Platelet aggregometry readings spiked (to higher than baseline readings) in a canine study, after the onset of internal bleeding. Plavix was working and reduced aggregometry readings to desired levels, then swelling due to internal bleeding was observed. Was this a systemic response to allow coagulation to stop the bleeding?
Resistance to clopidogrel is already a documented process same is true for aspirin reference Catzung text book of basic and clinical pharmacology 13th edition 2015
What aggregation agonists were you using? It is likely that the platelets have responded to the bleeding situation - via collagen adhesion at the wound site? Drugs don't necessarily knock out all pathways for platelet activation
Thanks for the insight, Mr. Pattison. We used ADP as the agonist in the aggregometry readings. We used aspirin+plavix as our DAPT regimen. Very effective until the bleeding/swelling was observed - ~2 weeks post op. Our hypothesis is that there was a systemic response to activate the platelets to facilitate coagulation that stopped the bleeding. The vascular implants (source of bleeding) became occluded as a result. Ever hear of anything similar?
Obviously a combination of aspirin + plavix should give pretty good inhibition of platelet response. However, they do not shut off all responses - back in the 1980's I published work on some PDE III inhibitors, where we showed inhibition to Arachidonic Acid and ADP, but the collagen response was never fully inhibited and in fact was quite potent - I wonder if you are seeing something similar? Also, do you look at Arachidonic acid response if you are giving dual therapy?