Hemostatic changes after 1 month of thalidomide and dexamethasone therapy in patients with multiple myeloma

Abstract

Thromboembolic events (TEE) are a serious clinical problem in multiple myeloma (MM) patients receiving thalidomide (T). Thirty-one MM patients were tested on diagnosis and after 2 and 4 weeks of therapy with T alone, or T in combination with dexamethasone (TD). Closure time (CT) in PFA-100 and P-selectin expression were assessed, as well as plasma levels of thrombin-antithrombin complexes (TAT), D-dimer (DD), soluble thrombomodulin (sTM) and von Willebrand factor antigen (vWF:Ag), along with the activity of coagulation factor VII and factor VIII. The concentration of vascular endothelial growth factor and its type 1 and 2 receptors were also assayed. On diagnosis, significantly prolonged median CT with both used cartridges, elevated P-selectin expression, DD concentration, TAT, vWF:Ag and factor VIII and factor VII activity were seen in the patient group as compared to controls. Therapy with these regimens caused marked shortening of CT with both cartridges. Treatment with TD leads to the significant increase in CD62P expression on platelets. Median TAT value increased significantly in relation to baseline after therapy with both regimens. Factor VIII activity exceeded 150 % in all patients after 2 weeks of TD therapy and was markedly elevated compared to baseline. One month of TD therapy significantly increased sTM concentration. These results demonstrate the enhanced platelet and coagulation system activation already present in MM patients on diagnosis, which is further increased by antimyeloma therapy. These changes are more pronounced after TD therapy and may promote TEE. Tested angiogenesis marker levels are elevated already on diagnosis, do not change after therapy and have no significant impact on the coagulation system in patients with MM.

Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide‐based regimens

“…The role of thrombomodulin in the pathogenesis of VTE in MM remains unclear and there are conflicting data in the literature; in some studies , treatment with thalidomide may influence the levels of plasma‐soluble thombomodulin but this is not consistent . Other studies, as is the case in our study, have found increased soluble thrombomodulin levels in myeloma patients unrelated to thalidomide, which probably reflects the extent of MM or drug driven endothelial injury .…”

Effect of serum monoclonal protein concentration on haemostasis in patients with multiple myeloma

“…Fibrin polymerization induced by thrombin was impaired by paraprotein, which interacts with the g chain of Fbg [4]. In addition, some people found that light chain had lupus anticoagulant activity, which could be responsible for the correlation between TT and lightchain concentration [9]. Light-chain paraprotein might have a stronger nonspecific binding effect with Fbg and can affect TT more than other immunoglobulin types [8,10].…”

“…It could be that light-chain configuration is not suitable for blocking coagulation factors [20]. Severe thromboembolic events are rare at diagnosis of multiple myeloma [9,19,21]. D-dimer has a significantly higher mean in patients with multiple myeloma, which could indicate secondary hyperfibrinolysis in these patients, and there was a negative correlation between Fbg and M protein.…”

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

“…A hypercoagulable environment in MM is sustained by increased levels of inflammatory cytokines and other factors of coagulation. Fibrinolysis and fibrin polymerization is also disrupted due to interference by the monoclonal component [3,12,[36][37][38][39]54]. Platelet dysfunction and increased adhesion have been reported in patients with MM, which may also explain the demonstrated efficacy of aspirin as an agent for thromboprophylaxis in MM patients [38,40,41].…”

“…The rationale underlying the use of aspirin as thromboprophylaxis in low-risk MM patients who receive IMiDs lies with the evidence that supports enhanced platelet activation induced by IMiDs and altered platelet function in patients with MM [36,40,62,81]. Most clinicians chose the 100 mg dose, despite the lack of robust data to support it.…”