Interspecies differences in coagulation profile

Jolanta M. Siller-Matula; Roberto Plasenzotti; Alexander Spiel; Peter Quehenberger; Bernd Jilma

doi:10.1160/TH08-02-0103

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(03): 397-404
DOI: 10.1160/TH08-02-0103

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Interspecies differences in coagulation profile

Authors

Jolanta M. Siller-Matula

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria
Roberto Plasenzotti

²Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria
Alexander Spiel

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria
Peter Quehenberger

³Department of Biomedical Research, Medical University of Vienna, Austria
Bernd Jilma

¹Department of Clinical Pharmacology, Medical University of Vienna, Austria

Abstract

Summary

Many animals are used in research on blood coagulation and fibrinolysis, but the relevance of animal models to human health is often questioned because of differences between species. The objective was to find an appropriate animal species , which mimics the coagulation profile in humans most adequately. Species differences in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin generation was measured in platelet-poor plasma. Measurements were performed in blood from five different species: humans, rats, pigs, sheep and rabbits. In humans and sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05).Similarly, the endogenous thrombin potential (ETP) was in the same range in humans and sheep. The maximum clot firmness with or without thrombin stimulation was similar in rabbits and humans. The maximum lysis with or without thrombin stimulation was similar in humans and pigs. Significant species differences exist in the coagulation profile with or without thrombin stimulation. Most importantly, sheep had a clotting time most similar to humans and could thus be a suitable species for translational coagulation studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental species to study fibrinolytic pathway and support the usefulness of rabbits as a species for examining platelets.

Keywords

Clotting time - endogenous thrombin potential - species differences - thrombin

Full Text

References

References
1 Perel P, Roberts I, Sena E. et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. Br Med J 2007; 334: 197.
2 Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27: 81-90.
3 Spiel AO, Mayr FB, Firbas C. et al. Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans. J Thromb Haemost 2006; 04: 411-416.
4 Lang T, Bauters A, Braun SL. et al. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2005; 16: 301-310.
5 Anderson L, Quasim I, Soutar R. et al. An audit of red cell and blood product use after the institution of thromboelastometry in a cardiac intensive care unit. Transfus Med 2006; 16: 31-39.
6 Craft RM, Chavez JJ, Bresee SJ. et al. A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation. J Lab Clin Med 2004; 143: 301-309.
7 van Hylckama Vlieg A, Christiansen SC, Luddington R. et al. Elevated endogenous thrombin potential is associated with an increased risk of a first deep venous thrombosis but not with the risk of recurrence. Br J Haematol 2007; 138: 769-774.
8 Clauss A. Rapid physiological coagulation method in determination of fibrinogen. Acta Haematol 1957; 17: 237-246.
9 Langdell RD, Wagner RH, Brinkhous KM. Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assy procedure. J Lab Clin Med 1953; 41: 637-647.
10 Hoehle P. Zur Übertragbarkeit tierexperimenteller endovaskulärer Studien: Unterschiede der Gerinnungsund Fibrinolyse-Systeme bei häufig verwendeten Tierspezies im Vergleich zum Menschen. Thesis. 2000. RWTH Aachen University; Germany.:
11 Flight SM, Masci PP, Lavin MF. et al. Resistance of porcine blood clots to lysis relates to poor activation of porcine plasminogen by tissue plasminogen activator. Blood Coagul Fibrinolysis 2006; 17: 417-420.
12 Derian CK, Santulli RJ, Tomko KA. et al. Species differences in platelet responses to thrombin and SFLLRN. receptor-mediated calcium mobilization and aggregation, and regulation by protein kinases. Thromb Res 1995; 78: 505-519.
13 Sidhu P, Sutherland SB, Ganguly P. Interaction of thrombin with mammalian platelets. Am J Physiol 1979; 237: H353-358.
14 Nylander S, Mattsson C, Lindahl TL. Characterisation of species differences in the platelet ADP and thrombin response. Thromb Res 2006; 117: 543-549.
15 Mosnier LO, Bouma BN. Regulation of fibrinolysis by thrombin activatable fibrinolysis inhibitor, an unstable carboxypeptidase B that unites the pathways of coagulation and fibrinolysis. Arterioscler Thromb Vasc Biol 2006; 26: 2445-2453.
16 Wu KK. Soluble thrombomodulin and coronary heart disease. Curr Opin Lipidol 2003; 14: 373-375.
17 Bajzar L, Nesheim M, Morser J. et al. Both cellular and soluble forms of thrombomodulin inhibit fibrinolysis by potentiating the activation of thrombin-activable fibrinolysis inhibitor. J Biol Chem 1998; 273: 2792-2798.
18 Wielders S, Mukherjee M, Michiels J. et al. The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypocoagulability. Thromb Haemost 1997; 77: 629-636.
19 Andrew M, Ofosu F, Fernandez F. et al. A low molecular weight heparin alters the fetal coagulation system in the pregnant sheep. Thromb Haemost 1986; 55: 342-346.
20 Connell JM, Khalapyan T, Al-Mondhiry HA. et al. Anticoagulation of juvenile sheep and goats with heparin, warfarin, and clopidogrel. Asaio J 2007; 53: 229-237.
21 Mottaghy K, Oedekoven B, Poppel K. et al. Heparin free long-term extracorporeal circulation using bioactive surfaces. ASAIO Trans 1989; 35: 635-637.
22 Berny PJ, de Oliveira LA, Videmann B. et al. Assessment of ruminal degradation, oral bioavailability, and toxic effects of anticoagulant rodenticides in sheep. Am J Vet Res 2006; 67: 363-371.
23 Oedekoven B, Bey R, Mottaghy K. et al. Gabexate mesilate (Foy) as an anticoagulant in extracorporeal circulation in dogs and sheep. Thromb Haemost 1984; 52: 329-332.
24 Shen LL, Barlow GH, Holleman WH. Differential activities of heparins in human plasma and in sheep plasma. Effects of heparin molecular sizes and sources. Thromb Res 1978; 13: 671-679.
25 Karges HE, Funk KA, Ronneberger H. Activity of coagulation and fibrinolysis parameters in animals. Arzneimittelforschung 1994; 44: 793-797.
26 Tillman P, Carson SN, Talken L. Platelet function and coagulation parameters in sheep during experimental vascular surgery. Lab Anim Sci 1981; 31: 263-267.
27 Massicotte P, Mitchell L, Andrew M. A comparative study of coagulation systems in newborn animals. Pediatr Res 1986; 20: 961-965.
28 Addonizio Jr. VP, Edmunds Jr. LH, Colman RW. The function of monkey (M. mulatta) platelets compared to platelets of pig, sheep, and man. J Lab Clin Med 1978; 91: 989-997.
29 Burke SE, Lefer AM, Nicolaou KC. et al. Responsiveness of platelets and coronary arteries from different species to synthetic thromboxane and prostaglandin endoperoxide analogues. Br J Pharmacol 1983; 78: 287-292.
30 Read MS, Potter JY, Brinkhous KM. Venom coagglutinin for detection of von Willebrand factor activity in animal plasmas. J Lab Clin Med 1983; 101: 74-82.
31 Prince MR, Salzman EW, Schoen FJ. et al. Local intravascular effects of the nitinol wire blood clot filter. Invest Radiol 1988; 23: 294-300.
32 Grabowski EF, Didisheim P, Lewis JC. et al. Platelet adhesion to foreign surfaces under controlled conditions of whole blood flow: human vs rabbit, dog, calf, sheep, pig, macaque, and baboon. Trans Am Soc Artif Intern Organs 1977; 23: 141-151.
33 Hara T, Yokoyama A, Morishima Y. et al. Species differences in anticoagulant and anti-Xa activity of DX-9065a, a highly selective factor Xa inhibitor. Thromb Res 1995; 80: 99-104.
34 Niitsu Y, Jakubowski JA, Sugidachi A. et al. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 2005; 31: 184-194.
35 Bijnens AP, Knockaert I, Cousin E. et al. Expression and characterization of recombinant porcine plasminogen activator inhibitor-1. Thromb Haemost 1997; 77: 350-356.
36 Marbet GA, Eichlisberger R, Duckert F. et al. Side effects of thrombolytic treatment with porcine plasmin and low dose streptokinase. Thromb Haemost 1982; 48: 196-200.
37 Cliffton EE, Cannamela DA. Proteolytic and fibrinolytic activity of serum; activation by streptokinase and staphylokinase indicating dissimilarity of enzymes. Blood 1953; 08: 554-562.
38 Thiex R, Kuker W, Muller HD. et al. The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of in-tracerebral hemorrhage. Neurol Res 2003; 25: 254-262.
39 Hardaway RM, Williams CH, Marvasti M. et al. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med 1990; 18: 1413-1418.
40 Vasquez Y, Williams CH, Hardaway RM. Effect of urokinase on disseminated intravascular coagulation. J Appl Physiol 1998; 85: 1421-1428.
41 Jern C, Seeman-Lodding H, Biber B. et al. An experimental multiple-organ model for the study of regional net release/uptake rates of tissue-type plasminogen activator in the intact pig. Thromb Haemost 1997; 78: 1150-1156.
42 Nyberg A, Jakob SM, Seeman-Lodding H. et al. Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs. Acta Anaesthesiol Scand 2008; 52: 57-64.
43 McBane 2nd RD, Ford MA, Karnicki K. et al. Fibrinogen, fibrin and crosslinking in aging arterial thrombi. Thromb Haemost 2000; 84: 83-87.
44 Gurbel PA, Bliden KP, Guyer K. et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol 2005; 46: 1820-1826.
45 Hoefer IE, Grundmann S, Schirmer S. et al. Aspirin, but not clopidogrel, reduces collateral conductance in a rabbit model of femoral artery occlusion. J Am Coll Cardiol 2005; 46: 994-1001.
46 Golino P, Ambrosio G, Pascucci I. et al. Experimental carotid stenosis and endothelial injury in the rabbit: an in vivo model to study intravascular platelet aggregation. Thromb Haemost 1992; 67: 302-305.
47 van Gestel MA, Heemskerk JW, Slaaf DW. et al. In vivo blockade of platelet ADP receptor P2Y12 reduces embolus and thrombus formation but not thrombus stability. Arterioscler Thromb Vasc Biol 2003; 23: 518-523.
48 van Giezen JJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost 2005; 31: 195-204.
49 Greenbaum AB, Ohman EM, Gibson CM. et al. Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial. Am Heart J 2007; 154: 702-709.
50 Siller-Matula J, Schror K, Wojta J. et al. Thienopyridines in cardiovascular disease: focus on clopidogrel resistance. Thromb Haemost 2007; 97: 385-393.
51 Ngo TH, Declerck PJ. Immunological quantitation of rabbit plasminogen activator inhibitor-1 in biological samples: evidence that rabbit platelets do not contain PAI-1. Thromb Haemost 1999; 82: 1510-1515.
52 Unruh M, Grunow A, Gottstein C. Systemic coagulation parameters in mice after treatment with vascular targeting agents. Thromb J 2005; 03: 21.