Effects of aprotinin on plasma coagulation kinetics determined by thrombelastography: Role of Factor XI

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13 Scopus citations

Abstract

Background: Aprotinin is commonly administered in settings involving cardiopulmonary bypass and liver transplantation to decrease peri-operative bleeding. Thrombelastography has been utilized to monitor coagulation in these settings, and aprotinin delays clot initiation, presumably by inhibiting kallikrein; however, aprotinin also inhibits Factor XI (FXI), a contact system protein. Thus, it was hypothesized that celite-activated thrombelastography coagulation kin-etics would be decreased via aprotinin-mediated FXI inhibition. Methods: Citrated normal plasma and prekallikrein-deficient (<1% normal activity) plasma were exposed to 0, 200, 400 or 800 kallikrein inhibitory units (KIU)/ml (n = 6 per condition). Samples were recalcified and celite-activated in a thrombelastograph, with clot initiation (R, s) determined. To confirm contact system specificity, additional prekallikrein-deficient samples with 0 or 800 KIU/ml aprotinin were activated with tissue factor (n = 4 per condition). Results: Exposure of celite-activated, normal plasma to aprotinin 0, 200, 400 or 800 KIU/ml resulted in R values of 167 ± 14, 253 ± 10, 293 ± 22 and 349 ± 21 s, respectively, which were significantly different from one another (P < 0.05). Exposure of celite-activated, prekallikrein-deficient plasma to aprotinin 0, 200, 400 or 800 KIU/ml resulted in R values of 366 ± 15, 630 ± 64, 698 ± 46 and 850 ± 47 s, respectively, which were significantly different from one another (P < 0.05). There were no significant differences in R values between tissue factor-activated, prekallikrein-deficient plasma samples with 0 or 800 KIU/ml aprotinin. Conclusions: These data support a role for the inhibition of FXI as the mechanism for aprotinin-mediated delayed contact system clot initiation determined by thrombelastography.

Original languageEnglish (US)
Pages (from-to)168-172
Number of pages5
JournalActa Anaesthesiologica Scandinavica
Volume50
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Keywords

  • Aprotinin
  • Factor XI
  • Kallikrein
  • Kininogen
  • Thrombelastography

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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