Microparticle-Associated Tissue Factor Activity and Venous Thrombosis in Multiple Myeloma.

Abstract

Background: Multiple myeloma (MM) is associated with an increased risk of venous thrombo-embolic complications. The pathogenesis of venous thromboembolism (VTE) in MM is not yet clarified. Recently an association between microparticle-associated tissue factor (MP-TF) activity in plasma and thrombosis in patients with adenocarcinoma has been reported. Aim of this study was to measure MP-TF activity in patients with MM before and after treatment with chemotherapy and to investigate whether MP-TF activity is associated with VTE in these patients.Patients and results: MP-TF activity was assessed in 123 patients with newly diagnosed multiple myeloma who were eligible for combination chemotherapy and in 20 healthy volunteers. MP-TF activity levels were higher in untreated MM patients compared to the healthy volunteers (17.8 fM Xa/min [8.8–32.8] (median [Inter Quartile Range] versus 4.7 fM Xa/min [2.3–6.6], p<0.001). After three courses of chemotherapy the level of MP-TF activity had decreased significantly to 11.8 fM Xa/min [7.0–18.3], but were still higher than in controls (P<0.001). VTE occurred in 12 patients (10%). In MM patients with VTE the level of MP-TF activity remained elevated after induction chemotherapy (17.9 [9.3– 36.3]), in contrast to MM patients not developing VTE (11.1 [6.9–16.6] ). MP-TF levels after chemotherapy were significantly associated with the risk of VTE, with a 4% increase of VTE risk for every fM Xa/ min MP-TF activity increase (95% CI: 1–8%, p=0.03)Conclusion: MP-TF activity levels in plasma are increased in patients with multiple myeloma and they decrease significantly after induction chemotherapy. Persistent high MP-TF activity is observed in patients who developed VTE during the induction phase chemotherapy, and is associated with VTE risk. Our findings suggest that MP-TF activity levels may have a pathogenetic role in VTE in multiple myeloma patients.