TY - JOUR
T1 - Viewpoint
T2 - Reversible nature of platelet binding causing transfusion-related acute lung injury (TRALI) syndrome may explain dyspnea after ticagrelor and elinogrel
AU - Serebruany, Victor L.
PY - 2012
Y1 - 2012
N2 - There may be a universal mechanism explaining dyspnea after ticagre-lor 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 elino-grel. The adenosine hypothesis has been offered to explain such adverse association. However, despite obvious similarity between ticagre-lor 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 Since both agents cause dyspnea, the adenosine hypothesis is no longer valid.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.
AB - There may be a universal mechanism explaining dyspnea after ticagre-lor 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 elino-grel. The adenosine hypothesis has been offered to explain such adverse association. However, despite obvious similarity between ticagre-lor 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.
KW - Adenosine
KW - Dyspnea
KW - Elinogrel
KW - Reversibility
KW - Ticagrelor
KW - TRALI
UR - http://www.scopus.com/inward/record.url?scp=84870901671&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870901671&partnerID=8YFLogxK
U2 - 10.1160/TH12-03-0180
DO - 10.1160/TH12-03-0180
M3 - Article
C2 - 23070029
AN - SCOPUS:84870901671
VL - 108
SP - 1024
EP - 1027
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 6
ER -