Summary
Recombinant platelet factor 4 (rPF4) efficiently neutralized heparin anticoagulant
activity in rats without the adverse effect of protamine sulfate (PS) (Circulation
1992; 85: 1102). This study confirmed that rPF4 and PS neutralized heparin in rats.
In vitro addition of excess PS but not rPF4 to plasma prolonged the activated partial
thromboplastin time. Injection of rPF4 or PS 2 min following injection of 3H-heparin augmented loss of radioactivity from the circulation over the first 2 min
but did not affect the half life of 3H-heparin for the next 58 min. PS was coupled to 4-(p-Azidosalicylamido)butylamine
(ASBA), radioiodina- ted and purified by means of heparin-agarose chromatography.
Heparin prevented the rapid loss of 125I-rPF4 from the circulation within the first 2 min but modestly increased loss of
radioiodinated derivatized PS. Heparin extended the half-life of derivitized radioiodinated
PS (measured between 2 and 60 min after injection) while modestly shortening that
of 125I-rPF4. Both radioiodinated heparin binding proteins accumulated predominantly in
liver and kidney. A greater percentage of radioactivity was found in these organs
with rPF4 than with PS but more PS was found in urine. A larger percentage of radioiodinated
derivatized PS than 125I-rPF4 was undetected. These results indicate that rPF4 and PS affect the kinetics
of heparin clearance similarly but that organ deposition of the two agents may differ
and offer an explanation of different physiological effects seen previously.
