Tailored Doses of Enoxaparin Better Prevent VTE After Cancer Surgery

By Will Boggs MD

January 17, 2020

NEW YORK (Reuters Health) - Adjusting the doses of enoxaparin based on anti-Xa levels, instead of using standard doses, may better prevent venous thromboembolism (VTE) without worsening bleeding rates in patients undergoing abdominal cancer surgery, according to a new study.

"What we found most surprising is that majority of patients who underwent cancer surgery were found to have inadequate doses of deep-vein thrombosis (DVT) prophylaxis (enoxaparin) based on current recommended guidelines," said Dr. Gitonga Munene of Western Michigan University Homer Stryker MD school of medicine, in Kalamazoo, Michigan.

"This indicates that we may not be reducing the risk of DVT and pulmonary embolism (PE) in the majority of cancer-surgery patients if we continue using the current recommended doses," he told Reuters Health by email.

Patients with cancer already have an increased risk of VTE, and cancer surgery further elevates that risk. The presence of VTE after major cancer surgery has been associated with a five-fold increase in the risk of mortality. Enoxaparin, a low-molecular-weight heparin, is widely used to prevent VTE after cancer surgery.

Dr. Munene's team examined the efficacy and safety of dose-adjusted enoxaparin guided by anti-Xa levels in 64 prospectively enrolled patients undergoing abdominal cancer surgery versus recommended thromboprophylaxis doses (unfractionated heparin 5000 U three times daily or enoxaparin 40 mg once daily) in a historical control group of 133 similar patients.

Patients in the intervention group had initial enoxaparin doses of 40 mg once daily. If their initial anti-Xa level was below 0.2 IU/mL, the dose was increased to 30 mg twice daily, and subsequent doses were increased by 10 mg per dose until serum anti-Xa levels were between 0.2 and 0.4 IU/mL, the maximum dose of enoxaparin 60 mg twice daily was reached, or the patient was discharged from the hospital.

None of the patients in the intervention group developed VTE, whereas 11 patients (8%, P=0.018) in the control group developed VTE, including six patients (11%) receiving enoxaparin and five (7%) receiving heparin.

The groups did not differ significantly in major bleeding events, postoperative transfusion requirements, or mean discharge hemoglobin levels, the researchers report in the Journal of the American College of Surgeons.

In the intervention arm, only 14 of 64 patients (22%) achieved an initial prophylactic anti-Xa level of at least 0.2 IU/mL. Overall, 23 patients required one adjustment in enoxaparin dosing, and 12 patients required two adjustments in enoxaparin dosing.

Seven patients remained subprophylactic after two adjustments but did not remain hospitalized long enough to have a fourth anti-Xa level drawn.

Patients with doses that were initially subprophylactic were significantly younger, had a higher BMI and a longer operative time than did patients with initially prophylactic doses of enoxaparin.

"Current guidelines for DVT thromboprophylaxis in cancer surgery and trauma surgery (published data by another group) and other high-risk surgeries may need to be revised to reflect the use of anti-Xa levels in determining correct dosage of enoxaparin," Dr. Munene said. "Additional randomized trials would need to be conducted to document and confirm the efficacy and safety of this approach in cancer patients and other surgery patients."

Dr. Taishi Hata from Kansai Rosai Hospital, in Amagasaki, Japan, and colleagues recently reported that anticoagulant prophylaxis with enoxaparin or fondaparinux did not significantly reduce the incidence of VTE following laparoscopic colorectal cancer surgery. He told Reuters Health by email, "Cancer patients are VTE high risk, and they may need more doses of enoxaparin than non-cancer patients."

"The recommended dose of enoxaparin by guideline may be too low for cancer patients," said Dr. Hata, who was not involved in the new work.

SOURCE: https://bit.ly/37PJJoI Journal of the American College of Surgeons, online December 13, 2019.