Studies on Fibrinogen Fractions Isolated from Human Plasma by Precipitation with Cold Ether




Mackay, Maycock, Silk and Combridge (1965) have shown that human fibrinogen preparations isolated by cold ether from freshly collected plasma (fraction HAHG, rich in Factor VIII), or from outdated plasma (fraction ETF), generate, when incubated at 37°C., traces of kinin (2–30 μmg. of bradykinin per ml. of fraction in 60 minutes). Activation of the plasminogen in the two fractions enhances the kinin formation in HAHG (30–117 μmg./ml. per 60 minutes), but not in ETF. Longer incubation did not increase the kinin yield.

With larger transfusions, the amounts of kinin which develop in activated HAHG could be sufficient to produce pharmacological effects, and consequently clinical reactions (Mackay et al., 1965). However, there is no evidence that the plasminogen in transfused HAHG is activated in the body. Even if this were the case, the action of this enzyme on the kinin-yielding substrate (kininogen) in HAHG is so slow that the resulting kinin would be destroyed in vivo by the normal blood kininase (a carboxypeptidase), before effective levels could develop. The present work suggests that the occasional reactions to transfusions (Maycock, Evans, Vallet, Combridge, Wolf, MacGibbon, French, Wallett, Dacie, Biggs, Handley and Macfarlane, 1963) could be due to the presence in HAHG and ETF of already active kalli-krein which rapidly forms kinin by interacting with the high kininogen concentration in the recipient's plasma (cf. Fig. 1 in Mackay et al., 1965). The fractions also contain a factor capable of activating the kallikreinogen in the patient's plasma.

The nature of the enzymic contaminant in HAHG and ETF, which hydrolysed p-tosyl-l-arginine methyl ester (TAMe) even when the plasminogen in the two fractions had not been activated (Mackay et al., 1965), was also investigated in the present study.