Anesthesiology 1991 75:288–297.Ĭhang LC, Lee HF, Yang Z, Yang VC. The use of immobilized protamine in removing heparin and preventing protamine-induced complications during extracorporeal blood circulation. Yang VC, Port FK, Kim JS, Teng CL, Till GO, Wakefield TW. Acute pulmonary vasoconstriction and thromboxane release during protamine reversal of heparin anticoagulation in awake sheep: Evidence for the role of reactive oxygen metabolites following nonimmunological complement activation. Morel DR, Lowenstein E, Nguyenduy T, et al. Prospective evaluation of risk of protamine reactions in patients with NPH insulin-dependent diabetes. A prospective study of the risk of an immediate adverse reaction to protamine sulfate during cardiopulmonary bypass surgery. Weiler JM, Gellhaus MA, Carter JG, et al. Pharmacology & Physiology in Anesthetic Practice. A comparison of the strength of binding of antithrombin III, protamine and poly(1-lysine) to heparin samples of different anticoagulant activities. Furthermore, compared with protamine, TDSP5 exhibited a much-reduced toxicity and thus an improved safety profile, as reflected by its reduced ability to activate the complement system and cross-react with the antiprotamine antibodies, which are 2 primary indices of protamine toxicity. As assessed by the anti-Xa assay, TDSP5 was as effective as, although less potent than, protamine in reversing the activity of Mono-Embolex (molecular weight 5000–7000) and 2 other different sizes (molecular weight of 30 d) of LMWH preparations. Additionally, these LMWP fractions could neutralize the activities of commercial LMWH. These LMWP fractions, particularly TDSP5, were effective and fully capable of neutralizing a broad spectrum of heparin-induced anticoagulant activities (ie, aPTT, anti-Xa, and anti-IIa activities). In this, the second article in this series, studies focused on in vitro evaluation of heparin/LMWH-neutralizing efficacy and putative toxicity. We had previously developed 2 low molecular weight protamine (LMWP) fractions (TDSP4 and TDSP5) from thermolysin-digested protamine as potential nontoxie, heparin-neutralizing agents. Patients undergoing anticoagulation with heparin or low molecular weight heparin (LMWH) require a superior antidote that possesses more selective biological actions and a better safety profile than protamine.
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