Effects of aprotinin on plasma coagulation kinetics determined by thrombelastography: role of Factor XI.
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.
Nielsen
V G
VG
Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35249-6810, USA. vnielsen@uab.edu
D007611:Aprotinin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005172:Factor XI / Q000187:drug effects* / Q000502:physiology; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007700:Kinetics; D013916:Thrombelastography / Q000187:drug effects* / Q000379:methods
D006490:Hemostatics; D005172:Factor XI; D007611:Aprotinin; D007610:Kallikreins