Hypercoagulability in Cushing’s syndrome: incidence, pathogenesis and need for thromboprophylaxis protocols

Abstract

Cushing's syndrome (CS) is associated with a hypercoagulable state resulting in an increased risk on venous thromboembolism (VTE). In patients with untreated active CS VTE incidence is up to 18-fold higher compared to the general population, whereas after pituitary and adrenal surgery a postoperative VTE risk between 2.6 and 5.6% has been reported. Interestingly, after surgery the VTE risk is not only increased in the first week but also during several months postoperatively. The hypercoagulable state in CS is thought to be caused, at least in part, by an imbalance between activity of pro- and anticoagulant pathways. However, changes in activated partial thromboplastin time and plasma concentrations of pro-and anticoagulant factors are not observed in every CS patient. Only retrospective studies have shown that thromboprophylaxis lowers VTE risk in CS. Future prospective studies should asses the optimal timing, duration and type of thromboprophylaxis in CS to improve VTE-related morbidity and mortality.

Pregnancy complicated with adrenal adenoma causing ACTH-independent Cushing’s syndrome, accompanied by obstetric antiphospholipid syndrome and severe pre-eclampsia: case report and literature review

“…Cushing's syndrome is associated with hypercoagulable state, leading to an increased risk of venous thromboembolism (VTE) (62). Among untreated CS patients, the incidence of VTE was 18 times higher than that of the general population, and the risk of VTE decreased significantly after surgical resection of adrenal tumors (63). The hypercoagulable state of CS is not fully understood, and some studies suggest that it is caused by the imbalance between activity of procoagulant and anticoagulant pathways (62).…”

“…The hypercoagulable state of CS is not fully understood, and some studies suggest that it is caused by the imbalance between activity of procoagulant and anticoagulant pathways (62). Functional analysis showed that the partially activated thromboplastin time was shortened and the thrombolysis time was increased in patients with CS (63,64). This may aggravate the coagulation dysfunction in patients with OAPS, affect uterine and placental circulation, and lead to a series of adverse pregnancy outcomes (11,16,63,64).…”

“…Functional analysis showed that the partially activated thromboplastin time was shortened and the thrombolysis time was increased in patients with CS (63,64). This may aggravate the coagulation dysfunction in patients with OAPS, affect uterine and placental circulation, and lead to a series of adverse pregnancy outcomes (11,16,63,64). There is no standard scheme for preoperative or postoperative thrombus prevention in patients with CS complicated with OAPS.…”

Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey

“…It is well-known that endogenous hypercortisolism is associated with increased morbidity and mortality ( 4 , 5 , 6 ). This increased risk is mainly driven by cardiovascular events, including venous thromboembolic events (VTEs) such as pulmonary embolism (PE) and deep vein thrombosis (DVT).…”

Special issue: Cushing's disease update

“…Several complications of CS have recently been more readily recognized, requiring new personalized treatment and prohylaxis protocols. These include hypercoagulability [15] and increased risk of venous thromboembolism (up to 18 times higher than normal population), cardiovascular disease [16] as the main cause of mortality and associated multifactorial bone disease [17]. In some patients, although growth hormone deficiency [18] may improve after surgical resection, low IGF-1 has been linked to persistent myopathy.…”