Rotation thromboelastometry and the hypercoagulable state in <scp>C</scp>ushing's syndrome

Coelho, Maria Caroline Alves; Neto, Leonardo Vieira; Kasuki, Leandro; Wildemberg, Luiz Eduardo; Santos, Camila Vicente dos; Castro, Gizele; Gouvêa, Glauber; Veloso, Orlando; Gadelha, Telma; Gadelha, Mônica R.

doi:10.1111/cen.12491

Cited by 17 publications

(25 citation statements)

References 31 publications

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“…We demonstrated that only the beginning of clot formation (the intrinsic pathway) is altered, and we found increased plasma levels of FVIII, vWF, and D-dimer and decreased activated partial thromboplastin time in patients with active CS. In addition, we observed an increased clot formation speed and higher clot strength in obese CS patients as compared to non-obese CS patients (37).…”

Section: Figurementioning

confidence: 53%

“…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%

“…Recently, our group studied hemostatic and thromboelastometric parameters in 30 patients with active CS and in 30 control subjects matched for age, sex, BMI, DM, arterial hypertension, ABO blood group, and smoking (37). Rotation thromboelastometry was used to evaluate the intrinsic, extrinsic, and fibrinogen pathways.…”

Section: Figurementioning

confidence: 99%

“…Of the 22 studies (5,6,7,9,14,15,30,32,33,34,35,36,37,38,39,40,44,47,48,49,50,51) that evaluated hypercoagulability in CS, few of them assessed the risk of thromboembolism in patients who received thromboprophylaxis (32,38,51). Prophylactic treatment appeared to besafe, seeing as no case of bleeding was reported in patients during anticoagulant treatment (54).…”

Section: Prophylaxis For Thromboembolism In Patients With Csmentioning

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: Figurementioning

confidence: 53%

Section: Hypercoagulabilitymentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Prophylaxis For Thromboembolism In Patients With Csmentioning

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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“…However, a reduction in activated partial thromboplastin time (aPTT), a marker of the intrinsic system, in CS has been repeatedly described (16,19,24,25,26,33,34,35). Recently, Gadelha et al…”

Section: Coagulation Cascadementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The spectrum of haemostatic abnormalities in glucocorticoid excess and defect

Isidori

Minnetti

Sbardella

et al. 2015

European Journal of Endocrinology

107

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Glucocorticoids (GCs) target several components of the integrated system that preserves vascular integrity and free blood flow. Cohort studies on Cushing's syndrome (CS) have revealed increased thromboembolism, but the pathogenesis remains unclear. Lessons from epidemiological data and post-treatment normalisation time suggest a bimodal action with a rapid and reversible effect on coagulation factors and an indirect sustained effect on the vessel wall. The redundancy of the steps that are potentially involved requires a systematic comparison of data from patients with endogenous or exogenous hypercortisolism in the context of either inflammatory or non-inflammatory disorders. A predominant alteration in the intrinsic pathway that includes a remarkable rise in factor VIII and von Willebrand factor (vWF) levels and a reduction in activated partial thromboplastin time appears in the majority of studies on endogenous CS. There may also be a rise in platelets, thromboxane B2, thrombin-antithrombin complexes and fibrinogen (FBG) levels and, above all, impaired fibrinolytic capacity. The increased activation of coagulation inhibitors seems to be compensatory in order to counteract disseminated coagulation, but there remains a net change towards an increased risk of venous thromboembolism (VTE). Conversely, GC administered in the presence of inflammation lowers vWF and FBG, but fibrinolytic activity is also reduced. As a result, the overall risk of VTE is increased in long-term users. Finally, no studies have assessed haemostatic abnormalities in patients with Addison's disease, although these may present as a consequence of bilateral adrenal haemorrhage, especially in the presence of antiphospholipid antibodies or anticoagulant treatments. The present review aimed to provide a comprehensive overview of the complex alterations produced by GCs in order to develop better screening and prevention strategies against bleeding and thrombosis.

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The Effect of Immunosuppression on Coagulation After Liver Transplantation

et al. 2019

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Everolimus (EVR) is a mammalian target of rapamycin (mTOR) inhibitor commonly used for immunosuppression (IS) after liver transplantation (LT). However, there are concerns about whether mTOR inhibitors may move the hemostatic balance toward a higher likelihood of thrombosis. The present study aimed to investigate potential coagulation disorders after the administration of EVR. We evaluated 54 patients after conversion to an EVR‐based IS regimen (n = 26) and compared those patients with patients who were switched to extended‐release tacrolimus (TAC) but had never received EVR (n = 28). At baseline and again at 1 month and 6 months after conversion, we measured international normalized ratio, activated partial thromboplastin time, and anticoagulation and fibrinolysis factors, and we performed rotational thromboelastometry (ROTEM). Data were analyzed with a Mann‐Whitney U test, a repeated‐measure analysis of variance, and a Fisher’s exact test. Statistical significance was set at the level of P ≤ 0.05. Plasma levels of von Willebrand factor, fibrinogen, and factor VIII were significantly higher than baseline levels at 1 month and 6 months after conversion of IS to EVR (P < 0.001); plasma levels of protein C, protein S, and plasminogen also increased significantly (P < 0.001). ROTEM confirmed a significant increase in maximum clot firmness in EXTEM, INTEM, and FIBTEM assays (P < 0.001). In all assays, maximum lysis was significantly lower than baseline levels at 1 month and 6 months after conversion to EVR. Patients converted to IS with extended‐release TAC exhibited no significant changes in coagulation variables. Retrospective analysis showed a significantly higher incidence of thromboembolic complications among patients treated with EVR‐based IS than among those treated with extended‐release TAC (P < 0.01). In conclusion, the administration of EVR after LT seems to modify hemostasis to a procoagulant state. Thrombophilia screening before conversion may determine which patients will benefit from conversion to EVR‐based IS.

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Rotation thromboelastometry and the hypercoagulable state in Cushing's syndrome

Abstract: Although FVIII and vWF were abnormal in CS patients, only the initiation clot formation was different in the ROTEM® methodology and no deep vein thrombosis was found.

Cited by 17 publications

References 31 publications

Adverse effects of glucocorticoids: coagulopathy

Adverse effects of glucocorticoids: coagulopathy

MECHANISMS IN ENDOCRINOLOGY: The spectrum of haemostatic abnormalities in glucocorticoid excess and defect

The Effect of Immunosuppression on Coagulation After Liver Transplantation

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