Does Preoperative Level of Antithrombin III Predict Heparin Resistance During Extracorporeal Circulation?

To the Editor: Heparin resistance is characterized by an inadequate response to the large dose of heparin required for the safe initiation or maintenance of cardiopulmonary by-pass (CPB) and may be defined as the failure to achieve the desired activated clotting time (ACT) following a standard dose of heparin (300–400 U/kg). Failure to achieve an acceptable ACT for CPB is usually managed by administration of additional heparin and less frequently, by administration of fresh frozen plasma (FFP) in a attempt to restore heparin responsiveness.1,2 Heparin resistance is attributed to subnormal plasma antithrombin III (AT III) activity.2 We assessed whether the preoperative value of plasma AT III affects the dose of heparin required to achieve adequate anticoagulation as determined by an ACT equal to or greater than 480 s before CPB. After approval by our Ethics Committee 44 patients undergoing different cardiac surgery procedures requiring CPB were studied. All participants gave their written consent to participate in the study. Twenty-six patients underwent coronary revascularization, 13 underwent valvular repair and/or replacement, and five underwent mixed procedures. Before the start of CPB, AT III plasma activity and ACT were determined, after which 300 U/kg of heparin was administered IV. If the ACT obtained was <480 s, 100 U/kg of heparin was added IV and if the ACT obtained was again <480 s 500 U of AT III concentrate was administered followed by additional AT III as needed based on the ACT; initiating CPB after adequate anticoagulation had been established. Demographic data, preoperative medication, the antifibrinolytic agent employed and plasma urea, creatinine and prothrombin activity values were recorded before surgery. Twenty-six patients had low plasma AT III activity before CPB (AT III activity <80%; the mean AT III activity was 69%). Of these, 16 patients required administration of AT III concentrate (six received 500 U, two received 750 U, and eight received 1000 U) for adequate anticoagulation. There was no difference with respect to the other data. AT III supplementation has been used to improve the ACT response to heparin in patients with heparin resistance.1 Levy et al.3 established that a single dose of 75 U/kg or more of recombinant human AT III resulted in plasma AT III levels approximating 100% activity that were maintained during CPB. We agree with Levy et al.4 that the optimal dose of AT III to improve heparin response is not known but 1000 U may increase the ACT to an acceptable level. Patients with heparin resistance are often given FFP as a source of AT III but preparation of plasma requires time for ordering, thawing, delivery to the operating room and is not an innocuous intervention because it carries the risk of complications including viral infections and allergic reactions.2,5 It is possible that FFP increases AT III concentrations when large volumes (>2 L) are administered.1 Four units of FFP (approximately 250 mL/U, 1 U of AT III/mL) would cost approximately $185.00 and 1000 U of AT III concentrate $540.00. In summary, we consider preoperative plasma AT III activity as a predictive indicator that together with ACT values <480 s after heparin, indicate heparin resistance and the need to administer AT III concentrate to achieve correct anticoagulation during CPB. In accordance with Levy et al.,4 the dose that we recommend of AT III concentrate in cases of heparin resistance is 1000 U. José M. Rodríguez-López, MD Department of Anesthesiology University Hospital of Salamanca Salamanca, Spain [email protected] Esther del Barrio, MD Department of Anesthesiology University Hospital of Salamanca Salamanca, Spain Francisco S. Lozano, MD Department of surgery University Hospital of Salamanca Salamanca, Spain Clemente Muriel, MD Department of Anesthesiology University Hospital of Salamanca Salamanca, Spain