Delayed hypersensitivity to new oral anticoagulants. Demonstration of cross reactivity for the drug category and definition of non-irritant concentrations for patch tests

Abstract

The current therapy with direct trombin inhibitors (DTI) is indicated for the prevention of stroke in non-valvular atrial fibrillation. Side effects are reported, particularly skin hypersensitivity, for this whole category of drugs as well as for other modern antiplatelet and anticoagulant drugs. For their clinical features, these reactions appear as delayed T-cell mediated drug hypersensitivity, but at present there are no diagnostic methods of investigation. We reported a case of delayed skin reaction to edoxaban and we found the non-irritant concentration for patch test in the whole category of drugs. The patch test resulted positive for edoxaban. A successive challenge with alternative DTIs and/or a switch to warfarin is proposed as alternative therapy.

Anti-Xa Inhibitor-Induced Hemorrhagic Pruritic Rash: A Case Report on Possible Cross-Reactivity Between Apixaban and Rivaroxaban

“…Possible cross-reactivity between factor Xa inhibitors has been reported previously in a patient that was challenged with apixaban 7 days after developing delayed hypersensitivity reaction to edoxaban. 14 Given apixaban’s half-life of about 12 hours, we could not definitively confirm that our patient developed cross-reactivity between factor Xa inhibitors since apixaban would not have been fully cleared when rivaroxaban was initiated. To our knowledge, this is the first case report of hypersensitivity to apixaban occurring within a few hours of receiving the first dose, suggesting that DOAC-induced hypersensitivity reactions are not always delayed.…”

A rare case report of apixaban-induced lichenoid eruption

“…However, it failed to identify cross reactivity to apixaban, indicating that a delayed reading of test at more than 5 days may be indicated. 11 Another recently published case report described rivaroxaban-induced urticaria and angioedema, with possible cross reactivity to dabigatran, manifested as rash in a 63-year-old male. 22 There is limited availability of information on the cross reactivity across different DOACs in the literature.…”

“…8 Availability of case reports describing apixaban-induced hypersensitivity reactions are limited, and very few, if any, describe experience on diagnostic or biopsy tests. 9 – 11 In addition, the cross reactivity across DOACs as a class is also unknown. To the best of our knowledge, there is currently no reported case of lichenoid eruption induced by apixaban.…”

Vasculitis leucocitoclástica secundaria a nuevos anticoagulantes orales

“…Solamente cuando el tratamiento anticoagulante fue sustituido por dabigatrán 5 se observó un empeoramiento de la clínica. Un estudio reciente ha demostrado la reactividad cruzada de dabigatrán con edoxabán mediante pruebas epicutáneas 8 , por tanto, quizás debería ser evitado en estos casos. Por el contrario, rivaroxabán parece no tener este problema 4,9 , por lo que junto a las heparinas podría ser una buena opción sustitutiva.…”