Tissue factor coagulation pathway and blood cells activation state in renal insufficiency.

INTRODUCTION: Atherosclerotic cardiovascular disease is the leading cause of the increased morbidity and mortality observed in uremic patients. Thrombosis is an important contributor to the evolution of atherosclerotic lesions. The physiologically-relevant blood clotting depends on binding of activated factor VII (FVIIa) to exposed tissue factor (TF) on activated/damaged cells. MATERIALS AND METHODS: A cross-sectional study was performed on three age- and sex-matched groups of individuals: one group of 50 patients on maintenance hemodialysis (D group), one of 50 patients with a non-dialysed renal insufficiency (ND group) and one of 50 healthy controls (HC group). We studied basal plasma concentrations of FVIIa, factor VII-related antigen (FVIIAg), soluble TF, tissue factor pathway inhibitor (TFPI), TF-dependent circulating monocytes procoagulant activity (TF-dMPA), tissue factor-dependent plasma reactivity to activated protein C (TF-aPC), D-dimers (D-Di), and circulating markers of cellular activation/injury: soluble thrombomodulin (sTM), circulating microparticles (microP), soluble leukocyte, endothelial and platelet selectins (sL-selectin, sE-selectin, sP-selectin), soluble intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (sICAM-1 and sVCAM-1). Their variations induced, in hemodialysis patients, by a dialysis run were thereafter studied RESULTS: Values of FVIIa, FVIIa/FVIIAg ratio, sTF, TFPI, TF-dMPA, D-Di, sTM, microP, sL, sE and sP selectins, sICAM-1 and sVCAM-1 increased all along the hierarchy HC group/ND group/D group. Microparticles were mainly of platelet origin, to a lesser extent of monocyte origin. Dialysis induced an increase of FVIIa, sTF, TF-dMPA and circulating markers of cellular activation/injury. Strong correlations were observed between FVIIa/FVIIAg ratio and serum creatinine levels, sTF, TF-dMPA, sTM, sE-selectin, sVCAM-1. The TF-aPC was impaired in the ND and the D group, and the lower values were, in the D group, associated with antecedents of vascular access thrombosis. CONCLUSION: Renal insufficiency is associated to an activation of the tissue factor coagulation pathway, to a platelet, monocyte and endothelial activation/injury and to a deficient tissue-factor induced response to activated protein C which culminate in end-stage disease and are increased by hemodialysis runs. This contributes to linked coagulation and cellular conditions for an enhanced atherosclerosis progression. Due to the TF pathway activation, the therapeutic use of recombinant TFPI should be evaluated.

Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients.

Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis.

The anatomical value of technetium-thallium subtraction scanning in detection and location of parathyroid adenomas.

99mTechnetium-201Thallium subtraction scanning was performed in 24 patients with primary (N = 5) and secondary (N = 19) hyperparathyroidism. The preoperative scintigraphy (N = 12) detected 21 of 23 enlarged glands surgically removed and was helpful for detecting abnormal location especially in the mediastinum. Postoperative scanning in patients with recurrent hyperparathyroidism confirmed the excessive growth of the remaining half parathyroid after subtotal parathyroidectomy or a missing fifth parathyroid after total parathyroidectomy and autotransplantation. False negative results were due to tumor hyperplasia. The technique is recommended prior to repeated exploration in patients presenting persistent disease to predict the location of adenomas generally unsuccessfully detected by ultrasonography and computed tomography.