FIBRINOGEN PRESENT IN EDTA-ANTICOAGULATED PLASMA STIMULATES THE TISSUE-TYPE PLASMINOGEN ACTIVATOR-CATALYZED CONVERSION OF PLASMINOGEN TO PLASMIN

The presence of soluble fibrin in plasma is an early and sensitive ind icator of activation of the coagulation system. Quantitative spectroph otometric assays for soluble fibrin can be based on the principle that soluble fibrin stimulates the tissue-type plasminogen activator-catal ysed conversion of plasminogen to plasmin. It was previously shown tha t treatment of purified fibrinogen by EDTA, which removes the three ti ghtly bound Ca2+ ions, results in exposure of tissue-type plasminogen activator-catalytic sites similar to those unveiled by thrombin. Since EDTA is a common anticoagulant, it was of interest to study the effec t of EDTA on a test based on plasminogen activation. It is concluded t hat the determination of soluble fibrin in EDTA-anticoagulated plasma from healthy individuals gives a false positive indication of the pres ence of soluble fibrin. This was true irrespective of whether the test was performed at pH 7.4, 7.8 or 8.5. The most probable explanation is that tissue-type plasminogen activator-stimulating sites are exposed in fibrinogen by EDTA. Therefore, EDTA-plasma is unsuitable for assayi ng soluble fibrin with tests based on the tissue-type plasminogen acti vator-mediated conversion of plasminogen to plasmin.