Venous Thromboembolism in Lymphoma: How Effectively Are We Treating Patients?.

Introduction: Patients (pts) with solid tumors and venous thromboembolic episodes (VTE) have a high risk of complications (recurrent VTE/bleeding) during oral anticoagulant treatment. However, few data are available in pts with lymphoma. We conducted a retrospective study to determine the frequency of complications during oral anticoagulant treatment in lymphoma pts.

Methods: Charts of histologically proven non-Hodgkin’s (NHL) and Hodgkin lymphoma (HL) pts at our institution from January 1998 through April 2007 were retrospectively reviewed. After excluding pts with thrombocytosis, solid tumors, hypercoagulability or previous treatment with anticoagulants, pts with their first acute symptomatic VTE were identified (49 NHL, 8 HL). 31 were males and 26 females, with an age range of 40–89 years. The first symptomatic VTE was defined as lymphoma associated if the VTE occurred within 3 months before or after the biopsy diagnosis of the lymphoma but before chemotherapy. These VTE were confirmed by contrast venography or doppler ultrasound for venous thrombosis (neck and upper-lower extremities) and chest computed tomography, ventilation/perfusion scan, or pulmonary angiography for pulmonary embolism. Major bleeding was defined as bleeding that required transfusion, caused a drop of hemoglobin > 2 g/dL, or occurred in critical sites. Minor bleeding was defined as any overt bleeding that required stopping the anticoagulant treatment but not fulfilling the definition of major bleeding.

Results: All 57 pts were initially treated with high dose adjusted intravenous heparin or body weight adjusted low molecular weight heparin (LMWH). 46 pts were started on oral warfarin during the first 10 days of the initial treatment witch was continued for at least 3 months after discontinuing heparin. 11 pts received continuing LMWH and no warfarin. Recurrent VTE occurred in 14/46 pts on warfarin therapy. The international normalized ratio (INR) was within the therapeutic range (2.0–3.0) in 10/14 pts, and below the therapeutic INR (< 2.0) in 4/14 pts. Death was directly correlated to recurrent VTE (massive pulmonary embolism) in 2 pts in the warfarin treated group; a third death was caused by massive intracranial bleeding. Major bleeding was documented in 6/46 pts (4 pts had an INR within the therapeutic range, 2 had INR > 3), and minor bleeding in 9/46 pts. Recurrent VTE occurred in 1/11 pts treated with LMWH, major bleeding in 0/11 and minor bleeding in 3/11 pts with no deaths.

Conclusions: Previous studies showed an overall incidence of 27.1% recurrent thrombosis and 5.4% major bleeding in pts with malignancy treated with oral anticoagulant for VTE. Our study showed 30.4% recurrent thrombosis and 13% major bleeding in pts with lymphoma. Most bleeding and thrombotic complications occurred with an INR within the therapeutic range (65%). The percentage of serious complications was very high during the use of warfarin (43.5%), and the death rate 6.5%, compared to 9% and 0% during the use of LMWH. A high failure rate of oral anticoagulant treatment in pts with lymphoma suggests the need for alternative treatment. Since the number of pts in this retrospective study is small, a prospective randomized, controlled study comparing warfarin with LMWH is indicated.