**7. Management of IMiD-associated VTE**

No studies or guidelines are available to guide treatment of established thalidomide/lenalidomide-associated VTE. Although the use of LMWH has improved VTE management in patients with solid tumors [85], no similar experience has been built up in patients with MM. The recommended treatment for thalidomide- or lenalidomideassociated thrombosis is either LMWH or warfarin. However, the use of LMWH is more attractive because of the lack of need for laboratory monitoring and the reduced variability (compared with warfarin) caused by interference from drugs and food. Also, in patients with solid tumors, LMWH administered for 6 months after a first VTE episode (1 month at full dose and 5 months at approximately 75% of the full dose) has proved to be safe and superior to warfarin in preventing VTE recurrence [85]. However, the optimal duration of anticoagulation therapy in oncology patients remains controversial.

The optimal doses of the most commonly used LMWH are 100 U/kg every 12 h or 200 U/kg daily for dalteparin, 1 mg/kg every 12 h or 1.5 mg/kg daily for enoxaparin, and 86 U/kg every 12 h or 171 U/kg daily for nadroparin. In patients with a high risk of hemorrhage (thrombocytopenia or renal failure), association of monitoring of peak anti-factor Xa levels to maintain a range of 0.5 to 1.0 IU/mL could be very attractive. In addition, a reduction of 50% of the therapeutic dose of LMWH for platelet counts less than 50 x109/μL, and a temporary discontinuation of LMWH for platelet counts less than 20,000 x109/μL can be performed [86]. Also, UFH followed by warfarin remains a sensible alternative for VTE treatment in patients with CrCl <30 ml/min [87].

Zangari et al reported the treatment of 14 patients who developed thalidomide-related VTE. In 75% of them, administration of thalidomide was safely resumed after appropriate anticoagulation therapy was initiated. This consisted of low-molecular-weight heparin followed by warfarin, the target being the international normalized ratio of 2.5 to 3. Both anticoagulant and thalidomide treatments were continued as long as they were clinically indicated [88].

Alternative anti-myeloma treatment with an IMiS-free scheme should be seriously considered in patients who develop a VTE receiving LMWH or warfarin therapy with an appropriate INR [89]. However, if the use of IMiDs which produced the VTE is absolutely necessary, an alternative anticoagulant scheme could be used. In this setting, in patients with cancer-associated thrombosis while on warfarin therapy, with an appropriate INR, a recommended practice is to switch them to LMWH because it is more efficacious than warfarin [90]. On the other hand, dose escalation appears to be effective in patients who develop a cancer-associated thrombosis while on LMWH. In a small cohort study of oncology patients with recurrent thrombosis while on LMWH or warfarin, escalating the dose of LMWH by 20–25% or switching to LMWH, respectively, prevented further thrombotic episodes [91].
