J. The antithrombotic and anticoagulant effects of a synthetic tripeptide and recombinant hirudin in various animal models. Thromb Res 1993; 71 (04) 251-63.
- 13 Roussi J, Andre P, Samama M, Pignaud G, Bonneau M, Laporte A. et al. Platelet functions and haemostasis parameters in pigs: absence of side effects of a procedure of general anaesthesia. Thromb Res 1996; 81 (03) 297-305.
- 14 Giles AR. Guidelines for the use of animals in biomedical research. Thromb Haemost 1987; 58 (04) 1078-84.
- 15 Ravanat C, Freund M, Dol F, Cadroy Y, Roussi J, Incardona F. et al. Cross-reactivity of human molecular markers for detection of prethrombotic states in various animal species. Blood Coagul Fibrinolysis 1995; 6 (05) 446-55.
- 16 Didisheim P. Animal models useful in the study of thrombosis and antithrombotic agents. Prog Hemost Thromb 1972; 1: 165-97.
- 17 Aronson DL, Thomas DP. Experimental studies on venous thrombosis: effect of coagulants, procoagulants and vessel contusion. Thromb Haemost 1985; 54 (04) 866-70.
- 18 Rizza CR.. Haemostasis and blood coagulation. In McGee JO, Isaacson PG, Wright NA. editors Oxford Textbook of Pathology. Oxford University Press; Oxford: 1992: 502-9.
- 19 Lindop GBM, Percy-Robb IW, Walker ID.. Disturbances of body fluids. Haemostasis and the flow of blood. In MacSween RNM, Whaley K. editors Muir's textbook of pathology; Arnold, London: 1992: 73-111.
- 20 Kroger K, Schelo C, Gocke C, Rudofsky G. Colour Doppler sonographic diagnosis of upper limb venous thromboses. Clin Sci (Lond) 1998; 94 (06) 657-61.
- 21 Kroger K, Fischer A, Hinrichs A, Gocke C, Rudofsky G. Patients with a malignant tumor have more extended thrombosis than patients without. Angiology 1998; 49 (11) 923-8.
- 22 Loud PA, Klippenstein DL. Lower extremity deep venous thrombosis in cancer patients: correlation of presenting symptoms with venous sonographic findings. J Ultrasound Med 1998; 17 (11) 693-6.
- 23 Kazmers A, Groehn H, Meeker C. Acute calf vein thrombosis: outcomes and implications. Am Surg 1999; 65 (12) 1124-7.
- 24 Ricci P, Cantisani V, Biancari F, Drud FM, Coniglio M, Di Filippo A. et al. Contrast-enhanced color Doppler US in malignant portal vein thrombosis. Acta Radiol 2000; 41 (05) 470-3.
- 25 Carrie D, Caranobe C, Boneu B. A comparison of the antithrombotic effects of heparin and of low molecular weight heparins with increasing antifactor Xa/antifactor IIa ratio in the rabbit. Br J Haematol 1993; 83 (04) 622-6.
- 26 Cadroy Y, Hanson SR, Harker LA. Anti-thrombotic effects of synthetic pentasaccha-ride with high affinity for plasma antithrombin III in non-human primates. Thromb Haemost 1993; 70 (04) 631-5.