Irinotecan and Increased Triglyceride Level in Paraneoplastic Deep Venous Thrombosis (DVT): A Strange Link in An Old Problem

DVT is present in about 3–15% of cancer patients. Paraneoplastic thrombosis pathogenesis is multifactorial. Chemotherapy is frequently involved in DVT genesis as pro-inflammatory/pro-thrombotic factor. There are few data about incidence of DVT in patients treated with Irinotecan. Aim of our study is to define if thrombotic risk in patients treated with Irinotecan is increased and then which mechanism is probably involved. For this purpose we considered in our patients the complement fractions C3 and C4 and the immune circulating complex (ICC), because they activate macrophages and platelets and increase tissue factor level. Moreover we evaluated also total cholesterol and triglyceride level, cause linked with factor VII activation. We considered C3, C4, ICC, cholesterol and triglyceride level, dose density and chemotherapeutic agents used in 116 patients with solid neoplasms (62colon, 26lung, 18gastric,) and not receiving anticoagulant prophylaxis. Median age was 68.5 years (R 57–83). M/F ratio was 66/40. The threshold value of third quartile was chosen as risk cut-off (C3: 130mg/dl; C4: 32mg/dl; ICC: 2.9 mcg/ml; total cholesterol: 205mg/dl; triglycerides 120mg/dl). The statistical analysis was conducted with Yates corrected chi square test, Fisher’s exact test, Odds Ratio (OR), relative risk (RR). Twenty-four patients (20%) developed DVT. The patients treated with Irinotecan were 42. DVT occurred in 14 of these patients (32%) and in 10 of the 74 patients treated without Irinotecan (14%), with a Yates corrected chi square test of 4.6 (p=0.03), a Fisher’s exact test with p=0.03, an OR of 2.98 (95%CI 1.2–7.3) and a RR of 2.35 (95%CI 1.1– 4.8). C-Reactive Protein and Erythocyte Sedimentation Rate at Pearson’s test were not related with C3, C4, ICC, total cholesterol and triglyceride levels. All patients treated with Irinotecan had advanced stage colon cancer. High levels of triglycerides (>120mg/dl) were present in 17 out of 42 patients treated with Irinotecan (40%) and in 17 out of 74 patients treated without Irinotecan (23%) with a Yates corrected chi square test of 3.1 (p=0.07), a Fisher’s exact test with p=0.05, an OR of 2.2 (95%CI 1–5) and a RR of 1.7 (95%CI 1–3). Although most patients developing DVT have an advanced stage colon cancer and so receiving Irinotecan, the influence of chemotherapy in DVT pathogenesis in our study cannot be excluded. Probably Irinotecan could contribute to DVT increasing triglyceride levels that are linked with in vivo factor VII activation. This relief suggests also that risk factors, other than classical, should be considered in the thrombosis onset; then other drugs (i.e. hypolipemizing drugs) could be useful in paraneoplastic DVT prevention. Nevertheless these data should be confirmed in a larger cohort of patients.