Coagulation Profile Dynamics in Pediatric Patients with Cushing Syndrome: A Prospective, Observational Comparative Study

Birdwell, Leah; Lodish, Maya; Tirosh, Amit; Chittiboina, Prashant; Keil, Mark; Lyssikatos, Charlampos; Belyavskaya, Elena; Feelders, Richard A; Stratakis, Constantine A.

doi:10.1016/j.jpeds.2016.06.087

Cited by 10 publications

(6 citation statements)

References 20 publications

(25 reference statements)

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“…6,11,22 Several studies have identified peculiar alterations of coagulation and fibrinolysis in patients with endogenous hypercortisolism that may contribute to the development of thromboembolic events. 5,23 In particular, it has been hypothesized that a prothrombotic state may be fostered by increased levels of procoagulant factors such as factor (F) VIII 7,18,[24][25][26][27][28][29][30] and von Willebrand factor (VWF) 18,[25][26][27][31][32][33] levels, with a concomitant impaired fibrinolytic capacity, which mainly results from an elevation in plasminogen activator inhibitor 1 (PAI-1). 20,25,[27][28][29]31,34 Finally, Koutroumpi et al 35 confirmed the presence of a state of hypercoagulability in patients with Cushing's syndrome through an increase in thrombin generation, a global assay that measures the overall tendency of a plasma sample to form thrombin after initiation of coagulation.…”

Section: Effects Of Endogenous Hypercortisolism On Hemostasis: the Cushing's Syndrome Paradigmmentioning

confidence: 99%

Use of Glucocorticoids and Risk of Venous Thromboembolism: A Narrative Review

Simion

Campello

Bensi

et al. 2021

Semin Thromb Hemost

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Glucocorticoids are potent anti-inflammatory agents that are widely used for the treatment of many inflammatory, autoimmune, and neoplastic disorders. However, their beneficial effect is associated with several side effects, including an increased risk of cardiovascular complications, such as myocardial infarction and stroke. Whether their use also contributes to a procoagulant state, and therefore increases the risk of venous thromboembolism (VTE), is still a matter of debate. As an increased risk of venous thrombotic events is described in patients with Cushing's syndrome, which is characterized by endogenous hypercortisolism, it is reasonable to speculate that the chronic administration of glucocorticoids may induce a hypercoagulable state. However, it seems virtually impossible to separate the role of the drug from the underlying condition, which itself predisposes to the development of VTE. Actually, some evidence suggests that the use of exogenous glucocorticoids for the treatment of underlying disease and its exacerbations may further amplify the risk of VTE. Moreover, a procoagulant state has also been reported in healthy participants receiving oral glucocorticoids versus placebo. We have performed a concise narrative review on available data on the influence of exogenous glucocorticoids on hemostasis and their clinical impact on the risk of VTE.

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Section: Effects Of Endogenous Hypercortisolism On Hemostasis: the Cushing's Syndrome Paradigmmentioning

confidence: 99%

Use of Glucocorticoids and Risk of Venous Thromboembolism: A Narrative Review

Simion

Campello

Bensi

et al. 2021

Semin Thromb Hemost

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“…The physiological explanation to link hypercortisolism and hypercoagulability is not fully understood. In one study, level of factor VIII positively correlated with UFC levels (11, 58), (not observed in our meta-analysis). Obesity also confers a higher risk of VTE, but the risk in CS seems higher than in otherwise healthy obese patients who are at low risk (14).…”

Section: Discussionmentioning

confidence: 38%

Hypercoagulability and Risk of Venous Thromboembolic Events in Endogenous Cushing's Syndrome: A Systematic Meta-Analysis

et al. 2019

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Background: Hypercortisolism has been implicated in the development of venous thromboembolic events (VTE). We aimed to characterize VTE risk in endogenous Cushing's syndrome (CS) patients, compare that risk to other pathologies, and determine if there are any associated coagulation factor changes.Methods: Medline and Scopus search for “hypercortisolism” and “thromboembolic disease” from January 1980 to April 2017 to include studies that reported VTE rates and/or coagulation profile of CS patients. A systematic review and meta-analysis were performed.Results: Forty-eight studies met inclusion criteria. There were 7,142 CS patients, average age was 42 years and 77.7% female. Odds ratio of spontaneous VTE in CS is 17.82 (95%CI 15.24–20.85, p < 0.00001) when comparing to a healthy population. For CS patients undergoing surgery, the odds ratio (both with / without anticoagulation) of spontaneous VTE is 0.26 (95%CI 0.07–0.11, p < 0.00001)/0.34 (0.19–0.36, p < 0.00001) when compared to patients undergoing hip fracture surgery who were not treated with anticoagulants. Coagulation profiles in patients with CS showed statistically significant differences compared to controls, as reflected by increases in von Willebrand factor (180.11 vs. 112.53 IU/dL, p < 0.01), as well as decreases in activated partial thromboplastin time (aPTT; 26.91 vs. 30.65, p < 0.001) and increases in factor VIII (169 vs. 137 IU/dL, p < 0.05).Conclusion: CS is associated with significantly increased VTE odds vs. general population, but lower than in patients undergoing major orthopedic surgery. Although exact timing, type, and dose of anticoagulation medication remains to be established, clinicians might consider monitoring vWF, PTT, and factor VIII when evaluating CS patients and balance advantages of thromboprophylaxis with risk of bleeding.

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“…After initial studies that suggested presence of a hypercoagulable state in patients with Cushing’s syndrome ( 39 ), spontaneous activation of the hemostatic system was consistently shown in patients with hypercortisolism. Increased circulating levels of fibrinogen ( 19 , 20 , 40 , 41 ), D-dimer ( 20 , 23 , 40 ), vWF ( 20 , 42 – 44 ), AT-III ( 19 – 21 , 44 , 45 ), protein C-protein S complex ( 21 , 22 , 41 , 45 ), and PAI-1 ( 19 , 20 , 41 ) were reported together with changes of additional coagulation factors and hemostatic tests ( 19 – 21 , 41 , 43 , 46 ) in several cross-sectional comparisons of patients with Cushing’s syndrome with healthy subjects. Some studies suggested that these changes could be more relevant in patients with ACTH-producing adenomas ( 44 ) and increased levels of procoagulants and antifibrinolytics were reported also in children with Cushing’s syndrome that resolved after surgical treatment ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension

Brosolo,

Da Porto,

Bulfone

et al. 2024

Front. Endocrinol.

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Background and aimsA prothrombotic state was demonstrated in patients with Cushing’s syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension.MethodsIn 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol).ResultsPlasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function.ConclusionGreater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

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Coagulation Profile Dynamics in Pediatric Patients with Cushing Syndrome: A Prospective, Observational Comparative Study

Cited by 10 publications

References 20 publications

Use of Glucocorticoids and Risk of Venous Thromboembolism: A Narrative Review

Use of Glucocorticoids and Risk of Venous Thromboembolism: A Narrative Review

Hypercoagulability and Risk of Venous Thromboembolic Events in Endogenous Cushing's Syndrome: A Systematic Meta-Analysis

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension

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