 - Uremic toxins The importance of circulating toxins is suggested by the often beneficial effect of acute dialysis on platelet dysfunction, although the bleeding time is rarely normalized. In addition, raising the BUN to 60 to 120 mgdL by dietary manipulation can diminish platelet adhesiveness and prolong the bleeding time in some normal subjects. Urea alone, however, is probably not the major platelet toxin and there is no predictable correlation between the BUN and the bleeding time in patients with renal failure. Other potential toxins include guanidinosuccinic acid, phenolic acid, and middle molecules mol wt 500 to 3000 daltons. In vitro studies in which normal platelets are incubated with uremic serum suggest that a dialyzable factor interferes with the binding of fibrinogen to the platelet glycoprotein GP IIbIIIa receptor. In addition, uremic platelets are unable to adequately increase the expression of GP IIbIIIa and P-selectin in response to stimulation. 