Thrombosis research · 2013
Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Bharthuar Anubha, Khorana Alok A, Hutson Alan, Wang Jian-Guo, Key Nigel S, Mackman Nigel, Iyer Renuka V
Аннотация
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.
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.