Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome

Abstract

<jats:title>Summary</jats:title><jats:p>Recent studies showed that an imbalance of prothrombotic and antithrombotic factors and impaired thrombolytic activity contribute to the thrombophilia of the nephrotic syndrome (NS). However, it is not clear whether blood cell injury and/or activation is involved in hypercoagulability in NS patients. Our objectives were to study the increase in microparticle (MP) release and phosphatidylserine (PS) exposure on the outer membrane of MP-origin cells in NS patients, and to evaluate their procoagulant activity (PCA). The subjects were patients with membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS) and healthy controls. Analyses of MPs and PS exposure were performed using a flow cytometer. PCA was determined by clotting time and purified coagulation complex assays. We found that lactadherin+ MPs, which derived from red blood cells (RBC), platelet and endothelial cell, increased in NS patients. Moreover, PS exposure on RBCs and platelets in each NS group, especially in MN, are higher than that in controls. MP shedding and PS exposure of RBCs/platelets were highly procoagulant in NS patients. However, blockade of PS with lactadherin inhibited over 90% of PCA while an anti-tissue factor antibody had no significant inhibition effect. Our results demonstrate that the thrombophilic susceptibility of NS may be partly ascribed to MP release and PS exposure of RBCs, platelets and endothelial cells. Lactadherin is a sensitive probe for PS that has high anticoagulant activity.</jats:p>

Extracellular Vesicles in Renal Diseases

“…74 In a study of a heterogeneous group of patients with chronic renal failure and those on peritoneal dialysis and hemodialysis, all patients compared with healthy controls had higher levels of endothelial-derived microparticles (EMPs) and MPs of leukocyte origin. 75 This is in line with other studies.…”

Characterization of platelet aminophospholipid externalization reveals fatty acids as molecular determinants that regulate coagulation

“…In recent years it has been described as detecting PS exposure, although several annexins also bind PE (6,(9)(10)(11)(12)(13). Other proteins that indirectly measure APL exposure include lactadherin and cinnamycin, reported as specific PS or PE indicators, respectively (14)(15)(16).…”

Extracellular vesicles as mediators of vascular inflammation in kidney disease

“…These have recently been reviewed and will therefore only been referred to in relation to vascular leukocytes in this manuscript [116119] . However, it is of note that EV phosphatidylserine surface expression as a prothrombotic mediator was significantly increased in patients with the nephrotic syndrome of different etiologies [120] and the in vitro procoagulant effect of EVs from both hemodialysis and peritoneal dialysis patients was enhanced [46] .…”