Concentration of Three Thrombin Inhibitors in the Nephrotic Syndrome in Adults

Abstract

Plasma antithrombin III (AT III), α₁-antitrypsin (α₁-AT) and α₁-macroglobulin (α₁-M) concentrations were measured in 17 cases of the nephrotic syndrome (NS) in adults. The mean plasma level of AT III was normal. The AT III concentration was correlated with albuminaemia (r=+0.718, p < 0.005), cholesterolaemia (r= – 0.651, p < 0.005) as well as with urinary protein (r = – 0.531, p < 0.05). The α₁-AT concentration was decreased (p < 0.01) and correlated with serum albumin level (r = + 0.643, p < 0.01). The α₁-M concentration significantly increased (p < 0.001). A negative correlation of the α₁-M level with serum albumin concentration (r= -0.561, p < 0.025) and a positive correlation with the cholesterol concentration (r= +0.819, p < 0.001) was found. AT III and α₁-M were inversely correlated (r= –0.706, p < 0.005). It is considered that in NS in adults, the increase of α₁-M is not compensatory for AT III, and there is no objection to the use of heparin in thrombosis prophylaxis with the exception of a few cases with very low AT III levels.

Coagulation Factors in Nephrotic Syndrome

“…Plasma AT III, however, cor related positively with serum albumin level and nega tively with proteinuria in all studies [6,18,21,23], The relationship between AT III level and the intensity of NS protein disturbances might in part account for discre pant results of AT III measurements obtained at differ ent phases of NS in various studies. In contrast, plasma level of the second thrombin inhibitor, a 2-macroglobulin, is increased in NS [18,21], which can explain why total plasma antithrombin activity is enhanced [4,18]. These changes might have implications for anticoagu lant therapy because the competition between AT III (the cofactor of heparin) and ci2-macroglobulin for thrombin inactivation is modified in favor of the latter, and because heparin impairs antithrombin activity of a 2-macroglobulin [24].…”

“…Mean plasma AT III was found to be either low (less than 75-80% of normal value) [18,19] or nor mal [8,[20][21][22]; moreover, a variable proportion of ne phrotic patients, ranging from 7% [5] to 40% [22,23] or 60% [18] had low AT III. Plasma AT III, however, cor related positively with serum albumin level and nega tively with proteinuria in all studies [6,18,21,23], The relationship between AT III level and the intensity of NS protein disturbances might in part account for discre pant results of AT III measurements obtained at differ ent phases of NS in various studies. In contrast, plasma level of the second thrombin inhibitor, a 2-macroglobulin, is increased in NS [18,21], which can explain why total plasma antithrombin activity is enhanced [4,18].…”

Venous Thromboembolism in Patients with Membranous Nephropathy

“…This may represent differences in one of the many determinants of serum albumin, including nutritional status, inflammation, selectivity of protein permeability (22), or other unmeasured factors that may predispose patients to thrombosis. Additional mechanisms include the hepatic overproduction of fibrinogen and factors V and VIII as a compensatory response to hypoalbuminemia (23) and a deficiency in plasma antithrombin III shown to correlate with serum albumin level (24)(25)(26)(27)(28)(29)(30). Albumin is a cofactor for the binding of plasminogen to fibrin and their interaction with tissue plasminogen activator (31).…”

Chronic Kidney Disease Increases Risk for Venous Thromboembolism

“…Patients with CKD, particularly those with the nephrotic syndrome, have elevated blood levels of fibrinogen and inflammatory markers; however, these factors were not VTE risk factors in LITE. Patients with CKD and nephrotic syndrome may also have endothelial cell dysfunction, 14 enhanced platelet activation and aggregation, 15 activation of the coagulation system, 16,17 and decreased endogenous anticoagulants. 17,18 Larger studies, with data on proteinuria, are needed to evaluate the hemostatic mechanisms mediating the association between CKD and VTE.…”