Variable resistance to plasminogen activator initiated fibrinolysis for intermediate-risk pulmonary embolism

William B. Stubblefield, Nathan Alves, Matthew T. Rondina, Jeffrey Kline

Research output: Contribution to journalArticle

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Abstract

Background: We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)- catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE). Methods: Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sexmatched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405). Results: Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT. Conclusion: The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT.

Original languageEnglish (US)
Article numbere0148747
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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Fibrin Clot Lysis Time
fibrinolysis
plasminogen activator
embolism
Carboxypeptidase B2
Plasminogen Activators
Fibrinolysis
Pulmonary Embolism
thrombin
Plasminogen Activator Inhibitor 1
lungs
Thrombelastography
t-plasminogen activator
Biomarkers
Tissue Plasminogen Activator
hemorrhage
biomarkers
Antifibrinolytic Agents
Plasminogen
Thromboplastin

ASJC Scopus subject areas

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

Cite this

Variable resistance to plasminogen activator initiated fibrinolysis for intermediate-risk pulmonary embolism. / Stubblefield, William B.; Alves, Nathan; Rondina, Matthew T.; Kline, Jeffrey.

In: PLoS One, Vol. 11, No. 2, e0148747, 01.02.2016.

Research output: Contribution to journalArticle

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abstract = "Background: We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)- catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE). Methods: Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sexmatched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50{\%} clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405). Results: Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95{\%} CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT. Conclusion: The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT.",
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