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  • Title: Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man.
    Author: Wolzt M, Weltermann A, Nieszpaur-Los M, Schneider B, Fassolt A, Lechner K, Eichler HG, Kyrle PA.
    Journal: Thromb Haemost; 1995 Mar; 73(3):439-43. PubMed ID: 7667826.
    Abstract:
    In a double-blind, randomized, cross-over study the neutralizing action of protamine towards unfractionated heparin (UFH, 150 U/kg i.v.) and a low molecular weight heparin (LMWH, Fragmin, 100 anti-Xa U/kg i.v.) was investigated in 15 healthy subjects in vitro by measuring activated partial thromboplastin time (APTT), thrombin time (TT) and anti factor Xa activity (anti-Xa) in venous blood and in vivo by determination of prothrombin fragment 1.2 (f1.2) and thrombin-antithrombin III complexes (TAT) in venous blood and in shed blood. UFH and LMWH caused a prolongation of APTT and TT, an increase in anti-Xa and significantly inhibited f1.2 and TAT formation in shed blood, whereas only a minimal effect on TAT and f1.2 formation in venous blood was noted. Administration of 1 mg protamine/100 U UFH resulted in a near complete reversal of APTT, TT and anti-Xa, whereas lower doses (0.25 and 0.5 mg) were less effective. The effects of UFH on f1.2 and TAT generation in shed blood were partially (60-70%) neutralized only by the high dose (1.0 mg). Application of 1 mg protamine/100 anti-Xa U LMWH caused a near complete reversal of both APTT and TT but had only a weak effect on anti-Xa. In shed blood, the effect of LMWH on TAT and f1.2 formation was reversed by protamine only by 14% and 23% respectively. Our data do not support the concept that to reduce the incidence of protamine's potential clinical side effects, the administration of a lower dose of protamine than 1 mg protamine/100 U UFH is justified.(ABSTRACT TRUNCATED AT 250 WORDS)
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