1616P - Low Molecular Weight Heparin (LMWH) Resistance in Cancer Patients

Abstract

ABSTRACT Introduction Cancer patients have an increased risk of developing venous thrombo-embolism (VTE). Treatment of VTE involves the administration of heparin, low molecular weight heparin (LMWH) or coumarin derivatives. Heparin resistance is a situation in which the administration of heparin does not result in an increase of the activated partial thromboplastin time (APTT) and blood anticoagulation. While heparin resistance is a known entity, LMWH resistance is not well documented, and anti factor Xa activity is not tested routinely in cancer patients treated with LMWH. Here, we report the pharmacokinetics of LMWH in cancer patients suffering from VTE and receiving treatment with enoxaparin at standard doses of 1 mg/kg twice daily. Patients/methods Patients suffering from malignancy and VTE, and treated with the LMWH, enoxaparin at standard dose of 1mg/kg q12 hr were enrolled. Ambulatory patients were admitted to the oncology day care unit for 8 hours in order to facilitate repeated blood testing. Blood samples were obtained before the injection of LMWH and 1, 2, 3, 4, 6 and 8 hours after LMWH subcutaneous administration, and tested for anti Xa activity as a surrogate marker of bioavailable LMWH levels. The trial was approved by the ethics committee of Shaare Zedek Medical Center. ClinicalTrials.gov Identifier: NCT00716898. Study funding: Israel Cancer Association. Results Eleven patients were enrolled; one was excluded from analysis due to complete remission at time of VTE diagnosis. Peak anti Xa activity was achieved after 2, 3, 4, 6, and 8 hours in 2, 3, 2, 2, and 1 patient respectively. 60% of the patients (n = 6) did not reach the therapeutic anti Xa activity target (0.6 -1.0 IU/ml) at 4 hours after subcutaneous administration of LMWH. Average anti Xa activity at 4 hours was 0.62 ± 0.29 IU/ml as opposed to 1.1 IU/ml in historical controls of non-oncology patients. Conclusions Our results show that a substantial number of cancer patients suffering from VTE and treated with standard dose enoxoparin do not reach therapeutic target anti Xa activity. If confirmed in a larger study, our results suggests that cancer patients suffering from VTE should be tested for anti Xa activity and LMWH dose should be titrated accordingly in order to achieve effective anticoagulation. Disclosure All authors have declared no conflicts of interest.