Prophylaxis of Thromboembolism with Low-Molecular-Weight Heparins in Oncology Patients: Efficacy and Safety of Doses Adjusted According to Anti-Xa Activity

Introduction

Studies in populations at high risk of thromboembolic disease have shown that the recommended doses of enoxaparin for the prophylaxis of thromboembolic complications are associated with a higher incidence of subprophylactic values of measured anti-Xa activity. Determining anti-Xa activity is among the important parameters for monitoring the efficacy and safety of therapy. Prophylactic anti-Xa activity measured 3–4 hours after LMWH application typically ranges between 0.2–0.4 IU/ml, while therapeutic activity ranges between 0.5–1.0 IU/ml. A recently published study evaluated the efficacy and safety of adjusting the dose of enoxaparin based on the established anti-Xa activity in oncological patients undergoing surgical procedures.

Methods and Study Aims

The study prospectively included patients undergoing surgical procedures for abdominal malignancy, where the dose of enoxaparin was adjusted to achieve a peak anti-Xa activity of > 0.2 IU/ml. Participants were compared with a historical cohort where prophylaxis was based on empirically recommended dosing of enoxaparin. The study aimed to monitor the incidence of thromboembolic disease and major bleeding during hospitalization following the dose adjustment of enoxaparin.

Study Population

A total of 197 patients participated in the study, with 64 in the prospective intervention group and 133 forming the control group. The baseline characteristics of both groups were similar, differing only in the Caprini risk score for thromboembolic complications (8.09 vs. 7.26; p = 0.013). A subprophylactic dose of enoxaparin was initially observed in 50 out of 64 patients (78.1%) in the intervention group.

Results

The intervention group showed a lower incidence of thromboembolic disease compared to the control group (0 vs. 8.27 %; p = 0.018). There was no significant difference in the incidence of major bleeding (3.12 vs. 1.50 %; p = 0.597), the number of red blood cell transfusions after surgery (17.2 vs. 23.3 %; p = 0.426), or the average hemoglobin value at the end of hospitalization (95.8 vs. 93.7 g/l; p = 0.414).

Conclusion

Prophylaxis with enoxaparin at a dose of 40 mg/day is often associated with subprophylactic anti-Xa activity. Adjusting the dose according to measured anti-Xa activity reduces the incidence of thromboembolic disease without increasing the risk of major bleeding events compared to conventional dosing.

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Source: Kramme K., Sarraf P., Munene G. Prophylactic enoxaparin adjusted by anti-factor Xa peak levels compared with recommended thromboprophylaxis and rates of clinically evident venous thromboembolism in surgical oncology patients. J Am Coll Surg 2019 Dec 13, pii: S1072-7515(19)32232-X, doi: 10.1016/j.jamcollsurg.2019.11.012 [Epub ahead of print].