title: Effect of rapid desensitization on platelet inhibition and basophil activation in patients with aspirin hypersensitivity and coronary disease.
abstract: To determine antiplatelet efficacy after desensitization in patients with a history of aspirin hypersensitivity.
  
  
  
  We conducted a case-control study to evaluate the efficacy of aspirin 1 day (D1) and 6-8 weeks (W6-8) after desensitization. We also assessed ex vivo basophil reactivity to aspirin after desensitization. Cases were patients with coronary artery disease (CAD) and documented history of aspirin hypersensitivity who underwent rapid successful oral desensitization to aspirin. Controls were patients with stable CAD without hypersensitivity and receiving aspirin. Among 56 cases, 27 received aspirin for acute coronary syndromes and 29 were treated for stable CAD. Aspirin was effective (defined as light transmission aggregometry induced by arachidonic acid ≤20%) at D1 in 86% of cases (P = 0.045 vs. controls) and in 95% at W6-8, vs. 100% of controls (P = 0.39). Urinary excretion of thromboxane B2 diminished substantially in cases (P < 0.0001, D0 vs. W6-8) but remained higher than in controls (P = 0.03). Platelet reactivity (defined by platelet P-selectin expression, activated glycoprotein IIb/IIIa inhibitors, and platelet-monocyte aggregates) was similar in cases between D0 and D1 but decreased at W6-8. Basophil activation (quantified by upregulation of CD203c in response to aspirin) was higher in cases at W6-8 than in controls (P = 0.0002).
  
  
  
  Thus, following rapid desensitization, aspirin achieves rapid biological efficacy, which is slightly lower at D1, but becomes indistinguishable from chronically treated patients at W6-8. Persistent basophil activation several weeks after desensitization suggests infraclinical hypersensitivity and the need to continue aspirin to maintain desensitization.
authors.affiliation: Département de Cardiologie, Hopital Lariboisière, Paris, France.|INSERM UMR-S 942, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|Département Hospitalo-Universitaire FIRE Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Manzo-Silberman
authors.affiliation: Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Bichat, Unité d'Immunologie, Auto-immunité et Hypersensibilités, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Nicaise-Roland
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Service de Pneumologie Allergologie, Hôpitaux Universitaires Paris Nord Val de Seine, AP-HP Hôpital Bichat, Paris, France.|INSERM UMR 1152, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Neukirch
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Département d'épidémiologie et recherche clinique, CIC-EC 1425, AP-HP, Hôpital Bichat, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 1123 ECEVE, Paris, France.|Département Hospitalo-Universitaire FIRE, INSERM, U1123, CIC-EC 1425, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Département d'Hématologie, Hôpitaux Universitaires Paris Nord Val de Seine, AP-HP, Hôpital Bichat, Paris France.|Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.|INSERM, U1148, Paris, France.
authors.forename: Marie-Geneviève
authors.initials: MG
authors.lastname: Huisse
authors.affiliation: Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Bichat, Unité d'Immunologie, Auto-immunité et Hypersensibilités, Paris, France.|INSERM, UMR 996, UFR de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.|INSERM, U1148, Paris, France.|FACT (French Alliance for Cardiovascular clinical Trials).
authors.forename: Hélène
authors.initials: H
authors.lastname: Abergel
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.|INSERM, U1148, Paris, France.|Département de Biochimie, Hôpitaux Universitaires Paris Nord Val de Seine, AP-HP, Hôpital Bichat, Paris France.
authors.forename: Fathi
authors.initials: F
authors.lastname: Driss
authors.affiliation: Département d'épidémiologie et recherche clinique, CIC-EC 1425, AP-HP, Hôpital Bichat, Paris, France.
authors.forename: Toni
authors.initials: T
authors.lastname: Alfaiate
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Département d'Hématologie, Hôpitaux Universitaires Paris Nord Val de Seine, AP-HP, Hôpital Bichat, Paris France.|Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.|INSERM, U1148, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Ajzenberg
authors.affiliation: Département Hospitalo-Universitaire FIRE Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.|INSERM, U1148, Paris, France.|FACT (French Alliance for Cardiovascular clinical Trials).|National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects*; D003888:Desensitization, Immunologic / Q000379:methods*; D004342:Drug Hypersensitivity / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
keywords: Acute coronary disease; Antiplatelet therapy; Aspirin hypersensitivity; Desensitization