Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers.

Abstract

BACKGROUND:

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

PATIENTS AND METHODS:

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

RESULTS:

The study population comprised 117 patients, including pancreatic (n=80), biliary (n=34) or unknown primary histologically consistent with PBC (n=3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n=15), deep venous thrombosis (n=21) and other arterial or venous events (n=32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity<2.5 pg/mL (p<0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

CONCLUSIONS:

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.

• Authors: Anubha Bharthuar, Alok A Khorana, Alan Hutson, Jian-Guo Wang, Nigel S Key, Nigel Mackman, Renuka V Iyer
• Journal: Thrombosis research (Thromb Res) Vol. 132 Issue 2 Pg. 180-4 (Aug 2013) ISSN: 1879-2472 [Electronic] United States
• PMID: 23856554 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Thromboplastin

Topics

• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms (blood)
• Bile Ducts, Intrahepatic
• Cell-Derived Microparticles (metabolism)
• Cohort Studies
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (blood)
• Prognosis
• Survival Analysis
• Thromboembolism (blood, pathology)
• Thromboplastin (metabolism)