Extracorporeal Elimination of Large Concentrations of Tirofiban by Zero-Balanced Ultrafiltration During Cardiopulmonary Bypass: An In Vitro Investigation

Abstract

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.

Pathophysiology of Bleeding and Clotting in the Cardiac Surgery Patient

“…For emergent cases and in the setting of intractable bleeding, increasing clearance of particular drugs with hemofiltration, hemodialysis, or plasmapheresis and increasing thrombin generation with recombinant activated factor VII or prothrombin complex concentrates should be considered for rescue therapy. 23 The individual features of antithrombotic agents are detailed in the Table. Intravenous unfractionated heparin therapy is familiar to most clinicians and is rapidly reversible with protamine sulfate. Low-molecular-weight heparin is much less likely to induce heparin-induced thrombocytopenia than unfractionated heparin and is dosed subcutaneously as a fixed dose by body weight, but its clearance is dependent on renal function, and it is only partially reversed by protamine.…”

Use of thromboelastography PlateletMapping™ to monitor antithrombotic therapy in a patient with Budd-Chiari syndrome

“…The patient was also started on an infusion of glycoprotein IIb/IIIa inhibition as additional antiplatelet therapy. Tirofiban was chosen because of its relatively short elimination half‐life of around 2 hours1 to allow the rapid offset of the antiplatelet effect if the patient developed bleeding. Repeat PFMT showed 100% platelet inhibition (Fig.…”

Case 1–2015

“…In the current case, the use of UFH and tirofiban would have been an option but only if extended MUF for augmenting extracorporeal elimination of tirofiban had been performed after CPB. 31 Nevertheless, a smaller risk of persisting hemorrhage due to incomplete extracorporeal elimination of tirofiban would have remained.…”