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Thromb Haemost 2009; 101(04): 734-740
DOI: 10.1160/TH08-06-0407
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Microparticle-linked tissue factor activity and increased thrombin activity play a potential role in fibrinolysis failure in ST-segment elevation myocardial infarction

Marie-Geneviève Huisse
1   Department of Haematology, AP-HP, Hôpital Bichat, Paris, France
3   CIB PhenoGen, University Paris 7-Denis Diderot, Paris, France
4   INSERM U698; University Paris 7-Denis Diderot, Paris, France
,
Nadine Ajzenberg
1   Department of Haematology, AP-HP, Hôpital Bichat, Paris, France
3   CIB PhenoGen, University Paris 7-Denis Diderot, Paris, France
4   INSERM U698; University Paris 7-Denis Diderot, Paris, France
,
Laurent Feldman
2   Department of Cardiology, AP-HP, Hôpital Bichat, Paris, France
4   INSERM U698; University Paris 7-Denis Diderot, Paris, France
,
Marie-Claude Guillin
1   Department of Haematology, AP-HP, Hôpital Bichat, Paris, France
3   CIB PhenoGen, University Paris 7-Denis Diderot, Paris, France
4   INSERM U698; University Paris 7-Denis Diderot, Paris, France
,
Philippe Gabriel Steg
2   Department of Cardiology, AP-HP, Hôpital Bichat, Paris, France
4   INSERM U698; University Paris 7-Denis Diderot, Paris, France
› Author Affiliations Financial support: This work was supported by funds from Fondation de France. Additional support was provided by Diagnostica Stago.
Further Information

Publication History

Received: 24 June 2008

Accepted after major revision: 05 January 2009

Publication Date:
23 November 2017 (online)

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Summary

Fibrinolysis for acute ST-segment elevation MI achieves early recanalisation of the infarct artery in approximately 60% of cases. The aim of the study was to determine whether failure to achieve recanalisation was associated with differences in haemostasis biomarkers compared to patients with successful fibrinolysis. Fourty-three patients were prospectively enrolled in a case-control study. All patients had received tenecteplase (TNKtPA) together with aspirin (500 mg) and heparin (5,000 IU). Emergency angiography within 90 minutes of bolus TNK-tPA identified 13 TIMI 0–2 patients (cases) and 30 TIMI 3 patients (controls). Blood samples were collected before angiography to determine tissue factor activity associated with microparticles (TF-MP); soluble platelet glycoprotein V (sGPV) and thrombinantithrombin complexes (TAT) as markers of thrombin generation; tissue plasminogen activator (endogenous tPA+ TNKtPA), plasminogen activator inhibitor (PAI-1) and plasmin-anti-plasmin complexes (PAP) as markers of plasmin generation. The baseline characteristics of the two patients’ groups were similar with respect to sex, age, and risks factors. Cases differed from controls by higher TF-MP levels (1.9 [1–13] vs. 1 [0.6–1.3] pM), sGPV (67 [51–126] vs. (48 [39–72] ng/ml), p=0.039 and TAT (10 [4–37.5] vs. 4 [2.9–7.2] ng/ml), p=0.035. TAT correlated with TF-MP (r=0.51, p=0.0064) and sGPV (r=0.51, p=0.0018). No significant difference was observed in tPA or PAI-1 levels. PAP were lower in cases (18.83 [14.83–40.43] μg/ml) than in controls (35.83 [27.9–43.94] μg/ml), p=0.045. In conclusion, fibrinolysis failure in AMI is characterised by a higher procoagulant state associated with TF-MP and a lower plasmin generation.

Keywords

Myocardial infarction - fibrinolysis - thrombin - microparticle-linked tissue factor
 

  • References

  • 1 Boden WE, Eagle K, Granger CB. Reperfusion strategies in acute ST-segment elevation myocardial infarction: a comprehensive review of contemporary management options. J Am Coll Cardiol 2007; 50: 917-929.
    CrossrefPubMedGoogle Scholar
  • 2 Nordt TK, Bode C. Thrombolysis: newer thrombolytic agents and their role in clinical medicine. Heart 2003; 89: 1358-1362.
    CrossrefPubMedGoogle Scholar
  • 3 Cannon CP. Overcoming thrombolytic resistance: rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction. J Am Coll Cardiol 1999; 34: 1395-1402.
    CrossrefPubMedGoogle Scholar
  • 4 LeBreton H, Topol E, Plow EF. Evidence for a pivotal role of platelets in vascular reocclusion and restenosis. Cardiovasc Res 1996; 31: 235-236.
    CrossrefPubMedGoogle Scholar
  • 5 Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation 2005; 111: 3481-3488.
    CrossrefPubMedGoogle Scholar
  • 6 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-843.
    CrossrefPubMedGoogle Scholar
  • 7 Sakharov DV, Plow EF, Rijken DC. On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B. J Biol Chem 1997; 272: 14477-14482.
    CrossrefPubMedGoogle Scholar
  • 8 Huber K. Plasminogen activator inhibitor type-1 (part two): role for failure of thrombolytic therapy. PAI-1 resistance as a potential benefit for new fibrinolytic agents. J Thromb Thrombolysis 2001; 11: 195-202.
    CrossrefPubMedGoogle Scholar
  • 9 Fernandez-Cadenas I, Alvarez-Sabin J, Ribo M. et al. Influence of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 gene polymorphisms on tissue-type plasminogen activator-induced recanalization in ischemic stroke patients. J Thromb Haemost 2007; 5: 1862-1868.
    CrossrefPubMedGoogle Scholar
  • 10 Scharfstein JS, Abendschein DR, Eisenberg PR. et al. Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. TIMI-5 Investigators. Thrombolysis in Myocardial Infarction. Am J Cardiol 1996; 78: 503-510.
    CrossrefPubMedGoogle Scholar
  • 11 Owen J, Friedman KD, Grossman BA. et al. Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity. Blood 1988; 72: 616-620.
    PubMedGoogle Scholar
  • 12 Merlini PA, Cugno M, Rossi ML. et al. Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction. Am J Cardiol 2004; 93: 822-825.
    CrossrefPubMedGoogle Scholar
  • 13 Hoffmeister HM, Szabo S, Kastner C. et al. Thrombolytic therapy in acute myocardial infarction: comparison of procoagulant effects of streptokinase and alteplase regimens with focus on the kallikrein system and plasmin. Circulation 1998; 98: 2527-2533.
    CrossrefPubMedGoogle Scholar
  • 14 Paganelli F, Alessi MC, Morange P. et al. Relationship of plasminogen activator inhibitor-1 levels following thrombolytic therapy with rt-PA as compared to streptokinase and patency of infarct related coronary artery. Thromb Haemost 1999; 82: 104-108.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Serebruany VL, Malinin AI, Callahan KP. et al. Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet sub-study. Am Heart J 2003; 145: 636-642.
    CrossrefPubMedGoogle Scholar
  • 16 Szabo S, Letsch R, Ehlers R. et al. Absence of paradoxical thrombin activation by fibrin-specific thrombolytics in acute myocardial infarction: comparison of single-bolus tenecteplase and front-loaded alteplase. Thromb Res 2002; 106: 113-119.
    CrossrefPubMedGoogle Scholar
  • 17 Juliard JM, Himbert D, Cristofini P. et al. A matched comparison of the combination of prehospital thrombolysis and standby rescue angioplasty with primary angioplasty. Am J Cardiol 1999; 83: 305-310.
    CrossrefPubMedGoogle Scholar
  • 18 Juliard JM, Himbert D, Golmard JL. et al. Can we provide reperfusion therapy to all unselected patients admitted with acute myocardial infarction?. J Am Coll Cardiol 1997; 30: 157-164.
    CrossrefPubMedGoogle Scholar
  • 19 Nieuwland R, Berckmans RJ, McGregor S. et al. Cellular origin and procoagulant properties of micro-particles in meningococcal sepsis. Blood 2000; 95: 930-935.
    PubMedGoogle Scholar
  • 20 Aleil B, Meyer N, Wolff V. et al. Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies. Thromb Haemost 2006; 96: 505-511.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Modi NB, Fox NL, Clow FW. et al. Pharmacokinetics and pharmacodynamics of tenecteplase: results from a phase II study in patients with acute myocardial infarction. J Clin Pharmacol 2000; 40: 508-515.
    CrossrefPubMedGoogle Scholar
  • 22 Bonderman D, Teml A, Jakowitsch J. et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood 2002; 99: 2794-2800.
    CrossrefPubMedGoogle Scholar
  • 23 Ott I, Malcouvier V, Schomig A. et al. Proteolysis of tissue factor pathway inhibitor-1 by thrombolysis in acute myocardial infarction. Circulation 2002; 105: 279-281.
    CrossrefPubMedGoogle Scholar
  • 24 Steppich B, Mattisek C, Sobczyk D. et al. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction. Thromb Haemost 2005; 93: 35-39.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Ravanat C, Freund M, Mangin P. et al. GPV is a marker of in vivo platelet activation--study in a rat thrombosis model. Thromb Haemost 2000; 83: 327-333.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Azorsa DO, Moog S, Ravanat C. et al. Measurement of GPV released by activated platelets using a sensitive immunocapture ELISA--its use to follow platelet storage in transfusion. Thromb Haemost 1999; 81: 131-138.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Aleil B, Mossard JM, Wiesel ML. et al. Increased plasma levels of soluble platelet glycoprotein V in patients with acute myocardial infarction. J Thromb Haemost 2003; 1: 1846-1847.
    CrossrefPubMedGoogle Scholar
  • 28 Morel O, Hugel B, Jesel L. et al. Circulating procoagulant microparticles and soluble GPV in myocardial infarction treated by primary percutaneous transluminal coronary angioplasty. A possible role for GPIIb-IIIa antagonists. J Thromb Haemost 2004; 2: 1118-1126.
    CrossrefPubMedGoogle Scholar
  • 29 Huisse MG, Lanoy E, Tcheche D. et al. Prothrombotic markers and early spontaneous recanalization in ST-segment elevation myocardial infarction. Thromb Haemost 2007; 98: 420-426.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Rabie T, Strehl A, Ludwig A. et al. Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V. J Biol Chem 2005; 280: 14462-14468.
    CrossrefPubMedGoogle Scholar
  • 31 Rauch U, Bonderman D, Bohrmann B. et al. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: 170-175.
    PubMedGoogle Scholar
  • 32 Schwertz H, Tolley ND, Foulks JM. et al. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J Exp Med 2006; 203: 2433-2440.
    CrossrefPubMedGoogle Scholar
  • 33 Collet JP, Montalescot G, Lesty C. et al. A structural and dynamic investigation of the facilitating effect of glycoprotein IIb/IIIa inhibitors in dissolving platelet-rich clots. Circ Res 2002; 90: 428-434.
    CrossrefPubMedGoogle Scholar
  • 34 Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension 2006; 48: 180-186.
    CrossrefPubMedGoogle Scholar
  • 35 Tanswell P, Modi N, Combs D. et al. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet 2002; 41: 1229-1245.
    CrossrefPubMedGoogle Scholar
  • 36 Zalewski J, Undas A, Godlewski J. et al. No-reflow phenomenon after acute myocardial infarction is associated with reduced clot permeability and susceptibility to lysis. Arterioscler Thromb Vasc Biol 2007; 27: 2258-2265.
    CrossrefPubMedGoogle Scholar
  • 37 Colucci M, DșAprile AM, Italia A, Gresele P, Morser J, Semeraro N. Thrombin activatable fibrinolysis inhibitor (TAFI) does not inhibit in vitro thrombolysis by pharmacological concentrations of t-PA. Thromb Haemost 2001; 85: 661-666.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Sabatine MS, Cannon CP, Gibson CM. et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005; 352: 1179-1189.
    CrossrefPubMedGoogle Scholar
  • 39 Chen ZM, Jiang LX, Chen YP. et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366: 1607-1621.
    CrossrefPubMedGoogle Scholar
  • 40 Varin R, Mirshahi S, Mirshahi P. et al. Clot structure modification by fondaparinux and consequence on fibrinolysis: a new mechanism of antithrombotic activity. Thromb Haemost 2007; 97: 27-31.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Peters RJ, Joyner C, Bassand JP. et al. The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial. Eur Heart J 2008; 29: 324-331.
    CrossrefPubMedGoogle Scholar
  • 42 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.
    CrossrefPubMedGoogle Scholar