Abnormal fibrin clot architecture in nephrotic patients is related to hypofibrinolysis: influence of plasma biochemical modifications - A possible mechanism for the high thrombotic tendency?

Porosity, viscoelasticity and morphological properties of plasma fibrin fro m 16 nephrotic patients and 16 healthy volunteers were compared. Nephrotic patients were characterized by formation of tight and rigid plasma fibrin g els which resulted in a slower rate of fibrin lysis studied either under pr essure-driven permeation or diffusional transport of fibrinolytic agents. T hese latter findings indicated that both abnormal fibrin network conformati on and abnormal fibrin fiber structure were involved in hypofibrinolysis. A lbumin supplementation up to 40 mg/ml partially restored normal fibrin arch itecture and increased the rate of fibrinolysis in these patients. Multipar ametric analysis showed that nephrotic patients were mainly characterized b y a low plasma albumin level (R = -0.85), a low albumin to fibrinogen ratio (R = -0.89) and a high resistance to lysis (R = -0.82). High triglycerides level was the only plasma modification related to the slower fibrin lysis rate (R = -0.54). High fibrin rigidity (G') was the only fibrin parameter s imultaneously related to the nephrotic state (R = 0.75) and the lysis resis tance (R = -0.71). After eliminating the effects of age, albumin and fibrin ogen levels, low fibrin porosity (Ks) and low fiber mass-length ratio (mu) were the main features of the nephrotic state. These findings an discussed in relation to both the pathophysiology of thrombotic complications in neph rotic syndrome and their pharmacological prevention.