Chang LC, Liang JF, Lee HF, Lee LM and Yang VC Low Molecular Weight Protamine (LMWP)as Nontoxic Heparin/Low Molecular Weight Heparin Antidote (II): In Vitro Evaluation of Efficacy and Toxicity AAPS PharmSci 2001; 3 (3) article 18 (https://www.pharmsci.org/scientificjournals/pharmsci/journal/01_18.html).

Figures and Tables

Figure 1.Neutralization of heparin by protamine, TDSP5, TDSP4, or TDSP3, as measured by the aPTT clotting assay. The dotted line represents the baseline clotting time.

Figure 2.Neutralization of heparin by protamine, TDSP5, or TDSP4, as measured by anti-IIa chromogenic assay. The dotted line represents the control (ie, 100% neutralization).

Figure 3.Neutralization of LMWH5000-7000 (Mono-Embolex) by protamine, TDSP5, and TDSP4, as measured by anti-Xa chromogenic assay. The dotted line represents the control (ie, 100% neutralization).

Figure 4.Neutralization of LMWH3000 and Fragmin by TDSP5 as measured by anti-Xa chromogenic assay.

Figure 5.A, Effects of protamine and low molecular weight heparin (LMWP) alone on complement consumption. B, Effects of the heparin-protamine and heparin-LMWP complexes on complement consumption. Complexes were prepared by adding protamine (or LMWP) to serum samples containing an increasing concentration of heparin at the respective neutralization ratio (ie, for each unit of heparin, 10 µg or 22 µg of protamine and TDSP5, respectively, were added for the formation of heparin-[LMW]protamine complexes). For details, see the Material and Methods section.

Figure 6.Dose requirement for the inhibition of 50% of the enzyme-linked immunosorbent assay (ELISA) reaction by protamine, TDSP5, and TDSP4. The microplate wells were coated with protamine as the capturing agent. A competitive ELISA assay that involved the addition of protamine or the LMWP fractions (ie, TDSP4 and TDSP5) to mouse serum samples containing antiprotamine antibodies was performed. For a detailed description of this competitive ELISA assay, please see the Materials and Methods section.