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Heparin and antithrombin III (AT III) levels were followed in ten patients during cardiopulmonary bypass surgery in a pilot study designed to assess the adequacy of the local conventional protocol for heparinization and reversal. Heparin was administered according to the local standard procedure on the basis of body surface area and was neutralized by doses of protamine sulphate calculated on the basis of the initial loading dose of heparin. A fluorometric method was employed to assay plasma heparin and AT III concentrations using the synthetic fluorescent tripeptide, H-D-phe-pror-arg-5-amidoisophthalic acid, dimethyl ester, as the thrombin substrate. Heparin levels were in the range of 2.0 to 6.5 IU/ml during bypass with significant differences between and within patients in response to periodic additional injections of heparin, due to neutralization of heparin by PF4 released during bypass. All patients showed a sudden drop in the level of AT III of 15 - 35 IU/dl after the initial dose of heparin given before the start of surgery. The AT III levels varied greatly during bypass both between and within patients, falling to as low as 11 IU/dl in one patient whose pre-heparin level was below the normal range, and to zero in another patient. AT III levels rose after administration of whole blood or frwh frozen plasma, and most patients recovered to within 30 IU/dl of original AT III concentration. In all cases the amount of protamine sulphate administered to neutralize heparin was excessive. The diversity of observed patient responses to heparin, heparin neutralization by PF4 release, half-life of heparin, and AT III levels demonstrates the requirement for monitoring heparin and AT III levels before, during and after cardiopulmonary bypass surgery to maintain heparin concentration within a specified range, to facilitate the exact neutralization of heparin at the conclusion of bypass and to assure adequate levels of endogenous AT III prior to surgery and to maintain sufficient concentration of AT III during bypass to ensure the desired anticoagulant effect.

Heparin And Antithrombin III.Levels During Cardiopulmonary Bypass Surgery-A Pilot Study