Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study

Abstract

Venous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multi-center, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count < 100,000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at six hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%), 33 (27%) with modified-dose anticoagulation, while 13 (11%) received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33, 94%) and an acute DVT (28 of 33, 85%). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% CI, 4.9-20.8%) and 6.6% (95% CI, 2.4-15.7%) in those who received modified-dose anticoagulation (Fine-Gray HR 2.18, 95% CI 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11%) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop DVT in the setting of thrombocytopenia.

Platelet transfusion and anticoagulation in hematological cancer‐associated thrombosis and thrombocytopenia: The CAVEaT multicenter prospective cohort

“…Our data confirm the high rates of bleeding in patients with thrombosis and thrombocytopenia with clinically relevant bleeding in 29% of patients and major bleeding in 8% by 90 days, demonstrating a similar pattern to the VENUS cohort of patients with acute thrombosis, any malignancy, and platelets <100 × 10 9 /L in which there was bleeding in 24% and major bleeding in 9% by 60 days 3 …”

“…This variability in practice reflects a limited evidence base, with guideline recommendations based on consensus. A recently published prospective cohort from the Venous thromboEmbolism Network U.S. (VENUS) describing management and outcomes of 121 patients with any malignancy, thrombosis within 7 days, and platelet count <100 × 10 9 /L has described marked variation in practice and frequent changes in the anticoagulation strategy for individual patients over time, reporting high rates of bleeding (24% by 60 days), and a rate of VTE recurrence of 5.6% by 60 days 3 . A systematic review examined the important question of whether it is preferable in the presence of severe thrombocytopenia to use platelet transfusion to support full dose anticoagulation, or to reduce or withhold anticoagulation: 4 the authors identified only two relevant retrospective observational studies including a total of 121 patients with cancer‐associated thrombosis and thrombocytopenia.…”

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

“… 5 In a prospective non-randomised study of patients with VTE and thrombocytopenia (platelets <100 × 10 9 per L, n=121), the 60-day incidence of major bleeding was 12·8% (95% CI 4·9–20·8) with full-dose anticoagulation, and 6·6% (95% CI 2·4–14·7) with a lower dose anticoagulation (HR 2·18, 95% CI 1·21–3·93). 82 The incidence of recurrent VTE was 5·6% (95% CI 0·2–11%) with full-dose anticoagulation and 0% with modified-dose anticoagulation. 82 One retrospective study of 15 337 patients with cancer reported that patients with severe thrombocytopenia (platelets <50 × 10 9 per L, n=166) compared with patients who had a normal platelet count had a similar risk for major bleeding at 10 days (OR 0·84, 95% CI 0·20–3·49) and 30 days (0·90, 0·32–2·49), regardless of the LMWH dose used.…”

“… 82 The incidence of recurrent VTE was 5·6% (95% CI 0·2–11%) with full-dose anticoagulation and 0% with modified-dose anticoagulation. 82 One retrospective study of 15 337 patients with cancer reported that patients with severe thrombocytopenia (platelets <50 × 10 9 per L, n=166) compared with patients who had a normal platelet count had a similar risk for major bleeding at 10 days (OR 0·84, 95% CI 0·20–3·49) and 30 days (0·90, 0·32–2·49), regardless of the LMWH dose used. 83 …”

Challenging issues in the management of cancer-associated venous thromboembolism

“…There is a lack of data on the use of DOACs in patients with cancer-associated VTE and thrombocytopenia because major pivotal trials of DOACs on cancer-associated VTE did not include patients with platelet counts <50,000–100,000/mL at baseline [ 11 , 30 - 32 ]. In a recent small multicenter prospective study evaluating the risk of hemorrhage and recurrent VTE in patients with cancer-associated VTE and concurrent thrombocytopenia (platelet counts <100,000/mL) [ 33 ], modified dose anticoagulation, including 2.5 mg apixaban twice daily and 10 mg rivaroxaban daily, has shown to be a safe alternative approach. Thus, DOACs are urgently needed to be investigated in patients with cancer with VTE in the setting of thrombocytopenia.…”