Viewpoint: Reversible nature of platelet binding causing transfusion-related acute lung injury (TRALI) syndrome may explain dyspnea after ticagrelor and elinogrel

Victor L. Serebruany

Research output: Contribution to journalArticlepeer-review

Abstract

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 Since both agents cause dyspnea, the adenosine hypothesis is no longer valid.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.

Original languageEnglish (US)
Pages (from-to)1024-1027
Number of pages4
JournalThrombosis and Haemostasis
Volume108
Issue number6
DOIs
StatePublished - 2012

Keywords

  • Adenosine
  • Dyspnea
  • Elinogrel
  • Reversibility
  • Ticagrelor
  • TRALI

ASJC Scopus subject areas

  • Hematology

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