P. Kallis et al., APROTININ INHIBITS FIBRINOLYSIS, IMPROVES PLATELET-ADHESION AND REDUCES BLOOD-LOSS - RESULTS OF A DOUBLE-BLIND RANDOMIZED CLINICAL-TRIAL, European journal of cardio-thoracic surgery, 8(6), 1994, pp. 315-322
The present recommendation is that aprotinin should be started before
cardiac surgery, but as bleeding is only a problem in a minority, most
patients are treated unnecessarily. In a prospective, randomised, dou
ble-blind trial we have studied the use of aprotinin, given only to th
e minority of patients who bled significantly post-operatively and who
had not received prophylactic aprotinin. Sixty patients, who bled in
excess of 400 ml in the first 3 h post-operatively were randomised to
receive either aprotinin (2 x 10(6) KIU loading dose followed by an in
fusion of 0.5 x 10(6) KIU/h for 4 h) or placebo, in addition to conven
tional treatment. The demographic characteristics and the surgical pro
cedures performed were similar in the two groups. Haematological varia
bles were measured (A) before and (B) at the end of the infusion. Thre
e patients were re-explored for excessive bleeding in each group and o
ne patient died in each group. The patients in the aprotinin group ble
d significantly less and had higher haemoglobin levels on discharge th
an the patients in the placebo group. The tissue plasminogen activator
antigen decreased and the fibrinogen level increased in the aprotinin
group. In addition, aprotinin increased the number of surface GPIb pl
atelet receptors as estimated by flow cytometry (36% versus 5%, P < 0.
01) and maintained the platelet von Willebrand Factor activity (vWF).
There was no significant difference in D-dimers, fibrin(ogen) degradat
ion products, plasma vWF activity and antigen, platelet vWF antigen, p
latelet aggregation (to collagen, arachidonic acid, platelet activatin
g factor and ristocetin), platelet count or transfusion of blood produ
cts between the two groups. Post-operative aprotinin reduces blood los
s, inhibits fibrinolysis and replenishes platelet GPIb receptors and v
WF activity, the components of platelet adhesion.