Microparticle tissue factor activity is increased in cancer patients prior to the development of venous thromboembolism

Introduction: Cancer greatly increases the risk of venous thromboem-bolism (VTE). Here, we investigated the contribution of microparti-cle-dependent procoagulant activity to the prothrombotic state in these patients. Methods: In 43 cancer patients without VTE at entry and 22 healthy volunteers, markers of in vivo and microparticle-dependent coagulation were measured and patients were prospectively followed for 6 months for the development of VTE. Procoagulant activity of microparticles (MPs) was measured using a phospholipid dependent test (STA Procoag PLL), a factor Xa-generation assay (Xa-assay) with and without anti-tissue factor (TF), and a fibrin generation test (FGT) with and without anti-factor VII(a). Results: Markers of in vivo coagulation activation and total number of circulating MPs were elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/L, D-dimer 0.76 vs. 0.22 mg/L and 5.53 x 106 vs. 3.37 x 106 microparticles per mL; all P <0.001). Five cancer patients (12%) developed VTE during follow-up. Patients with VTE had comparable levels of coagulation activation markers and phos-pholipid dependent MP procoagulant activity. However, TF-mediated Xa-generation (0.82 vs. 0.21 pg/mL, P = 0.016) and the VIIa-dependent FGT (13% vs. 0%, P = 0.036) were higher in the VTE group compared with the non-VTE group.