Tissue factor-bearing microparticles and CA19.9: Two players in pancreatic cancer-Associated thrombosis¿

Abstract

Background: Cancer-related venous thromboembolism (VTE) heralds a poor prognosis, especially in pancreatic adenocarcinoma (PAC). Tissue factor (TF) is implicated as one of the main culprits in PAC-Associated VTE and disease progression. Methods: In a prospective cohort study of 79 PAC patients, we measured plasma CA19-9 and microparticle-Associated TF activity (MP-TF activity). In addition, we enumerated TF + MPs and MUC1 + MPs in plasma (n=55), and studied the expression of TF, MUC1, CD31 and CD68 in tumour tissue (n=44). Results: Plasma MP-TF activity was markedly elevated in PAC patients with VTE compared with those without (median: 1925 vs 113 fM Xa min -1; P<0.001) and correlated with the extent of thromboembolic events, metastatic disease and short survival. Similar results were found for CA19-9. Patients with massively progressing thrombosis and cerebral embolisms despite anticoagulant therapy (n=3) had the highest MP-TF activities (12 118-40 188 fM Xa min -1) and CA19-9 (40 730-197 000 kU l -1). All tumours expressed MUC1 and TF. MP-TF activity did not correlate with intensity of TF expression in adenocarcinoma cells, but corresponded with numbers of TF + macrophages in the surrounding stroma. Conclusions: Circulating TF + MPs and mucins may concertedly aggravate coagulopathy in PAC. Understanding of underlying mechanisms may result in new treatment strategies for VTE prevention and improvement of survival.