Prothrombin Activation Fragment 1 + 2 and Thrombin Antithrombin III Complexes in Patients with Angina Pectoris: Relation to the Presence and Severity of Coronary Atherosclerosis

J Kienast; S G Thompson; C Raskino; H Pelzer; C Fechtrup; H Ostermann; J van de Loo

doi:10.1055/s-0038-1649625

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(04): 550-553
DOI: 10.1055/s-0038-1649625

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

Prothrombin Activation Fragment 1 + 2 and Thrombin Antithrombin III Complexes in Patients with Angina Pectoris: Relation to the Presence and Severity of Coronary Atherosclerosis

J Kienast

¹The Department of Internal Medicine, University of Münster, Germany

,

S G Thompson

²The Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom

,

C Raskino

²The Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom

,

H Pelzer

³The Behringwerke AG, Marburg, Germany

,

C Fechtrup

¹The Department of Internal Medicine, University of Münster, Germany

,

H Ostermann

¹The Department of Internal Medicine, University of Münster, Germany

,

J van de Loo

¹The Department of Internal Medicine, University of Münster, Germany

› Author Affiliations

Abstract

PDF Download

Summary

Plasma levels of the prothrombin activation fragment 1 + 2 (F 1 + 2) and of thrombin antithrombin III complexes (TAT) were determined in 225 patients with angina pectoris undergoing coronary angiography. Oral anticoagulant therapy was associated with a marked reduction in mean Fl + 2 (0.63 vs 1.62 nmol/l, p <0.0001) and TAT levels (1.65 vs 2.23 μg/1, p <0.0001). Omitting patients on oral anticoagulants, TAT values showed a positive association with patients’ age (r = 0.18; p = 0.01) and were slightly higher in patients with a history of myocardial infarction than in those without (2.47 vs 2.11 <g/l; p = 0.06). Both Fl + 2 and TAT levels were increased in patients with angiographically verified coronary atherosclerosis as compared to patients with angina and angiographically normal coronaries (Fl + 2: 1.76 vs 1.36 nmol/1, TAT: 2.35 vs 2.00 μg/1; p-values after adjusting for age, sex and past history of myocardial infarction 0.06 and 0.11 respectively). However, no graded relationship between Fl + 2 or TAT values and severity of atherosclerosis was observed. This study provides suggestive evidence that a procoagulant state exists in patients with angina pectoris and coronary atherosclerosis. Its relevance in predicting coronary ischaemic events needs to be studied prospectively.

PDF (246 kb)

References

References
1 DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303: 897-902
2 Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation 1985; 71: 699-708
3 Mizuno K, Satomura K, Miyamoto A, Arakawa K, Shibuya T, Arai T, Kurita A, Nakamura H, Ambrose JA. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med 1992; 326: 287-291
4 Meade TW, Miller GJ, Rosenberg RD. Characteristics associated with the risk of arterial thrombosis and the prethrombotic state. In: Thrombosis in Cardiovasular Disorders. Fuster V, Verstraete M. (eds) Philadelphia, PA: Saunders; 1992: 79-97
5 Lowe GDO, Drummond MM, Lorimer AR, Hutton I, Forbes CD, Prentice CRM, Barbenel JC. Relation between extent of coronary artery disease and blood viscosity. Br Med J 1980; 1: 673-674
6 Small M, Lowe GDO, Beattie JM, Hutton I, Lorimer AR, Forbes CD. Severity of coronary artery disease and basal fibrinolysis. Haemostasis 1987; 17: 305-311
7 Handa K, Kono S, Saku K, Sasaki H, Kawano T, Sasaki Y, Hiroki T, Arakawa K. Plasma fibrinogen levels as an independent indicator of severity of coronary atherosclerosis. Atherosclerosis 1989; 77: 209-213
8 Meade TW, Wilkes HC, Stirling Y, Brennan PJ, Kelleher C, Browne W. Randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease in men at high risk: design and pilot study. Eur Heart J 1988; 9: 836-843
9 Meade TW. Low-dose warfarin and low-dose aspirin in the primary prevention of ischemic heart disease. Am J Cardiol 1990; 65: 07c-11c
10 Bauer K, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Review article. Blood 1987; 70: 343-349
11 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemostas 1988; 59: 101-106
12 Pelzer H, Schwarz A, Stüber W. Determination of human prothrombin activation fragment 1 + 2 in plasma with an antibody against a synthetic peptide. Thromb Haemostas 1991; 65: 153-159
13 Schmitz-Huebner U, Thompson SG, Balleisen L, Fechtrup C, Grosse-Heitmeyer W, Kirchhof B, Most E, Müller US, Seiffert C, Seiffert D, van de Loo J. Lack of association between haemostatic variables and the presence or the extent of coronary atherosclerosis. Br Heart J 1988; 59: 287-291
14 Judkins MP. Percutaneous transfemoral selective coronary arteriography. Radiol Clin North Am 1968; 6: 467-492
15 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principle results of the Northwick Park Heart Study. Lancet 1986; II: 533-537
16 Lowe GDO. Blood rheology in arterial disease. Clin Sci 1986; 68: 419-425
17 Rosendaal FR, Varekamp I, Smit C, Bröcker-Vriends HJT, van Dyck H, Vandenbroucke JP, Hermans J, Suurmeijer TPBM, Briët E. Mortality and causes of death in Dutch haemophiliacs, 1973-86. Br J Haematol 1989; 71: 71-76
18 Douglas JT, Lowe GDO, Forbes CD, Prentice CRM. Plasma fibrinopeptide A and beta-thromboglobulin in patients with chest pain. Thromb Haemostas 1983; 50: 541-542
19 Van Hulsteijn H, Kolff J, Briët E, van der Laarse A, Bertina R. Fibrinopeptide A and beta thromboglobulin in patients with angina pectoris and acute myocardial infarction. Am Heart J 1984; 107: 39-45
20 Eisenberg PR, Sherman LA, Schectman K, Perez J, Sobel BE, Jaffe AS. Fibrinopeptide A: a marker of acute coronary thrombosis. Circulation 1985; 71: 912-918
21 Gallino A, Haeberli A, Baur HR, Straub PW. Fibrin formation and platelet aggregation in patients with severe coronary artery disease: relationship with the degree of myocardial ischemia. Circulation 1985; 72: 27-30
22 Théroux P, Latour JG, Léger-Gauthier C, De Lara J. Fibrinopeptide A and platelet factor levels in unstable angina pectoris. Circulation 1987; 75: 156-162
23 Boisclair MD, Lane DA, Wilde JT, Ireland H, Preston FE, Ofosu FA. A comparative evaluation of assays for markers of activated coagulation and/or fibrinolysis: thrombin-antithrombin complex, D-dimer and fibrinogen/fibrin fragment E antigen. Br J Haematol 1990; 74: 471-479
24 Nichols AB, Owen J, Kaplan KL, Sciacca RR, Cannon PJ, Nossel HL. Fibrinopeptide A, platelet factor 4, and β-thromboglobulin levels in coronary heart disease. Blood 1982; 60: 650-654
25 Small M, Lowe GDO, Rankin BM, Douglas JT, Beattie JM, Hutton I, Lorimer AR, Forbes CD. Basal fibrinolysis and coronarty artery disease. Haemostasis 1984; 14: 113 (Abstr)
26 Bauer KA, Barzegar S, Rosenberg RD. Influence of anticoagulants used for blood collection on plasma prothrombin fragment F1 + 2 measurements. Thromb Res 1991; 63: 617-628
27 Kaplan KL, Owen J. Radioimmunoassays of platelet alpha-granule proteins. In: Measurements of Platelet Function. Harker LA, Zimmerman TS. (eds) Edinburgh: Churchill Livingstone; 1983: 115-125
28 Pepper DS, Prowse CV. Beta-thromboglobulin and platelet factor 4. In: ECAT Assay Procedures. A Manual of Laboratory Techniques. Jespersen J, Bertina RM, Haverkate F. (eds) Lancaster: Kluwer Academic Publishers; 1992: 21-34
29 Conway EM, Bauer KA, Barzegar S, Rosenberg RD. Suppression of hemostatic system by oral anticoagulants in the blood of patients with thrombotic diatheses. J Clin Invest 1987; 80: 1535-1544
30 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative aging study. J Clin Invest 1987; 80: 1527-1534
31 Rybak ME, Lau HK, Tomkins B, Rosenberg RD, Handin RI. Relationship between platelet secretion and prothrombin cleavage in native whole blood. J Clin Invest 1981; 68: 405-412
32 Miller GJ, Wilkes HC, Meade TW, Bauer KA, Barzegar S, Rosen-berg RD. Haemostatic changes that constitute the hypercoagulable state. Lancet 1991; II: 1079
33 Radcliffe R, Nemerson Y. Activation and control of factor VII by activated factor X and thrombin. J Biol Chem 1975; 250: 388-395
34 Lowe GDO, Wood DA, Douglas JT, Riemersma RA, Macintyre CCA, Takase T, Tuddenham EGD, Forbes CD, Elton RA, Oliver MF. Relationship of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina. Thromb Haemostas 1991; 65: 339-343