1. Complicanze trombotiche nel mieloma multiplo Mauro Berrettini S.C. Medicina Generale-DH Oncologico Ospedale di Orvieto Mediterranean School of Oncology Orvieto 22 Novembre 2009

2. Hemostasis-related complications in plasma cell dyscrasias thrombocytopenia endothelial damage acquired von Willebrand disease acquired APC resistance heparin-like anticoagulants hypofibrinolisis clotting factor deficiencies increased F.VIII/vWF amyloidosis lupus anticoagualant Bleeding Thrombosis

3. Incidence of deep vein thrombosis (DVT) in monoclonal gammopathy (MGUS) and multiple myeloma(MM) US VA hospital records (1980-1996) Incidence R.R 1000 pt/years General (4.196.197) 0.9 MGUS (2374) 3.1 3.3 MM ( 6192) 8.7 9.2 Kristinsson S.Y.et al, Blood 2008;112:3582-86

4. MGUS MM C Kristinsson SY et al., Blood 2008,112:3582-86

5. High variability due: Age History venous thromboembolism(VTE) Stage of the disease Hypercoagulability Immobilization CVC Comorbidities Therapy: chemotherapies, immunomodulatory drugs (thalidomide,lenalidomide) Incidence of deep vein thrombosis (DVT) in monoclonal gammopathy (MGUS) and multiple myeloma(MM)

6. Eby C., British Journal of Haematology, 2009; 145, 151-163

7. Meta-analysis of the incidence of venous thromboembolic events with induction thalidomide Hicks L.K. et al.,, Cancer Treatment Rewies,2008; 34:442-452

8. Meta-analysis of the incidence of venous thromboembolic events with maintenance thalidomide Hicks L.K. et al.,, Cancer Treatment Rewies,2008; 34:442-452

9. Clinical studies of thromboprophylaxis in MM patients receiving thalidomide or lenalidomide Falanga A, Marchetti M., J.Clin.Onc.2009;27:4848-57

10. Meta-analysis of the incidence of venous thromboembolic events with induction thalidomide Hicks L.K. et al.,, Cancer Treatment Rewies,2008; 34:442-452

11. Prevention of venous thromboembolism (VTE) in MM “In the absence of clear data from randomized studies,….. …..proposed strategies are the result of common sense…… ……further investigation is needed to define the best VTE prophylaxis…..” The International Myeloma Working Group PalumboA. et al., Leukemia 2008;22:414-423

12. Prevention of VTE in MM Which drug? efficacy safety ASA yes/? yes/? Warfarin Low fixed dose no yes Therapeutic dose yes no/? Low m.w.heparin yes yes

13. Prevention of VTE in MM patients receiving thalidomide or lenalidomide? When? Which Patient? At higher risk: Induction therapy High dose dexametasone, doxorubicine Multiagent chemotherapy + other risk factors: age, history of VTE, CVC, comorbidities, immobilization The International Myeloma Working Group Palumbo A. et al., Leukemia 2008;22:414-423