Post-surgery Use of Enoxaparin Lowered Blood Clot Risk

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by Patricia Inacio PhD |

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Treatment with the blood thinner enoxaparin within a few hours after curative pituitary surgery may help reduce the risk of blood clots forming in people with Cushing’s disease, a new study suggests.

The study “Venous thromboembolic (VTE) prophylaxis in Cushing disease patients undergoing transsphenoidal surgery” was published in the journal Interdisciplinary Neurosurgery: Advanced Techniques and Case Management.

Cushing’s syndrome results from elevated levels of the hormone cortisol, often due to a tumor in the pituitary or adrenal glands. When the source of the problem is the brain’s pituitary gland, the condition is known as Cushing’s disease.

People with Cushing’s have an increased risk for developing venous thromboembolism, or VTE, a condition that occurs when blood clots form in the deep veins of the legs, groin, or arms, and then travel and lodge in the lungs. This increased risk of VTE is linked to changes in blood-clotting processes, which can be prompted or further aggravated by surgery.

The gold standard treatment for Cushing’s disease is endoscopic transsphenoidal surgery (TSS) to remove the pituitary tumor. However, despite the known risk for blood clots forming in these patients, no consensus exists for the best time to introduce a preventive, or prophyatic, treatment for VTE following surgery, or for the most appropriate dose and duration of treatment.

In an effort to clarify this, a team led by researchers at the University of California Los Angeles conducted a retrospective analysis of Cushing’s disease patients who underwent endoscopic TSS at their institution from January 2010 to June 2020.

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Their final analysis included 64 patients (55 women and nine men, mean age of 38.8 years), all of whom received VTE prophylaxis at some point following surgery.

VTE prophylaxis was performed first using under-the skin (subcutaneous) injections of the natural anticoagulant heparin. In 2018, the protocol changed and heparin was replaced by subcutaneous injections of the anticoagulant enoxaparin, since it was associated with a lower risk of complications and potentially more effective.

Of the 64 patients, 44 (38 women and six men, mean age of 37.8 years) underwent treatment with heparin, consisting of 5,000 units twice daily starting the night after the surgery. The remaining 20 patients (17 women and three men, mean age of 40.8 years) received 40 mg of enoxaparin once daily, also starting the night after the surgery.

Both treatments were maintained until patients were discharged from the hospital. The average stay at the hospital in the heparin group was 3.41 days and in the enoxaparin group 3.45 days.

To reduce the risk of blood clot formation following surgery, all patients were advised to walk as soon as possible and to use compression sleeves on their legs.

Patients in the heparin group were followed for a mean of 49 months, and those in the enoxaparin for a mean of 11 months.

Only two (4.5%) patients — both in the heparin group — had a VTE episode. Yet, this was not considered statistically significant when compared with the incidence seen in enoxaparin group (0%). Both events were instances of pulmonary emboli (blood clots lodged in the lungs).

Within one month after surgery, the first patient developed tachycardia (rapid heartbeat) and was diagnosed with a blockage (embolus) in the lungs. The patient was treated with two anticoagulants, warfarin and enoxaparin.

The second patient developed pain in the right lower leg within five days after surgery. An ultrasound found a large blood clot in the leg and a CT angiography revealed the presence of blood clots in both lungs. (A CT angiography is an imaging test that uses X-rays and a dye to create detailed pictures of the heart and blood vessels.)

This patient received an heparin infusion, followed by enoxaparin injections for six months.

Neither patient had long-term complications as a result of the VTE. These complications were seen in a single patient of the enoxaparin group. The patient had a nosebleed (epistaxis) on the first day after surgery, which required a blood transfusion.

Overall, while Cushing’s disease patients undergoing TSS are at an increased risk of developing VTE, “pharmacologic prophylaxis while hospitalized may reduce the incidence of VTE in this population, and enoxaparin may be slightly more efficacious over subcutaneous heparin,” the researchers wrote.

“We recommend a protocol of enoxaparin, beginning the night of surgery and continuing throughout the hospital stay, lower extremity sequential compression devices during surgery, and encouragement of early ambulation [walking],” they wrote.

Investigators also noted that, “although it does not appear that VTE prophylaxis increases the rate of bleeding complications following TSS, patients should be advised about the potential for epistaxis and reassured that the risk is low.”