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.