Procoagulant mechanisms of chemotherapy in multiple myeloma

• Research type

  Research Study

• Full title

  Study of apoptosis related changes and endothelial responses of multiple myeloma patients treated with chemotherapy.

• IRAS ID

  74471

• Contact name

  Anthony Maraveyas

• Sponsor organisation

  Research & Development Department, Hull & East Yorkshire Hospitals NHS Trust

• Eudract number

  2012-001813-17

• ISRCTN Number

  n/a

• Research summary

  The incidence of venous thromboembolism (VTE)is increased in cancer patients, and estimated at 3% in patients with multiple myeloma (MM). The use of certain anti-cancer drugs is known to induce changes in the blood signifying a greater likelihood of developing thrombosis (blood clots). The incidence of VTE in patients with MM can increase up to 26% with the use of new chemotherapeutic drug combinations. Thalidomide (Thal), lenalidomide (Len) and bortezomib (Btz) are used in the treatment of MM, which have significantly improved survival in these patients. Thal and Len have been shown to increase the risk of VTE by an unknown mechanism. VTE prophylaxis strategies, such as low molecular weight heparin (LMWH) have been shown to prevent this risk. Whereas, Btz, is not associated with an increased risk of VTE. Chemotherapy-induced changes, such as apoptosis (programmed cell death) generates microparticles (MPs) containing tissue factor (TF) and membrane phospholipids leading to procoagulant activity (PCA), which could be involved in this mechanism. TF is the primary initiator of the clotting cascade, which has been shown to be increased in certain types of cancer. However, not much is known about the role of TF in MM. This study will investigate the following in patients with MM (newly diagnosed and relapsed): ?½ The quantity of MPs containing TF, endothelial-derived MPs and platelet-derived MPs. ?½ The PCA of platelet-poor plasma ?½ Endothelial function ?½ Platelet function The principle aim of the study is to examine the disruption of the endothelium (vessel lining), platelets and the clotting cascade caused by the novel chemotherapeutic combinations used for the treatment of MM. Understanding the impact of treatment on the thrombotic risk of these patients is of vital importance to allow a more superior strategy for their thromboprophylaxis. Furthermore, the results of this study may identify therapeutic targets for future research.

• REC name

  Yorkshire & The Humber - Leeds East Research Ethics Committee

• REC reference

  12/YH/0328

• Date of REC Opinion

  6 Aug 2012

• REC opinion

  Further Information Favourable Opinion