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DEGR-factor Xa blocks disseminated intravascular coagulation initiated by
Escherichia coli without preventing shock or organ damage
FB Taylor , AC Chang, GT Peer, T Mather, K Blick, R Catlett, MS Lockhart and CT Esmon
Cardiovascular Biology Research, Oklahoma Medical Research Foundation,
Oklahoma City 73104.
One of the aims of research in the area of thrombosis has been to design an
effective anticoagulant that would function in a predictable and direct
manner. In evaluating the role of coagulation in sepsis we used factor Xa
blocked in the active center with [5-(dimethylamino)1-
naphthalenesulfonyl]-glutamylglycylarginyl+ ++ chloromethyl ketone
(DEGR-Xa). We infused 1 mg/kg of DEGR-Xa together with LD100 concentrations
of Escherichia coli (4 x 10(10) organisms/kg) into five baboons. As
controls, we infused E coli alone into five baboons. The inflammatory,
coagulant, and cell injury responses to E coli of both the treated and
control groups were lethal and were similar in every respect except for the
complete inhibition of the consumption of fibrinogen in the DEGR-Xa group.
The half life of DEGR-Xa was approximately 10 hours and 2 hours, as
determined by isotopic and enzyme-linked immunosorbent assays,
respectively. These results for the first time demonstrate that, although
coagulation occurs in E coli sepsis, fibrin formation per se did not
influence the lethal outcome in this model. These results also show the
effectiveness of DEGR-Xa as an anticoagulant and raise the possibility that
it could serve as an alternative to anticoagulants currently in use.
Volume 78,
Issue 2,
pp. 364-368,
07/15/1991
Copyright © 1991 by The American Society of Hematology
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