Previous in vitro studies using spontaneously clotting whole blood revealed
thrombin formation and high
fibrinopeptide A (FPA) concentrations measured during incubation time. This occurred in spite of normal concentrations of
thrombin antagonists present in the blood of the healthy subjects examined. However, there are several reports showing that in vivo increased
thrombin-antithrombin III-complex (TAT) concentrations and relatively low FPA concentrations may occur e.g. in patients with (pre)thrombotic disorders. These in vivo findings indicate more effective
thrombin inhibition by
antithrombin III, with almost no
fibrin formation. To find an explanation for the differences observed in vitro and in vivo, we extended the in vitro studies by measuring concentrations of
prothrombin fragment 1 + 2 (F1 + 2), TAT and FPA at several time points until 30 min. Our goal was to test whether
thrombin at least initially is neutralized by
antithrombin III, resulting in a lack of
fibrin formation, either in the absence or in the presence of
heparin (0.2 and 0.5 U/ml whole blood, respectively). In the absence of
heparin a simultaneous increase in the concentrations of F1 + 2, TAT and FPA was observed.
Thrombin was only partially neutralized by
antithrombin III and large amounts of
fibrin were formed. The addition of
heparin virtually suppressed
thrombin formation since the F1 + 2 concentration remained low. Moreover, the small amounts of
thrombin formed were neutralized by
antithrombin III to a greater extent than in the absence of
heparin.(ABSTRACT TRUNCATED AT 250 WORDS)