Further Studies on the Hypercoagulable State of Patients with Cushing’s Syndrome

The hemostatic balance is a complex system where the delicate equilibrium is regulated by several factors, including hormones. This review summarizes current knowledge of the effects of most frequent endocrine and metabolic diseases (such as hypothyroidism, hyperthyroidism, Cushing's syndrome, GH-related pituitary dysfunctions, pituitary prolactin-producing adenomas, polycystic ovary syndrome, primary hyperparathyroidism, and metabolic syndrome) on coagulation and fibrinolysis. Overt hypothyroidism appears to be associated with a bleeding tendency, whereas all other endocrine diseases appear to be associated with a thrombotic tendency. Globally, the disorders of coagulation and fibrinolysis usually range from mild to moderate, and, rarely, to severe laboratory abnormalities (for example, bleeding diathesis in overt hypothyroidism mainly due to an acquired von Willebrand's disease type 1). Further larger and high-quality studies are needed to provide more definitive information on the effects of endocrine disorders on coagulation and fibrinolysis.

Section: Cushing's Syndromementioning

confidence: 80%

Hemostatic abnormalities in endocrine and metabolic disorders

Franchini¹,

Lippi²,

Manzato³

et al. 2010

“…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%

“…Recent clinical studies have indicated various abnormalities in coagulation and fibrinolysis parameters in patients with endogenous (5,6,7) and exogenous hypercortisolism (8,9,10) that contribute to the development of thromboembolic events, atherosclerosis (11), and subsequent cardiovascular morbidity and mortality (12,13,14).…”

Section: Introductionmentioning

confidence: 99%

Adverse effects of glucocorticoids: coagulopathy

Coelho

Santos

Neto

et al. 2015

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.

“…Moreover, it has been demonstrated that CS is associated with a hypercoagulable state and increased incidence of venous thromboembolic events (VTE) (5)(6)(7)(8)(9). Some studies showed a shortening of the activated partial thromboplastin time (aPTT) (10)(11)(12) and elevated levels of factor VIII (F8), factor IX (F9) and von Willebrand factor (VWF) in CS with a consequent increased prevalence of cardiovascular disease such as ischaemic disease, cerebrovascular disease, vascular peripheral and lung disorders (10)(11)(12)(13)(14)(15)(16)(17)(18). Patients with CS also showed an impairment of the fibrinolytic system due to an excess of the fast-activating plasminogen activator inhibitor 1 (PAI-1 or SERPINE1) (19).…”

Section: Introductionmentioning

confidence: 99%

Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing's syndrome: results from a prospective study before and after surgery

Manetti

Bogazzi

Giovannetti

et al. 2010

112

118

Objectives: To evaluate whether patients with Cushing's syndrome (CS) had i) changes in coagulative and fibrinolytic parameters associated with CS activity and ii) higher prevalence of venous thromboembolic events (VTE). Design: Prospective study conducted on patients with CS evaluated at diagnosis and 12 months after surgery. Patients and methods: Forty patients with active CS (36 with Cushing's disease (CD) and 4 with an adrenal adenoma) were evaluated. Forty normal subjects and 70 patients with non-ACTH-secreting pituitary adenomas served as controls. All patients and controls underwent an assessment of coagulation and fibrinolysis indexes before and after surgery. Results: CS patients at baseline had a hypercoagulative phenotype when compared with normal subjects (activated partial thromboplastin time (aPTT), fibrinogen, D-Dimer, von Willebrand factor (VWF), plasminogen activator inhibitor 1 (PAI-1 or SERPINE1), antithrombin III (ATIII or SERPINC1), P!0.0001, a 2 antiplasmin, PZ0.0004, thrombin-antithrombin complex (TAT), PZ0.01, factor IX (F9), PZ0.03). Patients with still active disease after surgery had higher coagulative parameters than those in remission (VWF (P!0.0001), PAI-1 (PZ0.004), TAT (PZ0.0001), ATIII (PZ0.0002) and a 2 antiplasmin (or SERPINF2; PZ0.006)), whereas aPTT levels (PZ0.007) were significantly reduced. VTE occurred in three patients with CD (7.5%): one had a pulmonary embolism and two patients had a deep venous thrombosis; no patients submitted to transsphenoidal surgery for non-Cushing's pituitary adenoma had VTE (PZ0.04). Conclusions: Patients with CS have a procoagulative phenotype due to cortisol-associated changes in haemostatic and fibrinolytic markers, leading to increased incidence of VTE. Thromboprophylaxis seems to be appropriated in patients with active disease, particularly in the postoperative period.