Stability of erythrocyte membrane and overall hemostasis potential - A biocompatibility study of mebrofenin and other iminodiacetic acid derivatives.

Abstract

Intravenous injection seems to be the most convenient way of administering drugs and contrast agents, which makes components of the blood the first and usually unwanted target of their action. Binding of intravenously administered compounds to erythrocytes, blood platelets and vascular wall may have serious clinical implications. The aim of this study was to examine the influence of four iminodiacetic acid derivatives, potential ligands for gadolinium complexation, on the process of coagulation and fibrinolysis, activity of thrombin and hemolysis. Kinetic parameters of coagulation and fibrinolysis process were determined during an optical CL-test based on measurement of transmittance alterations. Thrombin (0.5 IU/mL) and t-PA (240 ng/mL) were used to obtain a clotting and lysis curve. The activity of thrombin was determined with a chromogenic substrate S-2238. Hemolysis was examined spectrophotometrically and expressed as a percentage of released hemoglobin. Exposure to iminodiacetic acid derivatives resulted in a significant increase in the overall potential of clotting and lysis (CLAUC), as well as with the significant changes in the key parameters of these processes (thrombin time, initial plasma clotting velocity, clot stabilization time). Furthermore, iminodiacetic acid derivatives caused a significant decrease in the amidolytic activity of thrombin and enhanced hemolysis in a concentration-dependent manner. Despite their influence on the process of coagulation and fibrinolysis, amidolytic activity of thrombin and hemolysis, iminodiacetic acid derivatives should be generally considered safe as the significant effects were observed mostly at 4 μmol/mL, which is about 10-fold higher than the theoretical plasma concentration of these compounds.