Holding the Platelet Trigger

When platelets deliver their payload to the right address at the right time, they stop the bleeding and save the day. But abnormal platelet function, or an inappropriately timed trigger, can result in disaster. Platelets are a hot topic, not only in hematology, but in cardiology and vascular surgery, where antiplatelet drugs such as aspirin are a mainstay of therapy.

The recent report of a potential pro-thrombotic effect of rofecoxib (Vioxx) in coronary artery disease and stroke has raised concern about the platelet effects of the whole class of COX-2 inhibitors, particularly in the setting of pre-existing vascular disease. This has also turned the spotlight onto other drugs that could alter platelet function.

In today’s simultaneous session on Antithrombotic Therapy II at 3:30 p.m., Dr. Carol Sun will present data on the effect of NSAIDs and COX-2 inhibitors on aspirin function. In this study, healthy subjects were started on low-dose aspirin and received NSAIDs, COX-2 inhibitors, acetaminophen, or higher dose aspirin to determine if concomitant use of any of these medications affected platelet aggregation studies. Sun et al. conclude that COX-2 inhibitors and acetaminophen do not alter the effect of low-dose aspirin on platelets, and that NSAIDs in fact appear to accelerate the aspirin effect. The authors note that their findings are inconsistent with a previous report that ibuprofen interferes with aspirin’s effect on platelet aggregation, making Dr. Sun’s report a noteworthy addition to the growing body of evidence on the complex hemostatic effects of NSAIDs and the COX-2 inhibitor class. We suspect this, as well as other abstracts at this session related to antithrom-botic therapy, will spark an informative discussion.

Postmenopausal hormone therapy is another drug regimen with controversial thrombotic effects, particularly for coronary events. Today in Pathophysiology of Thrombosis: Clinical Studies at 1:30 p.m., Dr. Paul Bray will present data from the HERS study identifying differences in CHD event risk between placebo and hormone treatment groups depending on GPIb alpha and GPIV genotype. Interestingly, this includes some genotypes that were actually protective in the context of hormone therapy. These provocative reports should spur further study, though the jury is still out on how these observations will ultimately affect clinical decision making.

Multiple other sessions in today’s schedule offer ample opportunity to get up to speed on the latest in platelets, including Molecular Mechanisms of Platelet Function I and II, as well as a session on Acquired Thrombocytopenias. The Scientific Committee on Platelets session this weekend was also very useful. Dr. Hartwig gave an update on the molecular mechanisms of platelet production, followed by a discussion of the congenital thrombo-cytopenias by Dr. Drachman. Dr. Poncz’s talk on modified platelets as delivery agents served as the grand finale. He will also sponsor an abstract in tomorrow’s Animal Models in Coagulation session on the same topic.