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

TitleTissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer.
Publication TypeJournal Article
Year of Publication2014
AuthorsNielsen VG, Matika RW, Ley MLB, Waer AL, Gharagozloo F, Kim S, Nfonsam VN, Ong ES, Jie T, Warneke JA, Steinbrenner EB
JournalBlood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
Volume25
Issue3
Pagination248-53
Date Published2014 Apr
ISSN1473-5733
KeywordsAdult, Breast Neoplasms, Colonic Neoplasms, Female, Fibrinolysis, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasms, Pancreatic Neoplasms, Tissue Plasminogen Activator, Young Adult
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.

DOI10.1097/MBC.0000000000000040
Alternate JournalBlood Coagul. Fibrinolysis