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Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue
thromboplastin-induced intravascular coagulation in the rabbit
KC Day, LC Hoffman, MO Palmier, KK Kretzmer, MD Huang, EY Pyla, E Spokas, GJ Broze , TG Warren and TC Wun
Monsanto Corporate Research, Chesterfield, MO 63198.
Lipoprotein-associated coagulation inhibitor produces feed-back inhibition
of tissue factor (tissue thromboplastin)-induced coagulation in the
presence of factor Xa Recombinant lipoprotein-associated coagulation
inhibitor (rLACI) was tested for its ability to modify
thromboplastin-induced intravascular coagulation in a rabbit model that
allows monitoring of iodine-125 fibrin accumulation/disappearance in the
lung and sampling of blood for the measurement of coagulation parameters.
Infusion of thromboplastin into the rabbit caused a rapid increase of
radioactivity over the lungs, possibly due to the accumulation of 125I
fibrin in the lungs, followed by a rapid decline of radioactivity,
suggestive of removal of fibrin from the lungs. Thromboplastin also caused
a rapid decrease of systemic fibrinogen that was accompanied by a
lengthening of the activated partial thromboplastin time and prothrombin
time. The effect of coinfusion of rLACI with thromboplastin or bolus
injection of rLACI before thromboplastin infusion was studied. At a high
dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced
radioactivity increase in the lungs and the systemic fibrinogen decrease
were completely suppressed. The activated partial thromboplastin time and
prothrombin time of the plasma samples lengthened, possibly due to the
presence of thromboplastin in circulation. The thromboplastin-induced
radioactivity increase over the lungs was not completely suppressed by
lower doses of rLACI (135 to 270 micrograms/kg body weight), but these
doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of
23 micrograms/kg body weight, rLACI provided 50% protection of the
fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in
rabbits treated with thromboplastin alone). These results show that rLACI
is effective in the inhibition of thromboplastin-induced coagulation in
vivo.
Volume 76,
Issue 8,
pp. 1538-1545,
10/15/1990
Copyright © 1990 by The American Society of Hematology
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