Download PDF
Thromb Haemost 2000; 83(02): 224-228
DOI: 10.1055/s-0037-1613790
Rapid Communication
Schattauer GmbH

Relationship of Cardiac Troponin T and Procoagulant Activity in Unstable Angina

Evangelos Giannitsis
1   From the Medizinische Klinik II der Medizinischen Universität zu Lübeck, Germany
,
Margit Müller Bardorff
1   From the Medizinische Klinik II der Medizinischen Universität zu Lübeck, Germany
,
Sybille Schweikart
1   From the Medizinische Klinik II der Medizinischen Universität zu Lübeck, Germany
,
Uwe Wiegand
1   From the Medizinische Klinik II der Medizinischen Universität zu Lübeck, Germany
,
Markus Kampmann
1   From the Medizinische Klinik II der Medizinischen Universität zu Lübeck, Germany
,
Hugo A. Katus
1   From the Medizinische Klinik II der Medizinischen Universität zu Lübeck, Germany
› Author Affiliations
Further Information

Publication History

Received 02 March 1999

Accepted after resubmission 01 October 1999

Publication Date:
11 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Objective

The present study sought to determine the incidence of increased procoagulant activity in patients with unstable angina (UAP), and to evaluate the relationship between cardiac troponin T (cTnT) and molecular markers of hemostatic activation.

Method

We studied 44 patients with UAP further classified by plasma cTnT levels. All patients received an antithrombotic therapy consisting of therapeutic doses of unfractionated heparin and acetylsalicylic acid. Quantitative levels of cTnT and plasma concentrations of fibrin monomers (FM), prothrombin fragments F1+2, thrombin antithrombin III complexes (TAT), plasminogen and α2-antiplasmin were sampled serially within the first 48 h.

Results

Increased plasma concentrations of FM were detected in 45.5% of patients and were more frequently present among those with cTnT concentrations >0.1 ng/ml (13 of 18 vs 7 of 26 patients, p = 0.003). In these patients, mean plasma concentrations of FM were significantly higher than in patients with cTnT <0.1 ng/ml (7.93 ± 2.3 vs 3.12 ± 0.6 µg/ml, p = 0.02). There was a close relationship between plasma levels of cTnT and FM (r = 0.74, p <0.004), prothrombin fragments F1+2 (r = 0.71, p = 0.046) and a trend to significance was noted for TAT (r = 0.42, p = 0.055). No significant correlation was observed with markers of the fibrinolytic system (plasminogen and α2-antiplasmin). Plasma levels of cTnT >0.1 ng/ml identified a concomitant increase of hemostatic markers with a sensitivity, specificity and positive predictive value of 65, 79, and 72% for FM, 63, 76, and 67% for prothrombin fragments F1+2, and 58, 66, and 39% for TAT, respectively.

Conclusions

In patients with UAP, cTnT identifies patients with increased procoagulant activity and is closely related to plasma levels of molecular markers of hemostatic activation. Therefore, cTnT alone or in combination with one of these markers may be helpful to identify patients requiring more potent antithrombin or antiplatelet therapy.

Key words

Unstable angina - troponin T - procoagulant activity - unfractionated heparin
 

  • References

  • 1 Theroux P, Fuster V. Acute coronary syndromes. Unstable angina and non- Q-wave myocardial infarction. Circulation 1998; 97: 1195-206.
    CrossrefPubMedGoogle Scholar
  • 2 Braunwald E. Unstable angina: a classification. Circulation 1989; 80: 410-4.
    CrossrefPubMedGoogle Scholar
  • 3 Katus HA, Remppis A, Neumann FJ, Scheffold T, Diederich KW, Vinar G, Noe A, Matern G, Kuebler W. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation 1991; 83: 902-12.
    CrossrefPubMedGoogle Scholar
  • 4 Hamm CW, Ravkilde J, Gerhardt W, Jorgensen P, Peheim E, Ljungdahl L, Goldmann B, Katus HA. The prognostic value of serum troponin T in unstable angina. N Engl J Med 1992; 327: 146-50.
    CrossrefPubMedGoogle Scholar
  • 5 Ohman EM, Armstrong PW, Christenson RH, Granger CB, Katus HA, Hamm CW, O´Hanesian MA, Wagner GS, Kleiman NS, Harrell FE, Califf RM, Topol EJ. for the GUSTO-IIA Investigators. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. N Engl J Med 1996; 335: 1333-41.
    CrossrefPubMedGoogle Scholar
  • 6 Ravkilde J, Horder M, Gerhardt W, Ljungdahl L, Pettersson T, Tryding N, Moller BH, Hamfelt A, Graven T, Asberg A. Diagnostic performance and prognostic value of serum troponin T in suspected acute myocardial infarction. Scand J Clin Lab Invest 1993; 53: 677-85.
    CrossrefPubMedGoogle Scholar
  • 7 Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC Study Group. Circulation 1996; 93: 1651-7.
    CrossrefPubMedGoogle Scholar
  • 8 Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group. J Am Coll Cardiol 1997; 29: 43-8.
    CrossrefPubMedGoogle Scholar
  • 9 Montalescot G, Philippe F, Ankri A, Vicaut E, Bearez E, Poulard JE, Carrie D, Flammang D, Dutoit A, Carayon A, Jardel C, Chevrot M, Bastard JP, Bigonzi F, Thomas D. for the French investigators of the ESSENCE Trial. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease. Circulation 1998; 98: 294-9.
    CrossrefPubMedGoogle Scholar
  • 10 Hamm CW, Heeschen C, Goldmann BU, Vahanian A, Adgey J, Miguel CM, Rutsch W, Berger J, Koostra J, Simoons ML. for the CAPTURE Study Investigators. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. N Engl J Med 1999; 340: 1623-9.
    CrossrefPubMedGoogle Scholar
  • 11 Report on the Joint International Society and Federation of Cardiology/ World Health Organization Task Force and Standardization of Clinical Nomenclature. Nomenclature and criteria for diagnosis of ischemic heart disease. Circulation 1979; 59: 607-8.
    CrossrefPubMedGoogle Scholar
  • 12 Galen RS. Predictive value of laboratory tests. Am J Cardiol 1975; 36: 536-8.
    PubMedGoogle Scholar
  • 13 Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys M, Maseri A. Prognostic value of C-reactive protein and serum amyloid A in severe unstable angina. N Engl J Med 1994; 331: 417-24.
    CrossrefPubMedGoogle Scholar
  • 14 Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997; 349: 462-6.
    CrossrefPubMedGoogle Scholar
  • 15 Rebuzzi AG, Quaranta G, Liuzzo G, Caligiuri G, Lanza GA, Gallimore R, Grillo RL, Cianflone D, Biasucci LM, Maseri A. Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris. Am J Cardiol 1998; 82: 715-9.
    CrossrefPubMedGoogle Scholar
  • 16 Toss H, Lindahl B, Siegbahn A, Wallentin L. for the FRISC Study Group. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. Circulation 1997; 96: 4204-10.
    CrossrefPubMedGoogle Scholar
  • 17 Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death: autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985; 71: 699-708.
    CrossrefPubMedGoogle Scholar
  • 18 Neri GGSerneri, Gensini GF, Carnovali M, Prisco D, Rogasi PG, Casolo GC, Fazi A, Abbate R. Association between time of increased fibrinopeptide A levels in plasma and episodes of spontaneous angina: a controlled prospective study. Am Heart J 1987; 113: 672-2.
    CrossrefPubMedGoogle Scholar
  • 19 Biasucci LM, Liuzzi G, Caliguri G, Quaranta G, Andreotti F, Sperti G, van de Greef W, Rebuzzi AG, Kluft C, Maseri A. Temporal relation between ischemic episodes and activation of the coagulation system in unstable angina. Circulation 1996; 93: 2121-7.
    CrossrefPubMedGoogle Scholar
  • 20 Merlini PA, Ardissino D, Bauer KA, Oltrona L, Pezzano A, Bottasso B, Rosenberg RD, Manucci PM. Persistent thrombin generation during heparin therapy in patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol 1997; 17: 1325-30.
    CrossrefPubMedGoogle Scholar
  • 21 Granger CB, Becker R, Tracy RP, Califf RM, Topol EJ, Pieper KS, Ross AM, Roth S, Lambrew C, Bovill EG. Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I trial. GUSTO-I Hemostasis Substudy Group. Global Utilization of Streptokinase and tPA for occluded coronary arteries. J Am Coll Cardiol 1998; 31: 497-505.
    CrossrefPubMedGoogle Scholar
  • 22 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.
    CrossrefPubMedGoogle Scholar
  • 23 Eisenberg PR, Kenzora JL, Sobel BE, Ludbrook PA, Jaffe AS. Relation between ST segment shifts during ischemia and thrombin activity in patients with unstable angina. J Am Coll Cardiol 1991; 18: 898-903.
    CrossrefPubMedGoogle Scholar
  • 24 Hirsh J, Fuster V. Guide to anticoagulation therapy, I: heparin. Circulation 1994; 89: 1449-68.
    CrossrefPubMedGoogle Scholar
  • 25 Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after discontinuation of heparin. N Engl J Med 1992; 327: 141-5.
    CrossrefPubMedGoogle Scholar
  • 26 Oltrona L, Eisenberg PR, Lasala JM, Sewall DJ, Shelton ME, Winters KJ. Association of heparin-resistent thrombin activity with acute ischemic complications of coronary interventions. Circulation 1996; 94: 2064-71.
    CrossrefPubMedGoogle Scholar
  • 27 Terres W, Kummel P, Sudrow A, Reuter H, Meinertz T, Hamm CW. Enhanced coagulation activation in troponin T-positive unstable angina pectoris. Am Heart J 1998; 135: 281-6.
    CrossrefPubMedGoogle Scholar
  • 28 Christenson RH, Azzazy HME. Biochemical markers of the acute coronary syndromes. Clin Chem 1998; 44: 1855-64.
    PubMedGoogle Scholar
  • 29 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombinantithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost 1988; 59: 105-6.
    PubMedGoogle Scholar
  • 30 Pelzer H, Schwarz A, Stuber W. Determination of human prothrombotic activation fragment 1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemost 1991; 65: 153-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Leroy-Matheron C, Gouault-Heilmann M. Influence of conditions of blood sampling on coagulation activation markers (prothrombin fragment 1 + 2, thrombin-antithrombin complexes and D-dimers) measurements. Thromb Res 1994; 74: 399-407.
    CrossrefPubMedGoogle Scholar
  • 32 Kapiotis S, Jilma B, Quehenberger P, Ruzicka K, Handler S, Speiser W. Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasminplasmin inhibitor complex. Circulation 1997; 96: 19-21.
    CrossrefPubMedGoogle Scholar
  • 33 Kienast J, Thompson SG, Raskino C, Pelzer H, Fechtrup C, Ostermann H, van de Loo J. Prothrombin activation fragment 1+2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis. Thromb Haemost 1993; 70: 550-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Giannitsis E, Siemens HJ, Mitusch R, Tettenborn I, Wiegand U, Schmücker G, Sheikhzadeh A, Stierle U. Prothrombin fragments F1+2, thrombin-antithrombin III complexes, fibrin monomers and fibrinogen in patients with coronary atherosclerosis. Int J Cardiol 1999; 68: 269-74.
    CrossrefPubMedGoogle Scholar
  • 35 Hamsten A, Wilman B, deFaire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63.
    CrossrefPubMedGoogle Scholar