Here’s a new message from Kim Kinney at Clarian in Indianapolis:
Hi George, I have a question in regards to platelet aggregation and the effects of plavix and aspirin. We have had several patients where just the AA, ADP and collagen are abnormal but we have had a few where the ristocetin is also abnormal! Do you know what the mechanism could be? Thanks, we are awaiting our CAP inspection and everyone is on alert!
Kim
Hi, Kim. I hope your inspection goes well. From what I have seen of your lab, you have little to worry about.
I’m in Myrtle Beach SC preparing to do a talk at the Carolinas Clinical Connection on monitoring aspirin, so I will try to work your question into my presentation tomorrow morning. To tell you the truth, I had no answer so I called Dr. Larry Brace at Edwards Hospital in Chicago. He says that while ristocetin triggers platelet agglutination, the platelets still have to aggregate to give a full response. So if the VWF level is at all reduced, the aggregation does not occur when there is aspirin present. If the VWF is normal, the reaction is strong enough to drive the platelets to full aggregation. This seems logical, but there is no publication I know of supporting this. I’d like to get some backup, and maybe Emanual Favaloro, PhD will see this and add his own slant, since he has studied aspirin resistance testing and VWF activity levels. Geo.
Someone told me that my opinion was sought on this topic. I
Someone told me that my opinion was sought on this topic. I do not consider myself an expert on aspirin resistance despite Georges (misplaced) belief, although I do have a strong viewpoint that most of the aspirin resistance ‘identified’ by the PFA-100 is not really related to ‘aspirin non-responsiveness’ as such, but rather to other things like high plasma VWF levels – given that the PFA-100 is a global test of ‘plt function’ (see Kilanowska et al, Blood Coag Fibrinolysis, 2008; 19:823-824). In respect to the question at hand, aspirin works by irreversibly acetylating the cyclooxygenase (COX-1) enzyme, thus suppressing the production of thromboxane A2 (TxA2) and inhibiting platelet activation and aggregation. Interestingly, the so called ‘secondary phase’ of aggregation sometimes observed following a test challenge with ristocetin is thought to be due to a secondary event of TxA2 production resulting from plt-plt contact and agglutination initiated by risto (see Cattaneo, Semin Thromb Hemost, 2009;35:158167). So, in theory, this secondary phase would be inhibited by aspirin, and thus it would be entirely feasible to obtain a lower overall max agg response given the right test conditions. But, this is not something I have ever formally investigated.