The effect of milrinone on platelet activation as determined by TEG platelet mapping.
BACKGROUND
Milrinone is a phosphodiesterase III inhibitor that increases intracellular cyclic adenosine monophosphate resulting in improved ventricular function and vasodilation. Increased intracellular levels of cyclic adenosine monophosphate also inhibit adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation. We hypothesized that inhibition of ADP and AA-induced platelet activation by therapeutic blood concentrations of milrinone could be quantified using TEG Platelet Mapping.


METHODS
Blood was taken from 15 healthy adults who had not been taking antiplatelet medications. Milrinone was added to whole blood in three clinically relevant concentrations (30, 100, and 300 ng/mL). Conventional thromboelastography (TEG) and TEG Platelet Mapping were performed on whole blood without milrinone and at each of these three concentrations.


RESULTS
Increased blood concentrations of milrinone were associated with increased inhibition of ADP and AA-induced platelet activation (P < 0.0001). Milrinone at a blood concentration of 300 ng/mL markedly impaired the platelet activation response to ADP and AA.


CONCLUSIONS
Therapeutic blood concentrations of milrinone exhibit a significant inhibitory effect on ADP and AA-induced platelet activation as determined by TEG Platelet Mapping, without affecting the conventional kaolin-activated TEG. We suggest that TEG Platelet Mapping results be interpreted with caution in patients being treated with milrinone, and other drugs that modify platelet cyclic nucleotide concentrations.
Department of Anesthesia, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Mark C
MC
Wesley
Francis X
FX
McGowan
Robert A
RA
Castro
Sheahan
S
Dissanayake
David
D
Zurakowski
James A
JA
Dinardo
D000244:Adenosine Diphosphate; D000328:Adult; D016718:Arachidonic Acid; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013916:Thrombelastography
D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D020105:Milrinone