DEXTRAN SULFATE ACTIVATION OF THE CONTACT SYSTEM IN PLASMA AND ASCITES

We have previously reported on the presence of proenzymes and inhibito rs of the contact system in ascitic fluid. Malignancy-related ascites was also found to contain both high and low molecular weight kininogen (HK and LK). On this basis we have studied a possible activation of t he contact system in ascites. Generation of amidolytic activity toward s the chromogenic substrate S-2302 after incubation with dextran sulph ate (DXS), was found in ascites from patients with gastrointestinal ca ncer, but not in ascites from patients with benign liver disease. It i s concluded that malignancy-related ascites allows contact activation to take place, while benign ascites does not. This activation process, generating bradykinin, could possibly be of relevance to the mechanis m of ascites generation. Plasma samples from patients with ascites wer e also tested in relation to activation of the contact system. Activat ion was evaluated by immunoblotting, studying the disappearance of int act HK after the initiation of activation with different concentration s of DXS. In control plasma, activation took place at low concentratio ns of DXS (25 - 50 mu g/ml). In plasma samples from patients with mali gnancy-related or benign ascites, contact activation was depressed. In some samples concentrations of DXS up to 1 mg/ml, were not able to ac tivate the contact system at all. Concentrations of proenzymes and rel evant inhibitors in the contact system, HK and total protein were also determined. We found the concentration of prekallikrein to be positiv ely correlated with the degree of activation. Concentrations of inhibi tors such as C1-inhibitor, did not show any correlation with activatio n.