Viewpoint: reversible nature of platelet binding causing transfusion-related acute lung injury (TRALI) syndrome may explain dyspnea after ticagrelor and elinogrel.
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 Since both agents cause dyspnea, the adenosine hypothesis is no longer valid.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.
HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA. heartdrug@aol.com
Victor L
VL
Serebruany
D055371:Acute Lung Injury / Q000097:blood* / Q000209:etiology* / Q000276:immunology; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D004417:Dyspnea / Q000097:blood / Q000209:etiology; D006801:Humans; D008954:Models, Biological; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D052999:Quinazolinones / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects*; D013577:Syndrome; D000077486:Ticagrelor; D065227:Transfusion Reaction
D010975:Platelet Aggregation Inhibitors; D052999:Quinazolinones; D013449:Sulfonamides; C549473:elinogrel; D000077486:Ticagrelor; D000241:Adenosine