Enoxaparin Dose Reduction for Thrombocytopenia in Patients with Cancer: A Quality Assessment Study

Background: The development of chemotherapy-induced thrombocytopenia (CIT) in the setting of therapeutic anticoagulation for venous thromboembolic (VTE) disease is a common problem in cancer patients. The current approach to low molecular weight heparin (LMWH) dosing in the setting of CIT (Lee, AYY. J. Clin. Onc. 2009) is empirical and based on limited published experience. This approach was never validated prospectively. Since 2011, Memorial Sloan Kettering Cancer Center (MSKCC) implemented a similar guideline: administer full dose LMWH for a platelet count >50,000/mcL, half dose for a platelet count 25,000/mcL to 50,000/mcL and hold LMWH temporarily for a platelet count <25,000/mcL.

Materials and Methods: In a Quality Assessment project, we evaluated cancer patients at MSKCC who were on a therapeutic dose of enoxaparin for a VTE during the years 2011 through 2013, who experienced at least one period of thrombocytopenia (platelet count ≤50,000/mcL) for at least 7 days. We assessed for adherence to the LMWH dose modification guidelines reflected by dose reduction and/or temporary hold for existing or anticipated thrombocytopenia. In addition, major bleeding, clinically relevant non-major bleeding, recurrent VTE events, and death were recorded during the episodes of thrombocytopenia.

Results: We identified 101 patients with 144 episodes of thrombocytopenia, with an average duration of 21.3 days per episode. The LMWH dose was modified in 137 of the 144 episodes (95%), reflecting adherence to our institutional guidelines. The LMWH doses were reduced in 20 episodes, held in 90 episodes, and managed with combination of reduction/hold in 27 episodes. In general, the more severe thrombocytopenic episodes were managed with holding LMWH as opposed to dose reduction. The unweighted mean platelet count during episodes managed with holding LMWH was 27,000/mcL with a standard deviation (STD) of 16,000, while the mean platelet count during episodes of dose reduction was 36,000/mcL with a STD of 15,000.

There were no recurrent VTE events or major bleeding episodes when the LMWH was reduced or held. In our cohort, there was only one major bleeding episode, a trauma-associated retroperitoneal hemorrhage, which occurred on the third day of a thrombocytopenic episode, prior to enoxaparin dose modification. That patient's platelet count was 28,000/mcL at the time of the event. There were 14 clinically relevant non-major bleeding episodes, of which 7 cases consisted of ecchymosis, epistaxis or gingival bleeding. Lastly, 10 patients died during the episode of thrombocytopenia.

Discussion: This Quality Assessment project supports the safety and efficacy of our guidelines for therapeutic LMWH dose modification in the setting of CIT. In contrast to past case series, these patients were managed under direction of an institutional dosing guideline. We observed a 95% level of compliance with the guidelines. These data support the conclusion that the current LMWH dose reduction approach provides safety and efficacy, balancing the risks of recurrent thrombosis and bleeding during periods of CIT in cancer patients. It remains to be determined if a similar strategy would be appropriate for the new generation of oral anticoagulants.