Bleeding Risk in Thrombocytopenic Cancer Patients with Venous Thromboembolism (VTE) Receiving Anticoagulation

Cancer-associated thromboses are commonly treated with anticoagulants, which sometimes cause bleeding. Cancer patients receiving chemotherapy develop thrombocytopenia and these patients are at an increased risk of bleeding. Because of concerns about bleeding risk when one combines anticoagulation and thrombocytopenia, the National Comprehensive Cancer Network considers a platelet count of less than 50,000/cmm as a contraindication to anticoagulation and the American Society of Clinical Oncology recommends anticoagulation in thrombocytopenic cancer patients with caution. This retrospective chart review aims to evaluate bleeding risks associated with anticoagulation in cancer patients with platelet counts of less than 50,000/cmm.

From Jaunary 2008 to January 2011 chart reviews were made of 2,711 patients (18 years or older) with ICD9 diagnoses emcompassing venous thromboembolism and thrombocytopenia. The following cases were excluded from the study, (1) no anticoagulation, (2) platelet count above 50,000/cmm, (3) tumor thrombus, (4) asynchronous thrombosis and thrombocytopenia, (5) therapeutic embolization, (6) history of thrombotic events, (7) history of thrombocytopenia. The primary end point was bleeding and the secondary end point was recurrent thrombosis.

53 patients were identified; male: female = 1.2 : 1.0, median age 58 (range 19 – 84), hematologic malignancies (including myelodysplasia): solid tumors = 1.8 : 1.0, median stage of cancer = 4.0, median baseline RIETE bleeding risk score = 2.5 (range 1.0 – 5.0), median platelet count at the start of anticoagulation = 33,000/cmm (range 18,000 – 49,000/cmm), median duration of anticoagulation = 83 days (range 4 – 740 days), DVT only = 35 cases, PE only = 13 cases, DVT + PE = 5 cases, unilateral DVT: bilateral DVT = 7 : 1, upper extremity DVT: lower extremity DVT = 1.3 : 1.0. 44 patients were treated with low molecular weight heparin (LMWH), 5 patients were treated with fondaparinux and 4 patients were treated with unfractionated heparin (UFH). 23 patients received anticoagulation for less than 3 months, including 11 patients who received it for < 14 days. 15 patients had ≥ 25% dose reductions of anticoagulants. Overall, 5/53 patients (9.4%) suffered bleeding while receiving anticoagulation. Using the WHO bleeding scale, there was 1 grade 5 bleeding event (cerebral hemorrhage in a patient with AML being treated with UFH infusion for cavernous sinus thrombosis); 1 grade 4 bleeding event (tracheostomy hemorrhage in a patient receiving therapeutic dose fondaparinux) and 3 grade 2 bleeding events (1 epistaxis while on therapeutic enoxaparin 1mg/kg/12 hours, 1 case of oozing from bone marrow biopsy site while on dalteparin 200 IU/kg/day and 1 episode of hematuria while on reduced dose enoxaparin 1mg/kg/day). Overall, there was a 1 recurrent thrombotic episode (1.8%), which occurred in a patient receiving dalteparin 100 IU/kg/day.

We conclude that anticoagulation during periods of thrombocytopenia < 50,000/cmm is feasible and may be safe. Major bleeding risk (WHO grades 3, 4 and 5) was 2/53 (3.8%). This is comparable to the 6% major bleeding rate observed with 6 months of standard LMWH anticoagulation in cancer patients with platelet counts above 75,000/cmm, as reported in the CLOT trial (N Engl J Med 2003;349:146–53). Recurrence risk is 1/53 (1.8%). This is less than the 9% six month recurrence rate observed in those treated with LMWH in the CLOT trial. Our data also suggest that the impact of anticoagulation dose-reduction appears to be minor. Validation of our conclusions will require prospective studies, which also would provide a thrust towards optimizing the therapeutic index of anticoagulation therapy in thrombocytopenic cancer patients suffering from VTE.

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