Managing the competing risks of thrombosis, bleeding, and anticoagulation in patients with malignancy

Abstract

The association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patients with hematologic malignancies and those treated with intensive myelosuppressive chemotherapy regimens. Despite the advancements in cancer-directed therapy made over the past 15 years, numerous large studies have confirmed that bleeding and VTE recurrence rates remain high in cancer patients. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult, because management of cancer-associated thrombosis requires anticoagulation despite known increased risks for bleeding. In the context of challenging illustrative cases, this review will describe management approaches to clinical scenarios in which data are sparse: cancer patients with recurrent VTE despite anticoagulation and cancer patients with a new VTE in the setting of severe thrombocytopenia.

Figure 1.

Summary of evidence and guidelines for treatment of acute VTE in the thrombocytopenic cancer patient. Recommendations for each anticoagulant and platelet thresholds are based on published consensus guidelines or major published trials and studies. For patients that cannot be transfused, timing of onset and severity of VTE must be considered. ^aHigh risk for thrombus propagation is defined as acute proximal or recurrent thrombosis. ^bDabigatran is not displayed as an option because of the lack of data, studies, or discussion in guideline statements. ^cThe ISTH and NCCN guidelines recommend holding anticoagulation at platelet counts of <25 000/µL, whereas the ASCO guidelines use a threshold of 20 000/µL. ^dLow-dose LMWH is generally defined as prophylactic dosing (eg, 30-40 mg enoxaparin daily or 5000 U dalteparin daily), and intermediate-dose LMWH is variably defined as enoxaparin 0.5 mg/kg twice daily or 1 mg/kg once daily (Table 2). ^eDefined in this study as rivaroxaban 10 mg twice daily during the first 3 weeks of treatment or 10 mg once daily after the first 3 weeks of treatment. Plt, platelet count.