Impact of thrombocytopenia on clinical outcomes in patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT Study

Abstract Background The ONCO DVT study revealed the potential benefit of prolonged anticoagulation therapy for cancer patients with isolated distal deep vein thrombosis (DVT) in terms of thrombotic events without an increased risk of major bleeding. However, it has been still uncertain whether these results are applicable to patients with thrombocytopenia, who could be at a high risk of bleeding. Purpose The purpose of this study is to evaluate the impact of thrombocytopenia on clinical outcomes, including thrombotic and bleeding events, in cancer patients with isolated distal DVT who received prolonged anticoagulation therapy. Methods The ONCO DVT study was a randomized clinical trial which randomly assigned cancer patients with isolated distal DVT to receive either 12-month or 3-month edoxaban treatment in a 1-to-1 ratio and evaluated clinical outcomes at 12 months. In this pre-specified subgroup analysis of the ONCO DVT study, 601 patients were stratified into the thrombocytopenia (N=31) and no thrombocytopenia (N=570) subgroups. Thrombocytopenia was defined as platelet count 100,000/µl. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months. Results The median baseline platelet count at diagnosis was 236,000/µl (interquartile range, 180,000 to 298,000/µl). There was no significant difference in baseline characteristics including age, sex, body weight, or dosing of edoxaban between the 2 subgroups, whereas patients in the thrombocytopenia subgroup were more likely to be treated with chemotherapy (87% vs 45%, P 0.001), and more frequently had a history of major bleeding (13% vs 3.3%, P =0.03) and anemia (94% vs 65%, P 0.001). Patient characteristics were well balanced between the 12-month and 3-month edoxaban groups in both subgroups. In the thrombocytopenia subgroup, the primary endpoint did not occur in the 12-month group, and occurred in 1 of 19 (5.3%) patients in the 3-month group, whereas in the no thrombocytopenia subgroup, the primary endpoint occurred in 3 of 284 (1.1%) patients in the 12-month group, and in 21 of 286 (7.3%) patients in the 3-month group (OR 0.14; 95% CI 0.04–0.47) (P interaction =0.68). In the thrombocytopenia subgroup, the major secondary endpoint occurred in 5 of 12 (41.7%) patients in the 12-month group, and did not occur in the 3-month group, whereas in the no-thrombocytopenia subgroup, the major secondary endpoint occurred in 23 of 284 (8.1%) patients in the 12-month group, and in 22 of 286 (7.7%) patients in the 3-month group (OR 1.05; 95% CI 0.58–1.88) (P interaction =0.002) (Figure). Conclusions In patients with cancer-associated isolated distal DVT and thrombocytopenia, there was a potential increased risk of major bleeding with prolonged anticoagulation therapy, which suggested some concerns on the risk-benefit balance of prolonged anticoagulation therapy for these patients.