title: Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors?
abstract: Platelet inhibitors, especially the glycoprotein (GP) IIb/IIIa receptor antagonists, have demonstrated their effectiveness in reducing the acute ischemic complications of percutaneous coronary intervention (PCI) and in improving clinical outcomes in patients with acute coronary crisis. Three common platelet inhibitors observed in emergent cardiopulmonary bypass (CPB) for failed PCI are abciximab, eptifibatide, and tirofiban. An in vitro model was constructed in two parts to determine whether platelet aggregation inhibition induced by platelet inhibitors would be demonstrated by the Thrombelastograph (TEG) monitor when compared with baseline samples with no platelet inhibitor. In part A, 20 mL of fresh whole blood was divided into four groups: group I = baseline, group A = abcix-imab microg/mL, group E = eptifibatide ng/mL, and group T = tirofiban ng/mL. Platelet inhibitor concentrations in whole blood were derived starting with reported serum concentrations with escalation to achieve 80% platelet inhibition using the Medtronic hemoSTATUS and/or Lumi-aggregometer. A concentration range determined by our in vitro tests were chosen for each drug using concentrations achieving less than, equal to, or greater than 80% platelet inhibition. In part B, TEG analysis was then performed using baseline and concentrations for each drug derived in part A. Parameters measured were clot formation reaction time (R), coagulation time (K), maximum amplitude (MA) and alpha angle (A). Groups E1000 and E2000 extended R over control by 37% and 23%, respectively (p = 0.01 and 0.03). Groups E1000 and E2000 increased K times by 45% and 58% (p = .02 and .04). T160 samples prolonged K by 20% (p = 0.01). The angle or clot strength (A) was decreased in groups T160 and E1000 by 23% (+ 7.06 SD) and 18% (+ 11.23 SD), respectively (p = 0.001 and 0.01). The MA decrease was statistically significant in the T160, E1000 and E2000 by 9%, 6% and 13% respectively (p = 0.01). Samples treated with abciximab were comparable to control values for all parameters measured. Although statistical significance could be demonstrated with some parameters, sensitivity was only observed at increased doses and was not seen with all agents tested. In our in vitro model, the TEG monitor was unable to demonstrate clinically significant differences in platelet function and may not be reflective of platelet function in samples which have been treated with these GP IIb/IIIa inhibitors.
authors.affiliation: Department of Cardiovascular Perfusion, Medical University of South Carolina, Charleston, South Carolina, USA. labailey@hotmail.com
authors.forename: Lori A
authors.initials: LA
authors.lastname: Bailey
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Sistino
authors.forename: Walter E
authors.initials: WE
authors.lastname: Uber
mesh_terms: D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000379:methods; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology*; D001792:Blood Platelets; D000077542:Eptifibatide; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000494:pharmacology*; D066298:In Vitro Techniques; D039661:Integrin beta3 / Q000187:drug effects; D008962:Models, Theoretical; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000295:instrumentation*; D040201:Platelet Membrane Glycoprotein IIb / Q000187:drug effects; D019095:Point-of-Care Systems; D013916:Thrombelastography / Q000295:instrumentation* / Q000592:standards; D000077466:Tirofiban; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab