Dataset Information

A Case Report of Rivaroxaban-Induced Urticaria and Angioedema With Possible Cross-Reaction to Dabigatran.

ABSTRACT: Anticoagulants are commonly associated with hemorrhagic complications. However, rare hypersensitivity drug reactions associated with direct oral anticoagulants (DOACs) in form of cutaneous reactions such as urticaria as well as angioedema can have significant burden owing to increase in morbidity and mortality. Angioedema can be allergic, hereditary or idiopathic and can occur in isolation, in combination with urticaria as contributing component of anaphylaxis. With increase in the use of DOACs over warfarin as choice of anticoagulant in the treatment of atrial fibrillation (AF) as well as venous thromboembolism (VTE), recent post marketing surveillance has identified several reports of adverse drug reactions. This case report describes the clinical course of patient being treated for VTE, who experienced rivaroxaban-induced urticaria and angioedema. We further provide evidence for cross-reactivity to dabigatran manifested as significant cutaneous reaction. Patient was transitioned to warfarin with enoxaparin bridge and tolerated it well without any complications.

SUBMITTER: Patil T

PROVIDER: S-EPMC8383569 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A Case Report of Rivaroxaban-Induced Urticaria and Angioedema With Possible Cross-Reaction to Dabigatran.

Patil Tanvi T Ikekwere Christina C

Journal of medical cases 20191231 12

Anticoagulants are commonly associated with hemorrhagic complications. However, rare hypersensitivity drug reactions associated with direct oral anticoagulants (DOACs) in form of cutaneous reactions such as urticaria as well as angioedema can have significant burden owing to increase in morbidity and mortality. Angioedema can be allergic, hereditary or idiopathic and can occur in isolation, in combination with urticaria as contributing component of anaphylaxis. With increase in the use of DOACs ...[more]

PMID: 34434309

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Project description:Background: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA). Objectives: To characterize the transcriptomic and metabolomic profiles of NIUA patients undergoing aspirin desensitization. Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were separated from the blood of NIUA patients undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls. RNA was isolated from PBMCs and subjected to mRNA- and lncRNA-seq. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semi-targeted metabolomics panel. Results: Eleven patients with NIUA and 10 healthy controls were recruited. The mRNA gene profiles of pre- versus post-desensitization and healthy control versus post-desensitization did not differ significantly. However, we identified 739 mRNAs and 888 lncRNAs as differentially expressed from pre-aspirin desensitization patients and controls. A 12-mRNA gene signature was trained using a machine learning algorithm to distinguish between controls, post-dose and pre-dose samples. Ingenuity Pathway Analysis identified 5 canonical pathways that were significantly enriched in pre-aspirin desensitization samples. Interleukin (IL)-22 was the most upregulated pathway. To investigate the potential regulatory roles of the differentially expressed lncRNA on the mRNAs, 9 lncRNAs and 12 mRNAs showed significantly correlated expression patterns in the IL-22 pathway. To validate the transcriptomics data, IL-22 was measured in the plasma samples of the subjects using ELISA. IL-22 was significantly higher in pre-aspirin desensitization patients compared to controls. In parallel, metabolomic analysis revealed stark differences in plasma profiles of pre-aspirin desensitization patients and healthy controls. In particular, 2-hydroxybenzoic acid (salicylic acid) was significantly lower in pre-aspirin desensitization patients compared to healthy controls. Conclusion: This is the first study to combine both transcriptomic and metabolomic approaches in patients with NIUA, which contributes to a deeper understanding about the pathogenesis of NIUA and may potentially pave the way towards a molecular diagnosis of NSAID hypersensitivity.

Project description:BackgroundVitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These agents have been mainstays of anticoagulation for people older than 60 years. However, their administration is associated with a risk of bleeding and requires careful monitoring of patients. Novel oral anticoagulants (NOACs), such as dabigatran, are significantly safer in preventing thromboembolism than warfarin and heparin (sporadically causes thrombocytopenia) and are more specific for their target protein, thrombin. The major advantage of dabigatran, a direct thrombin inhibitor, is that it reversibly inhibits both free and clot-bound thrombin by tight binding affinity and the predictable pharmacodynamic effect. A few studies, however, reported that dabigatran can cause thrombocytopenia, although the underlying mechanism remains unclear. Thus, an antidote for dabigatran was developed to prevent thrombocytopenia.Case presentationIn this report, we discuss two cases of thrombocytopenia and purpura after dabigatran treatment. A 73-year-old man showed hemorrhagic necrotic skin lesions on his neck and right hand. He was administered dabigatran (220 mg/day) for cerebral infarction for three days and his platelet count decreased abruptly (6000/μL). This suggested that dabigatran had caused thrombocytopenia and purpura; therefore, dabigatran administration was discontinued. The results of a blood test, performed 14 days after stopping dabigatran treatment, showed that the platelet count had recovered to the normal range of more than 150,000/μL. A 75-year-old woman had taken warfarin continuously for 8 years. However, she had a new cerebral infarction. Therefore, warfarin treatment was replaced with dabigatran (300 mg/day). Her platelet count decreased (41,000/μL) significantly and dabigatran treatment was discontinued. The blood test results show that platelet counts gradually recovered to the normal range.ConclusionsDabigatran application may cause bleeding; therefore, careful monitoring during dabigatran treatment is required to prevent thrombocytopenia. An explanation is that the interaction of dabigatran with thrombin, because of its strong binding affinity, may cause the observed thrombocytopenia.

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Dataset Information

A Case Report of Rivaroxaban-Induced Urticaria and Angioedema With Possible Cross-Reaction to Dabigatran.

Publications

A Case Report of Rivaroxaban-Induced Urticaria and Angioedema With Possible Cross-Reaction to Dabigatran.

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