Cancer and Thrombosis Friday September 30, 2011 Kelly Cheung, BSc, BSP Learning Objectives 1. Recognize the association and risk factors between cancer and venous thromboembolism 2. Identify anti-cancer therapies that are associated with an increased risk of thrombosis 3. Review guidelines/recommendations for the use of VTE prophylaxis in cancer patients Risk Factors for VTE in Cancer Patient factors – Age – Race – Elevated biomarkers – Performance status – Comorbidities: heart failure, respiratory failure, obesity, diabetes, previous VTE, infection, familial and/or acquired hypercoagulability J Clin Oncol 25:5490-5505, Hematology 2010:144-149 Risk Factors for VTE in Cancer (cont’d) Cancer-related factors – Primary site of cancer – GI, brain, lung, gynecologic, renal, hematologic – First 3-6 months after diagnosis – Metastatic and/or bulky disease J Clin Oncol 25:5490-5505 Risk Factors for VTE in Cancer (cont’d) Treatment-related factors – Surgery – Hospitalization – Chemotherapy – Hormonal therapy – Antiangiogenic therapy – Erythropoesis-stimulating agents – Central venous catheters J Clin Oncol 25:5490-5505 Virchow’s Triad in Cancer Venous stasis – Prolonged bed rest/immobility – Compression of blood vessels by tumour Vascular damage – Direct invasion by tumour – Central Venous Catheters – Chemotherapy drugs – Tumour cytokines J Clin Oncol 25:5490-5505 Virchow’s Triad in Cancer (cont’d) Hypercoagulability – Procoagulant effects – Fibrinolytic activity – Tumour cytokines – Impaired endothelial cell defense mechanisms – Tumour cell/host cell interactions – Prothrombotic effects of cancer therapy and supportive therapy Winter et al. Hematological Oncology 2006;24:126-133 Anti-cancer therapies associated with increased risk of thrombosis Antiangiogenic agents (thalidomide and lenalidomide) and their combinations VEGF inhibitors (bevacizumab) SERMs (tamoxifen, raloxifene) Supportive Therapies: erythropoietin, growth factors and hormones Guidelines for VTE Prophylaxis - IMIDs Risk Group High Clinical Factors ♦ IMID and previous personal history of VTE ♦ IMIDs plus other therapy (high dose dexamethasone, doxorubicin or multiagent chemotherapy) Intermediate • ♦ IMID and any 2 VTE risk factors such as: o Strong family history of VTE or known thrombophilia o Obesity o Prolonged immobilization o Indwelling catheters o Additional medication with VTE risk (estrogens, EPO) o Additional comorbidities that can additionally increase the risk (nephrotic syndrome, aggressive disease) Recommendation ♦ Prophylactic dose of LWMH ♦ Warfarin adjusted for INR 2-3 • Prophylactic dose of LMWH or adjusted warfarin for INR 2-3 if bleeding risk is low • If risk of bleeding is high (prior uncontrolled bleed, platelet count <80x10 9/L or difficult to control warfarin) then reasonable to offer ECASA 81mg OD IMID therapy is the only VTE risk ♦ factor IMID = immunomodulatory drug (thalidomide or lenalidomide) Low ECASA 81mg OD Taken from CCMB Evidence-Based Recommendations for the Management of Multiple Myeloma, July 2011 update. Table prepared by Dr. Vi Dao Guidelines for VTE Prophylaxis IMIDs High risk patients: warfarin (target INR 23) or prophylactic LMWH for at least 4-6 months. May continue for the entire duration of treatment or can consider switching to ASA Low risk patients: ECASA 81mg OD is favoured Intermediate risk: prophylactic LMWH or warfarin (target INR 2-3) is preferred unless high bleeding risk CCMB Evidence-Based Recommendations for the Management of Multiple Myeloma, July 2011 update. Section prepared by Dr. Vi Dao. Guidelines for VTE Prophylaxis – Other Therapies Bevacizumab is associated with increased risk of VTE; however, also associated with increased risk of bleeding – No routine VTE prophylaxis recommended Routine prophylaxis not recommended for patients with CVC Current guidelines do not recommend routine VTE prophylaxis in ambulatory patients with cancer Conclusions The potential causes of VTE in cancer are multifactorial In the ambulatory setting, only patients receiving thalidomide/lenalidomide treatment require VTE prophylaxis – Choice of prophylactic agent depends on patient factors Further studies are required to determine if routine prophylaxis would be of benefit and for which patient subgroups