thromboxane-b2 and Cushing-Syndrome

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.

Topics: Blood Coagulation Disorders; Cushing Syndrome; Factor VIII; Fibrinogen; Glucocorticoids; Humans; Thrombocytosis; Thromboxane B2; Venous Thromboembolism; von Willebrand Factor

Cushing Syndrome (CS) is implicated by increased cardiovascular risk (CVR) leading to increased morbidity and mortality. Oxidative stress (OS) and platelet activation (PA) are associated with increased CVR. However, scarce data of OS in CS exist. Our objective was to determine the oxidant-antioxidant balance in CS.. Fourteen patients with CS at diagnosis and fourteen healthy subjects (NS) were evaluated OS by measuring plasma 15-F2t -Isoprostane (15-F2t -IsoP), PA by thromboxaneB2 levels (TXB2 ), and antioxidant reserve measuring total antioxidant capacity (TAC) and serum vitamin E.. 15-F2t -IsoP and TXB2 levels were significantly higher (P < 0·01) in CS, while vitamin E levels were higher in NS (P < 0·03). 15-F2t -IsoP levels were significantly higher (P < 0·01) in complicated vs not-complicated CS and NS and significantly higher (P < 0·03) in CS not-complicated vs NS. TXB2 levels were significantly reduced (P < 0·03) in NS vs complicated and not-complicated CS. A negative correlation between Vitamin E and UFC was observed in CS (P < 0·05 r = -0·497). TXB2 correlated with glucose, HbA1c and T-score (P < 0·05 r = 0·512, P < 0·03 r = 0·527 and P < 0·01 r = 0·783, respectively) and HDL (P < 0·01 r = -0·651). 15-F2t -IsoP correlated with triglicerides, HbA1c and diastolic pressure (P < 0·01 r = 0·650, P < 0·03 r = 0·571 and P < 0·05 r = 0·498, respectively) and HDL (P < 0·03 r = -0·594).. This study emphasizes the major role of OS in CS. As our findings demonstrated that enhanced OS and PA take place in this rare metabolic disorder which is associated with increased CVR, it could be suggested that these biochemical alterations can further contribute in the pathogenesis of atherosclerosis, increased CVR and mortality in CS.

Topics: Adult; Anthropometry; Antioxidants; Atherosclerosis; Cardiovascular Diseases; Cushing Syndrome; Female; Glucose; Hormones; Humans; Isoprostanes; Male; Middle Aged; Oxidants; Oxidative Stress; Platelet Activation; Thromboxane B2; Vitamin E

We have studied haemostatic parameters in 12 patients with Cushing's syndrome. Three patients had prolonged bleeding times, and in all seven patients whose bleeding times were measured 3-6 months after surgical treatment the postoperative bleeding times were shorter (mean 7.5 min) than the pretreatment times (mean 12.3 min). In ADP- or adrenaline-induced aggregation the second wave was lacking in six and the degree of aggregation was borderline or subnormal in five patients. One patient had, in addition, a severe defect in collagen-induced aggregation. However, thromboxane B2 production of the platelets from both endogenous and exogenous arachidonic acid was unaffected. Factor VIII:C, RAg and Rcof activities were all elevated, and in patients with severe disease F VIIIR:Ag and F VIII:Rcof activities were markedly more elevated than F VIII:C activity. The changes in both primary haemostasis and in factor VIII activities correlated clearly with the clinical severity of the disease.

Topics: Adolescent; Adult; Bleeding Time; Blood Platelets; Cushing Syndrome; Female; Hemostasis; Humans; Male; Platelet Aggregation; Thromboxane A2; Thromboxane B2; Thromboxanes