Baseline and treatment-related changes in thrombin generation in patients with multiple myeloma

Abstract

The prothrombotic risk in multiple myeloma (MM) could be potentially assessed by thrombin generation (TG) assays. TG was performed using Calibrated Automated Thrombography with 5 and 1 pM tissue factor. We compared baseline TG among 24 MM patients, 19 MGUS, and 50 healthy controls, and assessed change in TG in MM patients during the initial treatment period at 1, 2, and 3 months. MM subjects demonstrated increased FVIII and VWF:Ag levels pretreatment, and a prothrombotic TG phenotype with increased velocity index, reduced lag time and time-to-peak, and increased resistance to thrombomodulin inhibition. There were no significant changes in TG with treatment for the majority of parameters, however, MM subjects exhibited persistent elevation of velocity index throughout treatment. Two subjects developed thrombosis during the study period despite thromboprophylaxis. This study provides information on the optimal conditions for examining TG as a predictor of thrombotic risk in MM patients.

Keywords:

• Monoclonal gammopathy
• multiple myeloma
• thrombin generation
• venous thromboembolism
• hypercoagulability

Acknowledgements

The authors thank Dr Noemi Horvath (Consultant Haematologist, SA Pathology. Royal Adelaide Hospital) for contributing patients for the study; Reanu Gopal for assistance with the TG assays; Dr Stuart Howell (Statistician, University of Adelaide) for providing advice on statistical analysis; and all the participating volunteers and patients.

We are grateful for financial support from Mary Overton Award, Royal Adelaide Hospital Research Committee, South Australia.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1219900.