Immunomodulatory drugs increase endothelial tissue factor expression in vitro

Area of Science:

• Hematology
• Oncology
• Vascular Biology

Background:

• Immunomodulatory drugs like thalidomide (THL) and lenalidomide (LEN) are used for multiple myeloma.
• These drugs can cause venous thromboembolism, a serious complication in myeloma patients.
• The best strategy for preventing drug-induced hypercoagulability is unclear.

Purpose of the Study:

• To investigate how THL and LEN affect endothelial cell tissue factor (TF) expression and function.
• To understand the regulation of TF activity induced by these drugs.
• To assess the in vitro efficacy of low molecular weight heparin and aspirin in modulating TF activity.

Main Methods:

• Utilized an in vitro model with human umbilical vein endothelial cells.
• Assessed TF activity and antigen levels.
• Employed flow cytometry, real-time PCR, and electron microscopy.

Main Results:

• THL and LEN significantly increased TF activity, mRNA, and cell-surface antigen in endothelial cells, especially with tumor necrosis factor-α (TNFα).
• Endothelial cell-derived microparticles expressing TF activity were generated in the presence of TNFα.
• Dalteparin and anti-TF antibodies strongly inhibited TF activity, while aspirin showed only moderate inhibition.

Conclusions:

• In vitro findings support the hypothesis that THL and LEN induce a hypercoagulable state.
• This hypercoagulability is mediated by increased endothelial TF expression.
• These results have implications for thromboprophylaxis strategies in myeloma patients treated with immunomodulatory drugs.