Summary
There may be a universal mechanism explaining dyspnea after ticagrelor and elinogrel,
namely, transfusion-related acute lung injury (TRALI). Indeed, recent clinical trials
with ticagrelor (DISPERSE, DISPERSE-II, and PLATO), and elinogrel (INNOVATE PCI) revealed
double-digit rates of dyspnea after novel reversible antiplatelet agents. In contrast,
dyspnea is not associated with conventional non-reversible agents such as aspirin,
or thienopyridines (ticlopidine, clopidogrel, or prasugrel) suggesting distinct mechanism
of shortness of breath after ticagrelor and elinogrel. The adenosine hypothesis has
been offered to explain such adverse association. However, despite obvious similarity
between ticagrelor and adenosine molecules, the chemical structure of elinogrel is
entirely different. In fact, ticagrelor is a cyclopentyl-triazolo-pyrimidine, while
elinogrel is a quinazolinedione. Since both agents cause dyspnea, the adenosine hypothesis
is no longer valid. In contrast, the reversible nature of platelet inhibition attributable
to both ticagrelor and elinogrel causing premature cell ageing, apoptosis, impaired
turnover due to sequestration of overloaded, exhausted platelets in the pulmonary
circulation are among potential autoimmune mechanism(s) resulting in the development
of a TRALI-like reaction, and frequent dyspnea. Despite expected benefit for better
bleeding control, further development of reversible antithrombins is severely limited
due to the existence of a potentially universal serious adverse event, such as TRALI-syndrome
with dyspnea as a predominant clinical manifestation. Since TRALI is an established
number one contributor to mortality after blood transfusions, ticagrelor death “benefit”in
PLATO is challenged further.
Keywords Ticagrelor - elinogrel - adenosine - TRALI - dyspnea - reversibility
