Circulation, Vol 85, 1102-1109, Copyright © 1992 by American Heart Association
JJ Cook, S Niewiarowski, Z Yan, L Schaffer, W Lu, GJ Stewart, DM Mosser, JA Myers and TE Maione
BACKGROUND. It has been observed that the reversal of heparin
anticoagulation in humans by protamine sulfate (PS) results in various
adverse reactions including leukopenia, thrombocytopenia, activation of
complement, increased vascular permeability, systemic hypotension,
pulmonary vasoconstriction, and pulmonary edema. The purpose of this study
was to compare the efficacy and effects of native platelet factor 4 (PF4)
and recombinant platelet factor 4 (rPF4) with those of PS in heparin
neutralization in vivo, using a rat model. METHODS AND RESULTS.
Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the
right femoral vein and carotid artery were cannulated. For determination of
activated partial thromboplastin time, platelet count, white blood cell
count, and complement titer, arterial blood samples were taken before and
immediately after heparin (10 units/100 g) infusion and at several time
points after the infusion of the neutralizing agent (PS, 0.1 mg/100 g; PF4,
0.5 mg/100 g). In separate groups of animals, mean arterial blood pressure
was monitored throughout identical protocols and the lungs were prepared
for histological examination. The anticoagulant activity of heparin was
effectively reversed by all of the neutralizing agents (PS, PF4, and rPF4).
Platelet count (48% of initial), white blood cell count (52% of initial),
complement titer (60% of initial), and mean arterial pressure (20%
decrease) decreased significantly in heparinized animals receiving PS but
not in those receiving PF4 or rPF4. Lung interstitium appeared normal when
heparin was followed by PF4; however, interstitial edema and hemorrhage
were observed with heparin-PS. CONCLUSIONS. These results suggest that PF4
efficiently reverses heparin anticoagulation in the rat without the adverse
effects of heparin-protamine complexes. Therefore, rPF4 may be an
appropriate substitute for PS in patients undergoing cardiovascular surgery
and other procedures that require heparin anticoagulation.
ARTICLES
Platelet factor 4 efficiently reverses heparin anticoagulation in the rat without adverse effects of heparin-protamine complexes
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140.
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