Aprotinin reduces cardiopulmonary bypass-induced blood loss and inhibits fibrinolysis without influencing platelets
Orchard MA, Goodchild CS, Prentice CR, Davies JA, Benoit SE, Creighton-Kemsford LJ, Gaffney PJ, Michelson AD
British Journal of Haematology. 1993;85((3):):533-41.
Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced blood loss. A double-blind study was carried out comparing aprotinin with placebo in patients undergoing re-operation for heart valve replacement. The results confirm that aprotinin is effective at reducing such loss. In the placebo treated group, significant increases were observed, during CPB, in the plasma concentrations of fibrinolytic activity, tissue plasminogen activator antigen, D-dimer, and beta-thromboglobulin. Platelet counts fell within 5-10 min of the patients going onto CPB, but this could be accounted for by the dilutional effect of the extracorporeal circuit. Inhibition of responsiveness of platelets, as judged by aggregometry, was significant only at the end of bypass when collagen was the agonist and after protamine reversal when ristocetin was the agonist. CPB did not enhance the release, into the circulation, of glycocalicin (a proteolytic fragment of glycoprotein Ib). In the aprotinin-treated group, the formation of fibrin degradation products as measured by D-dimer was inhibited. However, aprotinin did not influence the change in platelet count, suppress beta-thromboglobulin release from platelets, prevent the inhibition of platelet function or influence the concentration of plasma glycocalicin during the study period. These observations confirm that CPB leads to a fibrinolytic state and less responsive platelets. This study also indicates that aprotinin-induced reduction in blood loss is associated with inhibition of plasmin-mediated fibrin digestion and that the mechanism by which aprotinin reduces blood loss is not via protection of platelets during CPB.
The incidence of deep vein thrombosis in prostatectomised patients following the administration of the fibrinolytic inhibitor, aminocaproic acid (EACA)
Sinclair J, Forbes CD, Prentice CR, Scott R
Urological Research. 1976;4((3):):129-31.
Forty patients undergoing prostatectomy for benign prostatic hypertrophy were included in a double blind trial of epsilon aminocaproic acid, and the incidence of postoperative deep vein thrombosis determined, using 125I-fibrinogen technique. There was no significant difference between the groups, the overall incidence of abnormal scans being 50 per cent, but of the patients undergoing enucleative prostatectomy 68 per cent developed significant scan findings compared with 33 per cent following transurethral surgery.
Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease
Forbes CD, Barr RD, Reid G, Thomson C, Prentice CR, McNicol GP, Douglas AS
British Medical Journal. 1972;2((5809):):311-3.
In a double-blind trial tranexamic acid (AMCA, Cyclokapron), 1 g three times a day for five days, significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease. No side effects were seen in either group of patients. Screening tests showed no toxic action of tranexamic acid on the liver, kidney, or heart.