Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism

Abstract

Background and objectives: Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality and morbidity. Little is known about hemostatic features of patients with PHPT. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patints have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between serum calcium and PTH and these hemostatic parameters in patients with PHPT. Design and methods: Twenty-four patients with PHPT and 20 age-, sex-, and-weight-matched healthy controls were included in the study. Tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-1 (PAI-1), TFPI, and TAFI were measured. The relationships between serum calcium, phosphorus, and PTH and these hemostatic parameters were examinated. Results: Compared with the control subjects, t-PA, PAI-1, and PAI-1/t-PA ratios were significantly increased in patients with PHPT (P!0.0001), whereas TFPI levels were significantly decreased (P!0.0001). Plasma TAFI Ag levels did not significantly change in patients with PHPT compared with the controls. In patients with PHPT, serum phosphorus was negatively correlated with plasma PAI-1 Ag levels and PAI-1/t-PA ratio (r: K0.453, P!0.05; r: K0.580, P!0.01 respectively). There was a positive correlation between Cl/P ratio and plasma PAI-1 levels and PAI-1/t-PA ratio (r: 0.434, P!0.05; r: 0.528, P!0.05 respectively). iPTH was positively correlated with plasma PAI-1/t-PA ratio (r: 0.429, P!0.05). Interpretation and conclusions: In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased PAI-1, PAI-1/t-PA ratios and decreased TFPI levels in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality due to cardiovascular disease seen in patients with PHPT.

Hemostatic abnormalities in endocrine and metabolic disorders

“…Erem et al reported that 24 patients with symptomatic PHPT had significantly higher plasma levels of t-PA and PAI-1, and lower TFPI levels than those in 20 age-, sex-and body weight-matched controls (116). Moreover, serum parathyroid hormone (PTH) levels were positively associated with plasma PAI-1 levels in PHPT patients (116).…”

“…Erem et al reported that 24 patients with symptomatic PHPT had significantly higher plasma levels of t-PA and PAI-1, and lower TFPI levels than those in 20 age-, sex-and body weight-matched controls (116). Moreover, serum parathyroid hormone (PTH) levels were positively associated with plasma PAI-1 levels in PHPT patients (116). In a previous article, the same authors found increased platelet count, higher activities of factor VII and IX, and increased levels of D-dimer in 23 PHPT patients compared with healthy controls, whereas no significant differences were found in plasma fibrinogen, VWF, factor V, factor IX, antithrombin, protein C, protein S, t-PA, and PAI-1 between the two groups (117).…”

Thromboelastographic Profile of Patients with Hyperparathyroidism Secondary to Chronic Kidney Failure Submitted to Total Parathyroidectomy

“…As in primary hyperparathyroidism [8], hyperparathyroidism secondary to chronic kidney failure may be related to the prothrombotic thromboelastographic profile presented. While the traditional concern of anesthesiologists and surgeons during surgery on patients with chronic kidney failure is the possibility of greater surgical bleeding [9], clinical evidence has demonstrated that chronic kidney disease is also associated with blood clotting abnormalities that favor a pro-thrombotic hypercoagulable state [3][4][5]10], with an increased risk of thromboembolic phenomena that may increase with the decline in kidney function [3].…”

“…The mechanisms of the increase blood clotting in patients with chronic kidney failure that lead to thrombotic complications are less known and seem have a multi-factor nature [3,4]. It has recently been demonstrated that patients with primary hyperparathyroidism and normal kidney function have a hypercoagulable and hypofibrinolytic profile, which may contribute to an increased risk of atherosclerotic and atherothrombotic complications [8].…”

Association of serum calcium concentrations with fibrinogen and homocysteine in non-diabetic Korean subjects

“…[22] Calcium is an essential hemostatic cofactor and a ubiquitous second messenger involved in intracellular signaling throughout the entire body including the vascular system. Previously, a few studies showed increased platelet counts and coagulation factors [23,24] as well as increased plasminogen activator inhibitor-1 and decreased thrombinactivatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism, [25] suggesting that hypercalcemia induces hemostatic imbalance. Experimental hypercalcemia in rats results in a reduced clotting time, providing a physiological background Table 4 Multivariate linear regression analysis for Ca c and other clinical variables with fibrinogen and homocysteine as the dependent variables.…”