Blood clots with no symptoms found after Cushing’s disease surgery
Small study found asymptomatic clots in legs in nearly 7% of patients
In people with Cushing’s disease, it is relatively common for blood clots that cause no symptoms — called asymptomatic blood clots — to appear in the legs after surgery, a new study reported.
Indeed, in a case series of 30 Cushing’s patients who underwent surgery and screening with compression ultrasound, two — nearly 7% — were found to have asymptomatic blood clots, called venous thrombotic events, in the legs (VTE-L). These clots occurred despite all patients receiving preventive treatment with heparin, an anticoagulant, commonly called a blood thinner which is used to stop blood from clotting too easily.
However, the small size of the study means that conclusive evidence is still needed to determine the merits of screening patients using this technique.
“Further large-scale compression ultrasound screening studies are needed to determine the risk of progression to symptomatic venous thromboembolic events in these patients,” the researchers wrote.
The study, “Prevalence of perioperative asymptomatic venous thromboses of the lower extremity in 30 consecutive patients undergoing transsphenoidal surgery for Cushing’s disease,” was published in the journal Scientific Reports.
Screening for blood clots in Cushing’s disease patients post surgery
Cushing’s disease is caused by benign tumors in the brain’s pituitary gland. These tumors ultimately lead to elevated levels of the hormone cortisol, which causes a wide variety of symptoms, such as weight gain, skin problems, and fat accumulation in specific parts of the body.
In most cases, surgery to remove the tumors is the recommended treatment for Cushing’s disease. Studies have shown that people with Cushing’s disease have a higher risk of developing blood clots than the general population, and that this risk increases substantially after surgery.
However, little is known about the prevalence of asymptomatic VTE-L in these patients after surgery. These types of blood clots are easily missed due to the lack of overt symptoms, but they can progress and move, becoming symptomatic, or lodge in the lungs and become life-threatening.
To learn more, a research team in Germany designed a case series to evaluate Cushing’s patients who underwent surgery at a pituitary referral center. Each patient was offered screening with compression ultrasound, a noninvasive technique that is commonly used to detect blood clots.
The goal of the study was to determine the prevalence of asymptomatic VTE-L in people with Cushing’s disease who underwent tumor removal surgery and to assess possible clinical or demographic factors linked to the occurrence of VTE-L.
Of the 36 patients who underwent surgery at the center between October 2018 and September 2019, 30 had confirmed Cushing’s disease and agreed to be screened for VTE-L with compression ultrasound.
The participants had a median age of 46, and nine were men. All of them received heparin as a preventive anticoagulation treatment, administered once daily via an under-the-skin (subcutaneous) injection for at least two weeks after surgery. Compression ultrasound was done in the first week after surgery, at a median of two days after the procedure.
Two (6.7%) of the 30 participants were found to have an asymptomatic VTE-L — one in a deep leg vein, called posterior tibial vein, and the other in muscle veins of the calf.
No significant differences were found between the two patients with a VTE-L and the rest of the group in terms of demographic and physical aspects, the presence of other diseases or conditions, cardiovascular risk factors, and use of anticoagulant medications.
Both patients with clots were men despite a smaller number in study
Interestingly, both individuals with a VTE-L were men whereas the proportion of male patients in the non-VTE-L group was only 25%. However, this difference was not statistically significant.
In laboratory tests done before surgery, patients with a VTE-L had significantly higher levels of morning cortisol in the blood than those in the non-VTE group (mean of 421.0 vs. 188.1 micrograms per liter).
Patients with a VTE-L also had significant differences in blood clotting parameters compared with the non-VTE-L group, including higher von Willebrand factor activity, lower levels of fibrinogen, and a longer time needed to form blood clots.
The two patients with a VTE-L were treated with the anticoagulant enoxaparin, given subcutaneously twice per day for three months after the VTE-L was found.
Over the course of follow-up, which lasted a mean of 7.4 months after surgery, none of the 30 patients in the study had a symptomatic blood clotting event, in the legs or otherwise.
In a larger [Cushing’s disease] patient population, which is difficult to reach because of the rarity of this condition, it may be possible to identify demographic and clinical risk factors in the future.
“Early postoperative ultrasound screening may have detected asymptomatic distal VTE-L in [Cushing’s disease] patients at an early stage, which, if left untreated, might have later developed into symptomatic proximal VTE-L,” the researchers wrote.
This study showed that post-surgery screening of patients with compression ultrasound to detect asymptomatic VTE-Ls might have merit. However, the small size of the study, with only two patients having a VTE-L, compromises any definite conclusions. Until larger and prospective studies can be done to confirm the benefits of this type of screening, the research team noted that no recommendations for clinical practice can be made.
Studies with more patients from different centers also are crucial to assess any clinical or demographic differences that might distinguish those at risk of a VTE-L from others less susceptible.
“In a larger [Cushing’s disease] patient population, which is difficult to reach because of the rarity of this condition, it may be possible to identify demographic and clinical risk factors in the future,” the team wrote.
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