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Heparin administration for operations with extracorporeal circulation (ECC) usually is performed following prefixed, standardized protocols. These regimens secure an adequate level of anticoagulation, hut they often involve prolonged periods of overheparinization associated with an undue risk of hemorrhage. The predictive value of preoperative studies on the anticoagulant effect of heparin was investigated in 10 patients. The study was performed both in vitro and in vivo using the Xa inhibitor assay as an index of the anticoagulation induced by heparin. Adding variable amounts of heparin in vitro to patient’s plasma resulted in straight (at least up to 7 U. per milliliter) and parallel, but not coincident, dose/response curves, so confirming a different individual sensitivity to heparin. Disappearance curves of the anticoagulant effect in plasma following intravenous administration of a single standard dose of heparin in the same patients showed an even greater patient-to-patient variability, with “half-life” times ranging from 30 to 150 minutes. No relationship was found between the two parameters (in vitro sensitivity to heparin and clearance rate from plasma in vivo). Moreover, neither of them could be correlated with the response to heparin, subsequently observed during ECC in the same patients. Preoperative investigations with the methods presently available are not adequate to choose individual heparin administration regimens for cardiac operations.