The Effectiveness and Optimal Dosage of Low Molecular Weight Heparin in Cardiopulmonary Bypass Surgery in Pigs
DiMartino, Lisa Marie
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The interest in low molecular weight (LMW) heparin has increased with the demonstration of a higher antithrombotic potency of this heparin fraction than that of standard heparin. Experimentally, low molecular weight heparin has shown a discordance of anticoagulant effect and antithrombotic activity due to the reduced inhibition of thrombin by low molecular weight heparin. Furthermore, low molecular weight heparin differs from standard heparin in its in vivo half-life as well as its mode of action. Based on these data, a two phase experiment was designed to determine if low molecular weight heparin is a more efficient and safer antithrombotic drug with less side effects. Phase I revealed the Heptest assay to be the most effective test in determining the concentration of LMW heparin. The ability of protamine sulfate to neutralize heparin action was also demonstrated. During phase II, a porcine animal model of cardiopulmonary bypass surgery aided in the definition of an adequate dosage requirement to ensure the effectiveness of RD Heparin in preventing clotting in the extracorporeal circuit. It was demonstrated that low molecular weight heparin, at reduced dosages, is more effective in the prevention of clotting during bypass surgery than standard heparin at a higher dosage with equal anti Xa activity.