Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer

Vance G Nielsen, Ryan W. Matika, Michele L B Ley, Amy L Waer, Farid - Gharagozloo, Samuel S Kim, Valentine N Nfonsam, Evan S. Ong, Tun Jie, James A Warneke, Evangelina B. Steinbrenner

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Although cancer-mediated changes in hemostatic proteins unquestionably promote hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are less well defined. The goals of the present investigation were to determine if plasma obtained from patients with breast, lung, pancreas and colon cancer was less or more susceptible to lysis by tissue-type plasminogen activator (tPA) compared to plasma obtained from normal individuals. Archived plasma obtained from patients with breast (n=18), colon/pancreas (n=27) or lung (n=19) was compared to normal individual plasma (n=30) using a thrombelastographic assay that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples were activated with tissue factor/celite, had tPA added, and had data collected until clot lysis occurred. Additional, similar samples had potato carboxypeptidase inhibitor added to assess the role played by thrombin-activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than inflicting a hypofibrinolytic state, the three groups of cancers demonstrated increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of lysis, decreased clot lysis time). However, hypercoagulation manifested as increased speed of clot formation and strength compensated for enhanced fibrinolytic vulnerability, resulting in a clot residence time that was not different from normal individual thrombi. In sum, enhanced hypercoagulability associated with cancer was in part diminished by enhanced fibrinolytic vulnerability to tPA.

Original languageEnglish (US)
Pages (from-to)248-253
Number of pages6
JournalBlood Coagulation and Fibrinolysis
Volume25
Issue number3
DOIs
Publication statusPublished - 2014

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Keywords

  • Breast neoplasms
  • Colon neoplasms
  • Fibrinolysis
  • Lung neoplasms
  • Pancreas neoplasms
  • Plasminogen activators
  • Thrombelastography
  • Thrombin-activatable fibrinolysis inhibitor
  • Thrombophilia

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

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