Total and free protein S in nephrotic syndrome

Voisin²,

et al. 1994

Nephron

Disturbances in hemostatic and hemorheological parameters have been investigated in a group of 29 children with nephrotic syndrome: 23 children classified as steroid-sensitive and 6 as steroid-resistant. Studies were performed before prednisone treatment and 3 weeks later, after initiation of steroid therapy. Before treatment, the alterations in hemostatic system involved moderate thrombocytosis with spontaneous aggregation in 19 patients. High levels of fibrinogen, factor VIII, Willebrand factor, protein C, protein S and α₂-macroglobulin (α₂M) were observed. Factor XII and α₁-antitrypsin (α₁AT) were lower than normal. Antithrombin III (ATIII) level was normal in the majority of patients. A plasma and blood hyperviscosity syndrome was also observed as well as an increase in erythrocyte aggregation. During treatment, an improvement in the hemostatic parameters was observed in the patients who responded to prednisone. The expected increase in factor VIII (frequently described in the literature) was not observed, while there was a significant increase in protein C. In the steroid-resistant patients, the only significant changes observed were decreased fibrinogen and increased protein C. The hemorheological parameters showed a tendency towards normality regardless of whether or not the treatment provided remission of NS. The relationship between hemorheological and hemostatic factors changes are discussed.

Section: Discussionsupporting

confidence: 80%

Hemorheological and Hemostatic Parameters in Children with Nephrotic Syndrome Undergoing Steroid Therapy

Voisin²,

et al. 1994

Nephron

“…Previous reports from our institution [9,15] as well as those of others agree on the elevation of levels of the natural anticoagulants, proteins C and S, in childhood nephrotic syndrome, particularly during the relapse phase of the disease, when the prothrombotic haemostatic changes are at their highest [1][2][3][4][5][6][7][16][17][18].…”

Section: Discussionmentioning

confidence: 92%

“…Despite some disagreements, the weight of evidence was in favour of the elevation of the natural anticoagulants, proteins C and S, in childhood nephrotic syndrome [5][6][7][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Tissue factor pathway inhibitor in childhood nephrotic syndrome

et al. 2006

It is now recognised that the extrinsic tissue factor pathway is the main trigger to the coagulation system in vivo. Its main inhibitor, tissue factor pathway inhibitor (TFPI), has never been studied in childhood nephrotic syndrome. The aim of the study was to monitor the level of TFPI in childhood nephrotic syndrome. One hundred and thirty-nine nephrotic children were classified into the following groups: group 1 (n=25), in relapse and receiving no treatment; group 2 (n=37), in relapse but receiving steroid treatment; group 3 (n= 45), in early remission and on steroids; group 4 (n=24), in established remission and receiving no steroids; group 5 (n=8), steroid-resistant. The controls (n=84) were healthy and age-matched. There was significant elevation of total TFPI levels in groups 1 and 2 and 3; levels were comparable to those of the healthy controls in group 4. The highest levels of total TFPI were recorded in group 5. Like total TFPI, the levels of the free form of TFPI showed a statistically significant increase in groups 1, 2, 3 and 4, when compared with levels in healthy controls. The highest levels of free TFPI were recorded group 5. We concluded that the elevated levels of both the total and free TFPI in various phases of nephrotic syndrome add another natural anticoagulant mechanism, which will attenuate the hypercoagulability of childhood nephrotic syndrome.

“…Recent studies of nephrotic pa tients reported changes in plasma protein C, a vitamin-K-dependent natural anticoagulant that inactivates fac tors V and VIII, and in plasma protein S, the cofactor of protein C [25]. Absolute plasma levels of both protein C and protein S antigens were found elevated in three stud ies [20,26,27], while in one study protein C antigen was found normal [19], However, because of both increased plasma concentration of C4b-binding protein, with which protein S forms a complex, and urinary losses, free (active) protein S may be reduced [26,27], Besides, specific activity of free protein S. i.e. the ratio of its anti coagulant activity to its antigen level, was decreased [26], while specific activity of protein C was either nor mal [22] or decreased [26].…”

Section: Abnormalities Of Coagulation and Fibrinolysis Factors In Sysmentioning

confidence: 99%

Coagulation Factors in Nephrotic Syndrome

Kanfer¹

1990

Am J Nephrol

Nephrotic syndrome (NS) is associated with several disorders of hemostasis: thrombocytosis and platelet hyperaggregability; increased plasma levels of factors V and VIII, and of fibrinogen with blood hyperviscosity; decreased plasma levels of natural anticoagulants: free protein S, and antithrombin III compensated by increased levels of α₂-macroglobulin; lowered fibrinolytic activity. Intensity of hypercoagulability is related to the degree of hypoalbuminemia; however, the role of hypercoagulability in the increased incidence of thromboembolic events, including renal vein thrombosis, is not proved. Clotting disorders are due to urinary losses of anticoagulants or to increased liver synthesis of procoagulants stimulated by hypoalbuminemia. Moreover, changes in clotting factors levels may be due to intravascular thrombin formation (marked by increased plasma levels of fibrinopeptide A). During active phases of glomerulonephritides (GN) with NS, thrombin formation might in fact arise in glomeruli, following activation of the glomerular hemostasis system. Isolated glomeruli from human crescentic GN, rabbit nephrotoxic GN and rat HgCl₂ autoimmune GN produce excessive amounts of procoagulant (tissue factor) activity (PCA). Sequential studies of the self-limited HgCl₂ GN showed that glomerular PCA, proteinuria and glomerular fibrin deposits peaked concomitantly at the acme of the disease, suggesting that immunologically mediated glomerular damage had triggered the extrinsic coagulation pathway.