Extracorporeal elimination of large concentrations of tirofiban by zero-balanced ultrafiltration during cardiopulmonary bypass: an in vitro investigation.

The short-acting platelet glycoprotein IIb/IIIa antagonist tirofiban is beneficial when used in the context of cardiac surgery. Tirofiban has an elimination half-life of 2 h. Renal failure prolongs the half-life and continues inhibition of platelet aggregation refractory to transfusions of platelets. Extracorporeal elimination is necessary to prevent excessive hemorrhage in this condition. We assessed the elimination of tirofiban by hemofiltration in an in vitro model of cardiopulmonary bypass (CPB). Two hemofilters and one plasmapheresis filter were assessed. Three separate filters of each type were tested serially. The CPB circuit was primed with a total volume of 1000 mL. Tirofiban was added to a calculated concentration of 200 ng/mL. Portions of 50 mL of filtrate were retrieved from the dialyzer, and equal amounts of fluid were substituted in the circuit. After each filtration, the tirofiban blood level was analyzed. The procedure was repeated 16 times. Peak tirofiban concentrations ranged from 160 to 260 ng/mL. The elimination of tirofiban followed an exponential decay curve with fast clearance of the large therapeutic concentrations of 250 to 50 ng/mL. The subsidence coefficient b revealed no significant differences in elimination between the filter systems. These data suggest that ultrafiltration is an effective means for extracorporeal elimination of therapeutic levels of tirofiban.

Management of heparin resistance during cardiopulmonary bypass: the effect of five different anticoagulation strategies on hemostatic activation.

OBJECTIVE: Attenuation of hemostatic activation is a central goal during CPB. However, this poses a problem in patients insensitive to heparin. The present investigation was performed to assess different strategies of managing patients with heparin resistance during CPB. DESIGN: A randomized, prospective clinical investigation. SETTING: A major European heart center. PARTICIPANTS: Five groups with 20 patients each were investigated. INTERVENTIONS: The groups were handled as follows: (1). maintenance of a target ACT, (2). maintenance of the target unfractionated heparin (UFH) level and supplementation of a UFH level-based strategy with (3). AT III, (4). the direct thrombin inhibitor r-hirudin, or (5). the short-acting platelet glycoprotein (GP) IIb/IIIa antagonist tirofiban. Platelet count and generation of contact factor XIIa, thrombin, and soluble fibrin were assessed. Samples were obtained before CPB and after CPB before protamine infusion. MEASUREMENTS AND MAIN RESULTS: There were no differences observed in the generation of factor XIIa. The UFH-based strategy and supplementation with AT III, r-hirudin, and tirofiban resulted in significantly reduced (p < 0.05) thrombin generation compared with ACT management. A significant reduction of fibrin formation was seen only in patients who received AT III, r-hirudin, or tirofiban supplementation to the UFH. The administration of tirofiban resulted in a significant preservation of the platelet count compared with the other groups. There were no significant differences in the postoperative blood loss. CONCLUSIONS: Activation of hemostasis during CPB in heparin-resistant patients most likely has to be attributed to stimulation of the tissue factor pathway. Even the sole use of high concentrations of UFH does not effectively inhibit this activation. Therefore, in these patients anticoagulation during CPB with UFH should be supplemented with either AT III, a short-acting direct thrombin inhibitor, or a short-acting platelet glycoprotein IIb/IIIa antagonist.

The plasma supplemented modified activated clotting time for monitoring of heparinization during cardiopulmonary bypass: a pilot investigation.

UNLABELLED: The standard celite or kaolin activated clotting time (ACT) correlates poorly with heparin levels during cardiopulmonary bypass (CPB). We compared a modified kaolin ACT, in which plasma was supplemented, to a standard undiluted kaolin ACT for monitoring heparin levels during CPB. Fifteen patients undergoing normothermic CPB were enrolled in this prospective study. Heparin management was performed according to the Hepcon HMS results (Medtronic, Minneapolis, MN). The ACTs were performed with the ACT II device (Medtronic). Hepcon HMS calculations, standard kaolin ACTs, and plasma supplemented modified ACTs (mACTs), prepared by diluting blood samples 1:1 with human plasma (Behring, Marburg, Germany), were measured every 30 min during CPB. The data obtained were correlated to the plasma chromogenic anti-Xa activity as a reference assay for heparin levels. A total of 64 samples were evaluated. The chromogenic anti-Xa activity ranged from 0.2 to 5.5 IU/mL. The Hepcon HMS calculations ranged from 2.7-8.2 IU/mL of heparin, the standard ACT ranged from 424 to >999 s, and the mACT ranged from 210 to 801 s. The correlation to the chromogenic anti-Xa method was r = 0.43 for the standard kaolin ACT and r = 0.69 for the plasma mACT. The plasma mACT provided an improved correlation to chromogenically measured levels of anti-Xa activity during CPB. The improved correlation most likely results from a correction of the effects of the impairment of the coagulation system caused by hemodilution and consumption of procoagulants on extracorporeal surfaces. IMPLICATIONS: During cardiopulmonary bypass, the plasma modified kaolin activated clotting time (ACT) provides a better correlation with heparin levels than the standard kaolin ACT.