Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction

Tullio Palmerini, Luciana Tomasi, Chiara Barozzi, Diego Della Riva, Andrea Mariani, Nevio Taglieri, Ornella Leone, Claudio Ceccarelli, Stefano De Servi, Angelo Branzi, Philippe Genereux, Gregg W. Stone, Jasimuddin Ahamed

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Abstract

Introduction: Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention. Methods: Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients. Results: Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities. Conclusions: Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis.

Original languageEnglish (US)
Article numbere81501
JournalPLoS ONE
Volume8
Issue number12
DOIs
StatePublished - Dec 11 2013

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myocardial infarction
Thromboplastin
coronary vessels
Coagulation
coagulation
Coronary Vessels
Thrombosis
antigens
Antigens
Percutaneous Coronary Intervention
cell aggregates
Staining and Labeling
Platelets
Immunoprecipitation
Blood Platelets
Paraffin Embedding
ST Elevation Myocardial Infarction
tissues
Coronary Thrombosis
Coagulants

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Palmerini, Tullio ; Tomasi, Luciana ; Barozzi, Chiara ; Della Riva, Diego ; Mariani, Andrea ; Taglieri, Nevio ; Leone, Ornella ; Ceccarelli, Claudio ; De Servi, Stefano ; Branzi, Angelo ; Genereux, Philippe ; Stone, Gregg W. ; Ahamed, Jasimuddin. / Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction. In: PLoS ONE. 2013 ; Vol. 8, No. 12.
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title = "Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction",
abstract = "Introduction: Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention. Methods: Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients. Results: Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities. Conclusions: Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis.",
author = "Tullio Palmerini and Luciana Tomasi and Chiara Barozzi and {Della Riva}, Diego and Andrea Mariani and Nevio Taglieri and Ornella Leone and Claudio Ceccarelli and {De Servi}, Stefano and Angelo Branzi and Philippe Genereux and Stone, {Gregg W.} and Jasimuddin Ahamed",
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Palmerini, T, Tomasi, L, Barozzi, C, Della Riva, D, Mariani, A, Taglieri, N, Leone, O, Ceccarelli, C, De Servi, S, Branzi, A, Genereux, P, Stone, GW & Ahamed, J 2013, 'Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction', PLoS ONE, vol. 8, no. 12, e81501. https://doi.org/10.1371/journal.pone.0081501

Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction. / Palmerini, Tullio; Tomasi, Luciana; Barozzi, Chiara; Della Riva, Diego; Mariani, Andrea; Taglieri, Nevio; Leone, Ornella; Ceccarelli, Claudio; De Servi, Stefano; Branzi, Angelo; Genereux, Philippe; Stone, Gregg W.; Ahamed, Jasimuddin.

In: PLoS ONE, Vol. 8, No. 12, e81501, 11.12.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction

AU - Palmerini, Tullio

AU - Tomasi, Luciana

AU - Barozzi, Chiara

AU - Della Riva, Diego

AU - Mariani, Andrea

AU - Taglieri, Nevio

AU - Leone, Ornella

AU - Ceccarelli, Claudio

AU - De Servi, Stefano

AU - Branzi, Angelo

AU - Genereux, Philippe

AU - Stone, Gregg W.

AU - Ahamed, Jasimuddin

PY - 2013/12/11

Y1 - 2013/12/11

N2 - Introduction: Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention. Methods: Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients. Results: Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities. Conclusions: Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis.

AB - Introduction: Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention. Methods: Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients. Results: Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities. Conclusions: Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis.

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