Management of Venous Thromboembolism (VTE) in Thrombocytopenic Patients Undergoing Induction Chemotherapy for Acute Leukemia

Introduction: Management of VTE in patients with hematological malignancies is challenging as these patients often have thrombocytopenia and are at increased risk for bleeding. The International Society of Thrombosis and Hemostasis (ISTH) guidance statement recommends adjusting anticoagulation based on the severity and acuity of VTE and considering platelet transfusion support to maintain platelet counts above >50K/µL to facilitate full-dose anticoagulation (AC) in patients with acute VTE with high-risk features. For acute VTE with low-risk features, a dose-modified strategy such as half- or prophylactic-dose AC, depending on platelet count, is recommended. While the risk of AC with supportive platelet transfusions may be justified in patients with severe VTE, lower-dose AC without platelet transfusion support may be adequate for patients with non-severe VTE and may reduce the risk for development of platelet alloantibodies. To better understand practice patterns at our institution, we reviewed the management of VTE in patients with acute leukemia over an 8-year period.

Methods: We retrospectively reviewed all patients with acute leukemia who developed acute VTE during induction chemotherapy at Dartmouth-Hitchcock Medical Center for the 8-year period (2006-2013). Primary outcomes were 1) objectively confirmed, recurrent symptomatic VTE, and 2) clinically significant bleeding within 1 month after diagnosis of the index VTE. Secondary outcomes included IVC filter use and platelet alloantibody development within 3 months after diagnosis of VTE. We classified VTE events as acute or subacute/chronic and severe or non-severe. An acute event was defined as a new VTE diagnosed during the index hospitalization, while a subacute/chronic event was defined as a VTE that occurred prior to the index hospitalization for which the patient was being treated with AC during the hospitalization. A severe VTE was defined as a DVT involving femoral or more proximal vein segments, the SVC, cerebral veins or any PE. Non-severe events included UE DVT and distal DVT. We classified treatment at the time of diagnosis of VTE into one of the following categories: 1) full-dose AC with platelet transfusion to maintain platelet count >25-50K/µL, 2) half-dose AC with platelet transfusion to maintain platelet count >25-50K/µL, 3) prophylactic-dose AC without additional platelet transfusion beyond the standard of care, 4) no anticoagulation. We recorded the number of IVC filters inserted in each category. Descriptive statistics, including mean and standard deviation for continuous variables, and percentage and frequency for categorical variables, were calculated.

Results: 40 subjects met entry criteria (55% male) with median age of 57.5 years. The majority (88%) had acute myeloid leukemia. Acute VTE was identified in 80% and VTE was severe in 55%. The degree of thrombocytopenia at the time of VTE diagnosis was <10K/µL (2.5%), 10-25K/µL (25%), 25-50K/µL (40%), and >50K/µL (32.5%). Subjects were initially treated with full-dose AC (60%), half-dose AC (5%), prophylactic-dose AC (12%) or no AC (22.5%). An IVC filter was inserted in 10 subjects (25%), and five subjects (12%) developed platelet alloantibodies. Seventeen subjects (42%) experienced bleeding complications within the first month of VTE diagnosis, six of which (35%) were clinically significant. Half of these were on full-dose AC, and half underwent insertion of an IVC filter. Two subjects (5%) had VTE recurrence within 1 month, and in both cases, AC had been discontinued prior to the recurrence due to bleeding complications.

Conclusion: We found that management of VTE in patients with acute leukemia and thrombocytopenia varies and that the risk for bleeding complications was high irrespective of AC dose. We also uncovered the problem of VTE recurrence due to premature discontinuation of AC as a result of bleeding and observed a surprisingly high incidence of platelet alloimmunization. Dose-modified AC without platelet transfusion support may be an attractive alternative for treatment of VTE in this population, but further study is required to balance bleeding and thrombosis risk.