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Studies of the prothrombin activation pathway utilizing radioimmunoassays
for the F2/F1 + 2 fragment and thrombin--antithrombin complex
JM Teitel, KA Bauer, HK Lau and RD Rosenberg
We have evaluated the efficacy of utilizing radioimmunoassays (RIAs) for
prothrombin activation fragments (F2/F1 + 2) and for thrombin--
antithrombin complex (TAT) in purified systems and in whole blood. During
venipuncture, appropriate anticoagulants were employed in order to prevent
the generation of thrombin and factor Xa. The RIAs were shown to be
specific for F2/F1 + 2 as well as TAT and did not interact with other
plasma components. Initially, thrombin generation was studied in a purified
human system of prothrombin, antithrombin, factor Xa, and factor V as well
as phospholipid and Ca++. Under these conditions, the kinetics of F2/F1 + 2
and TAT generation were virtually superimposable. However, when factor V
was omitted from the reaction mixture, a significantly greater amount of
F2/F1 + 2 as compared to TAT was observable. Subsequently, prothrombin
activation was monitored during the spontaneous coagulation of freshly
drawn blood. Throughout the entire course of thrombin generation, the
observable rate of formation of F2/F1 + 2 was considerably greater than
that of TAT. We have examined the levels of F2/F1 + 2 and TAT in normal
individuals. Our studies indicate that the concentrations of F1 + 2 and TAT
average 1.97 nM and 2.32 nM, respectively. We have also quantitated the
concentrations of F2/F1 + 2 and TAT in patients with disseminated
intravascular coagulation. In these individuals, the levels of both
components are elevated. However, the ratio of F1 + 2 to TAT ranges from
2.37 to 5.55. Thus, we conclude that under in vivo conditions, prothrombin
activation is characterized by the accumulation of a stable precursor, such
as prethrombin-2, and that this phenomenon may be related to an alteration
of factor V function.
Volume 59,
Issue 5,
pp. 1086-1097,
05/01/1982
Copyright © 1982 by The American Society of Hematology
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