U. Haddeland et al., STIMULATING EFFECT ON TISSUE-TYPE PLASMINOGEN-ACTIVATOR - A NEW AND SENSITIVE INDICATOR OF DENATURED FIBRINOGEN, Thrombosis research, 77(4), 1995, pp. 329-336
A high clottability and a short thrombin clotting time have routinely
been considered as evidence of genuineness of the fibrinogen molecule.
Since denatured fibrinogen stimulates the t-PA-catalysed conversion o
f plasminogen to plasmin, it was of interest to study the sensitivity
of t-PA-stimulation as evidence of fibrinogen denaturation. Therefore,
fibrinogen was intentionally exposed to various denaturating conditio
ns (freeze-drying, heating, EDTA, alkali), and the clottability, the t
hrombin,clotting time and the t-PA-stimulating effect were recorded. W
e found that the clottability was a poor indicator of fibrinogen denat
uration, whereas the t-PA-stimulating effect could detect even mild fi
brinogen denaturation. The thrombin clotting time was shortened after
freeze-drying or heating at 47 degrees C, in spite of what might have
been expected. Thus, denaturation is not necessarily accompanied by a
prolonged clotting time. In some instances therefore, the t-PA-stimula
tion is an even more sensitive and reliable indicator of fibrinogen de
naturation than is the thrombin clotting time. Consequently, this para
meter should be combined with the thrombin clotting time to characteri
se preparations of fibrinogen.