Neutralization of the antithrombotic effects of heparin and Fraxiparin by protamine sulfate. 1992

A Racanelli, and J Fareed
Loyola University Medical Center, Maywood, IL 60153.

In general, the in vitro anti Xa activity of low molecular weight heparins is neutralized to a lesser degree than the anti Xa activity of unfractionated heparin. To determine whether these differences occur in vivo, a rabbit stasis thrombosis model and a rat laser-induced thrombosis model were utilized. In the laser model, a similar degree of neutralization of the antithrombotic activity of heparin and Fraxiparin was obtained. However, in the stasis thrombosis model, significant antithrombotic activity of Fraxiparin remained after equigravimetric protamine administration. Ex vivo APTT, thrombin time, Heptest, amidolytic anti Xa and anti IIa assays were performed. A coefficient (r = .806) was obtained for the correlation of Heptest activity to antithrombotic effect in the stasis thrombosis model, while the coefficients obtained for the other tests ranged from .152-.570. However, after neutralization by protamine, the thrombin time exhibited the highest correlation coefficient (r = .685) between ex vivo activity and residual antithrombotic effect. Since Fraxiparin retains antithrombotic activity after protamine administration, clinical benefit may be observed for this low molecular weight heparin as compared to unfractionated heparin after neutralization.

UI MeSH Term Description Entries
D007834 Lasers An optical source that emits photons in a coherent beam. Light Amplification by Stimulated Emission of Radiation (LASER) is brought about using devices that transform light of varying frequencies into a single intense, nearly nondivergent beam of monochromatic radiation. Lasers operate in the infrared, visible, ultraviolet, or X-ray regions of the spectrum. Masers,Continuous Wave Lasers,Pulsed Lasers,Q-Switched Lasers,Continuous Wave Laser,Laser,Laser, Continuous Wave,Laser, Pulsed,Laser, Q-Switched,Lasers, Continuous Wave,Lasers, Pulsed,Lasers, Q-Switched,Maser,Pulsed Laser,Q Switched Lasers,Q-Switched Laser
D008297 Male Males
D011479 Protamines A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692) Protamine,Protamine Sulfate,Protamine Chloride,Chloride, Protamine,Sulfate, Protamine
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001780 Blood Coagulation Tests Laboratory tests for evaluating the individual's clotting mechanism. Coagulation Tests, Blood,Tests, Blood Coagulation,Blood Coagulation Test,Coagulation Test, Blood,Test, Blood Coagulation
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006487 Hemostasis The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION. Hemostases
D006494 Heparin Antagonists Coagulant substances inhibiting the anticoagulant action of heparin. Antagonists, Heparin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013927 Thrombosis Formation and development of a thrombus or blood clot in BLOOD VESSELS. Atherothrombosis,Thrombus,Blood Clot,Blood Clots,Thromboses

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