Perioperative thromboprophylaxis in Cushing’s disease: What we did and what we are doing?

Barbot, Mattia; Daidone, Viviana; Zilio, Marialuisa; Albiger, Nora; Mazzai, Linda; Sartori, Maria Teresa; Frigo, Anna Chiara; Scanarini, M.; Denaro, Luca; Boscaro, Marco; Casonato, Sandra; Ceccato, Filippo; Scaroni, Carla

doi:10.1007/s11102-014-0600-y

Cited by 49 publications

(60 citation statements)

References 31 publications

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“…the thromboembolic events were related to surgery, whereas VTE unrelated to surgery was reported in 44% of the patients with CS (9,14,15,32,36,38,39,40,47,48,49,50,51). VTE was reported as the cause of death in 11% (13/121) of the patients with CS.…”

Section: :4 M16mentioning

confidence: 98%

“…This elevation in endogenous anticoagulants is probably secondary to the high levels of procoagulant factors, which represent a protective mechanism against hypercoagulability in these patients. However, an increase in factors that inhibit fibrinolysis, such as PAI1 (6,14,32,34,35,36,38), TAFI (36) and a2-antiplasmin (36, 43), was also reported, which demonstrates that the fibrinolytic pathway is also impaired in hypercortisolism.…”

Section: Figurementioning

confidence: 99%

“…Most of the studies that have evaluated the procoagulant factors in patients with hypercortisolism have found a decrease in PTT values (5,6,7,14,32,33,34,35,36,37,38) and an increase in the plasma levels of The factor Xa converts prothrombin (factor II) into thrombin (factor IIa) in the presence of ionized calcium and factor Va.…”

Section: Hypercoagulabilitymentioning

confidence: 99%

“…In one systematic review, the authors observed that even after remission of hypercortisolism, vWF, VIII, and IX factors remained high (42). With respect to endogenous anticoagulants, two studies found an increase in PS, PC, and AT plasma levels (14,38). Moreover, an increase in the elements involved in the fibrinolytic pathway, such as plasminogen and tPA, was described (6,7).…”

Section: Figurementioning

confidence: 99%

“…It is recognized that the use of preoperative cortisol-lowering medications might prevent the occurrence of postoperative VTE by reducing the cortisol withdrawal syndrome that can trigger an inflammatory state, which results in an increase in acute-phase proteins like FVIII and fibrinogen (38). Of the 13 studies included, only four evaluated the use of ketoconazole before surgery (32,36,38,51). Furthermore, as stated earlier in the present review, hypercoagulability in CS may be related to arterial hypertension, DM, obesity, and smoking.…”

Section: :4 M16mentioning

confidence: 99%

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Adverse effects of glucocorticoids: coagulopathy

Coelho

Santos

Neto

et al. 2015

European Journal of Endocrinology

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Hypercortisolism is associated with various systemic manifestations, including central obesity, arterial hypertension, glucose intolerance/diabetes mellitus, dyslipidemia, nephrolithiasis, osteoporosis, gonadal dysfunction, susceptibility to infections, psychiatric disorders, and hypercoagulability. The activation of the hemostatic system contributes to the development of atherosclerosis and subsequent cardiovascular morbidity and mortality. Previous studies have identified an increased risk of both unprovoked and postoperative thromboembolic events in patients with endogenous and exogenous Cushing's syndrome (CS). The risk for postoperative venous thromboembolism in endogenous CS is comparable to the risk after total hip or knee replacement under short-term prophylaxis. The mechanisms that are involved in the thromboembolic complications in hypercortisolism include endothelial dysfunction, hypercoagulability, and stasis (Virchow's triad). It seems that at least two factors from Virchow's triad must be present for the occurrence of a thrombotic event in these patients. Most studies have demonstrated that this hypercoagulable state is explained by increased levels of procoagulant factors, mainly factors VIII, IX, and von Willebrand factor, and also by an impaired fibrinolytic capacity, which mainly results from an elevation in plasminogen activator inhibitor 1. Consequently, there is a shortening of activated partial thromboplastin time and increased thrombin generation. For these reasons, anticoagulant prophylaxis might be considered in patients with CS whenever they have concomitant prothrombotic risk factors. However, multicenter studies are needed to determine which patients will benefit from anticoagulant therapy and the dose and time of anticoagulation.

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Section: :4 M16mentioning

confidence: 98%

Section: Figurementioning

confidence: 99%

Section: Hypercoagulabilitymentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: :4 M16mentioning

confidence: 99%

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Adverse effects of glucocorticoids: coagulopathy

Coelho

Santos

Neto

et al. 2015

European Journal of Endocrinology

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Hemostatic balance between pro‐ and anticoagulant is maintained during glucocorticoid treatment

Yamashita,

Nagae,

Umezawa

et al. 2023

Pediatric Blood & Cancer

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BackgroundGlucocorticoids are associated with an increased risk of venous thrombosis. Glucocorticoid treatment increases coagulation factor and anticoagulant levels; however, its effect on hemostatic function remains unclear. This study aimed to investigate the changes in comprehensive coagulation profiles after glucocorticoid treatment in noninflammatory diseases to elucidate the direct contribution of glucocorticoids to hemostatic function.ProcedurePatients diagnosed with primary immune thrombocytopenia requiring glucocorticoid treatment were prospectively enrolled in this study. Changes in coagulation factors and anticoagulants during glucocorticoid treatment and changes in thrombin generation potential were determined in the absence and presence of soluble thrombomodulin (sTM).ResultsSeven treatment cases (four for steroid pulse therapy and three for oral glucocorticoid therapy) in six patients with immune thrombocytopenia were examined. After glucocorticoid treatment, activated partial thromboplastin time significantly shortened, and activities of factor VIII, IX, XI, and XII significantly increased, except for von Willebrand factor antigen. Moreover, antithrombin and protein C (PC) activities significantly increased after glucocorticoid treatment. Two major parameters of thrombin generation potential, endogenous thrombin potential (ETP) and peak thrombin (Peak), significantly increased in the absence of sTM after glucocorticoid treatment. However, no significant increases in either parameter were observed in the presence of sTM. ETP‐TM and Peak‐TM ratios, which represent resistance to the anticoagulant effect of the PC pathway, significantly decreased after glucocorticoid treatment, suggesting that anticoagulant function via the PC pathway is elevated after glucocorticoid treatment.ConclusionsAs glucocorticoids increase intrinsic coagulation factor and anticoagulant levels, hemostatic balance between pro‐ and anticoagulant functions is maintained.

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Minimizing Cardiometabolic Risk Factors and Other Complications in Patients with Cushing’s Syndrome and Disease

Blount

Silverstein

2022

Pituitary Disorders Throughout the Life Cycle

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Perioperative thromboprophylaxis in Cushing’s disease: What we did and what we are doing?

Cited by 49 publications

References 31 publications

Adverse effects of glucocorticoids: coagulopathy

Adverse effects of glucocorticoids: coagulopathy

Hemostatic balance between pro‐ and anticoagulant is maintained during glucocorticoid treatment

Minimizing Cardiometabolic Risk Factors and Other Complications in Patients with Cushing’s Syndrome and Disease

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