Anti-t-PA antibodies in acute myocardial infarction after thrombolysis with rt-PA

Massimo Cugno, Roberto Castelli, Giuliana Bisiani, Samantha Griffini, Pier Luigi Meroni

Research output: Contribution to journalArticle

Abstract

Background: Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is successfully used in acute myocardial infarction with ST elevation (STEMI). Reocclusions follow rt-PA treatment in up to 30% of patients within one year. The infusion of rt-PA may induce the production of anti-t-PA antibodies which could interfere with the function of the native t-PA molecule. Methods: In order to detect and characterise anti-t-PA antibodies, plasma samples were collected from 30 STEMI patients (20 treated and 10 not treated with rt-PA) at baseline before rt-PA infusion and then 15, 30, 90 and 180 days after STEMI and from 40 healthy subjects at baseline only. Immunoenzymatic, chromatographic and chromogenic methods were employed. Results: An increase of anti-t-PA antibodies was observed 15 days (IgM, p = 0.0001) and 30 days (IgG, p = 0.0001) after rt-PA infusion. Six patients had large increases of anti-t-PA IgG which bound the catalytic domain of t-PA (two cases) or kringle 2 domain (four cases), were of IgG1 or IgG3 subclasses and interacted with the t-PA molecule in fluid phase. Conclusion: The infusion of rt-PA may induce the production of specific antibodies that bind active sites of t-PA, thus potentially reducing its in vivo function.

Original languageEnglish
Pages (from-to)25-29
Number of pages5
JournalEuropean Journal of Internal Medicine
Volume21
Issue number1
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Tissue Plasminogen Activator
Myocardial Infarction
Antibodies
Immunoglobulin G
Catalytic Domain
Kringles
Antibody Formation
Immunoglobulin M
Healthy Volunteers
ST Elevation Myocardial Infarction

Keywords

  • Acute myocardial infarction
  • Antibodies
  • Reocclusion
  • Tissue-type plasminogen activator

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Anti-t-PA antibodies in acute myocardial infarction after thrombolysis with rt-PA. / Cugno, Massimo; Castelli, Roberto; Bisiani, Giuliana; Griffini, Samantha; Meroni, Pier Luigi.

In: European Journal of Internal Medicine, Vol. 21, No. 1, 02.2010, p. 25-29.

Research output: Contribution to journalArticle

Cugno, Massimo ; Castelli, Roberto ; Bisiani, Giuliana ; Griffini, Samantha ; Meroni, Pier Luigi. / Anti-t-PA antibodies in acute myocardial infarction after thrombolysis with rt-PA. In: European Journal of Internal Medicine. 2010 ; Vol. 21, No. 1. pp. 25-29.
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abstract = "Background: Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is successfully used in acute myocardial infarction with ST elevation (STEMI). Reocclusions follow rt-PA treatment in up to 30{\%} of patients within one year. The infusion of rt-PA may induce the production of anti-t-PA antibodies which could interfere with the function of the native t-PA molecule. Methods: In order to detect and characterise anti-t-PA antibodies, plasma samples were collected from 30 STEMI patients (20 treated and 10 not treated with rt-PA) at baseline before rt-PA infusion and then 15, 30, 90 and 180 days after STEMI and from 40 healthy subjects at baseline only. Immunoenzymatic, chromatographic and chromogenic methods were employed. Results: An increase of anti-t-PA antibodies was observed 15 days (IgM, p = 0.0001) and 30 days (IgG, p = 0.0001) after rt-PA infusion. Six patients had large increases of anti-t-PA IgG which bound the catalytic domain of t-PA (two cases) or kringle 2 domain (four cases), were of IgG1 or IgG3 subclasses and interacted with the t-PA molecule in fluid phase. Conclusion: The infusion of rt-PA may induce the production of specific antibodies that bind active sites of t-PA, thus potentially reducing its in vivo function.",
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AB - Background: Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is successfully used in acute myocardial infarction with ST elevation (STEMI). Reocclusions follow rt-PA treatment in up to 30% of patients within one year. The infusion of rt-PA may induce the production of anti-t-PA antibodies which could interfere with the function of the native t-PA molecule. Methods: In order to detect and characterise anti-t-PA antibodies, plasma samples were collected from 30 STEMI patients (20 treated and 10 not treated with rt-PA) at baseline before rt-PA infusion and then 15, 30, 90 and 180 days after STEMI and from 40 healthy subjects at baseline only. Immunoenzymatic, chromatographic and chromogenic methods were employed. Results: An increase of anti-t-PA antibodies was observed 15 days (IgM, p = 0.0001) and 30 days (IgG, p = 0.0001) after rt-PA infusion. Six patients had large increases of anti-t-PA IgG which bound the catalytic domain of t-PA (two cases) or kringle 2 domain (four cases), were of IgG1 or IgG3 subclasses and interacted with the t-PA molecule in fluid phase. Conclusion: The infusion of rt-PA may induce the production of specific antibodies that bind active sites of t-PA, thus potentially reducing its in vivo function.

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