Tissue factor-bearing extracellular vesicles, procoagulant phospholipids and D-dimer as potential biomarkers for venous thromboembolism in patients with newly diagnosed multiple myeloma: A comprehensive analysis

Abstract

Background

Candidate biomarkers to improve venous thromboembolism (VTE) risk prediction in patients with newly diagnosed multiple myeloma (MM) undergoing anti-myeloma therapy include tissue factor-bearing microvesicles (MV-TF), procoagulant phospholipids (procoag-PPL), and D-dimer.

Objective

We aimed to determine the levels of MV-TF, procoag-PPL, and D-dimer at baseline and during initial anti-myeloma therapy and their association with the risk of VTE.

Methods

This prospective, longitudinal, observational study included 71 patients with newly diagnosed MM who were eligible for anti-myeloma therapy. Circulating MV-TF levels were measured using a functional method adapted from the Chapel Hill TF-dependent Factor Xa generation assay, and PPL and D-dimer levels with commercially available assays. The three biomarkers were measured at baseline and throughout treatment.

Results

Baseline and on-treatment MV-TF levels were higher in patients who developed VTE compared to those who did not (4.25 versus 2.75 fM at baseline, p = 0.047 and 6.5 versus 1.5 fM during treatment, p = 0.001). Baseline and on-treatment Procoag-PPL clotting times did not differ between the groups. Baseline D-dimer levels tended to be higher in patients who developed VTE than in those who did not (1.38 versus 0.7 μg/mL, p = 0.08). During treatment, D-dimer levels were significantly higher in the VTE group than in the non-VTE group (1.08 versus 0.44 μg/mL, p = 0.008).

Conclusion

Our results suggest that MV-TF and D-dimer levels may help to refine VTE risk prediction in nMM patients undergoing anti-myeloma therapy. Adequately sized studies including patients receiving new MM therapies are needed to confirm this hypothesis.