Aprotinin: The ideal anti-coagulant?

A. Quereshi, J. Lamont, P. Burke, P. Grace, D. Bouchier-Hayes

Research output: Contribution to journalArticlepeer-review

Abstract

The serine proteinase inhibitor, aprotinin, significantly reduces transfusion requirements during open heart surgery. Whether this benefit is associated with an increased tendency to thrombosis has not been studied. We investigated the effect of aprotinin in an experimental arterial thrombosis model. In 17 male Sprague-Dawley rats, the infrarenal aorta was replaced with 1.0-mm diameter PTFE grafts of varying lengths. The time to graft occlusion, recorded by palpation, Doppler ultrasound and a distal bleeding test, was 20.2 ± 1.8 min, 35.8 ± 6.1 min and 43.7 ± 6.6 min for grafts of 10, 7.5 and 5.0 min respectively (r = -0.98, p < 0.05). Following PTFE graft placement 24 Sprague-Dawley rats were given saline (n = 6), aprotinin (n = 6), heparin (n = 6), and heparin + aprotinin (n = 6). The time to occlusion was significantly prolonged in the aprotinin group (71.7 ± 20.4 min vs. 20.2 ± 1.8 min, p < 0.05). The time to thrombosis for heparin + aprotinin and heparin alone was also significantly prolonged (p < 0.05). Prothrombin times (PT) were 21.9 ± 3.0s for control, 29.4 ± 6.2s for aprotinin, 40.7 ± 2.5s for heparin and 39.9 ± 14.5s for heparin + aprotinin (p < 0.05 vs. control for all values). Bleeding time was not prolonged with aprotinin (3.0 ± 0.9 min vs. 2.9 ± 0.7 min). The bleeding time was 18.9 ± 4.1 min for heparin + aprotinin and 22.5 ± 2.3 min for heparin alone (p < 0.05 vs. control for both values). This analysis demonstrates that high doses of aprotinin induce a significant anti-coagulant effect in a simple experimental thrombosis model. This effect is less than that seen with heparin and is not associated with abnormalities in the bleeding time. The simultaneous administration of heparin and aprotinin does not have a cumulative anti-coagulant effect although the presence of heparin with aprotinin results in prolonged prothrombin and bleeding times. Thus aprotinin does not reduce increased thrombosis in this model. We speculate that aprotinin may be the ideal agent for anti-coagulation in surgery.

Original languageEnglish
Pages (from-to)317-320
Number of pages4
JournalEuropean Journal of Vascular Surgery
Volume6
Issue number3
DOIs
Publication statusPublished - May 1992
Externally publishedYes

Keywords

  • Anti-coagulant
  • Aprotinin
  • Heparin
  • Thrombosis

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