Dabigatran Associated Leukocytoclastic Vasculitis

Potolidis, Evangelos; Mandros, Charalampos; Kotsa, Kalliopi; Mitsiou, Evdoxia; Potolidis, Dimitris; Fanourgiakis, Panagiotis

doi:10.1155/2015/616109

Cited by 18 publications

(17 citation statements)

References 5 publications

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“…Renal and hepatic adverse events are among the emerging DOAC safety issues [ 17 ]. Rare but severe skin adverse events, such as vasculitis, have also been reported in dabigatran-treated patients [ 19 – 21 ]. Furthermore, non-bleeding adverse events, including gastrointestinal symptoms such as dyspepsia, reported in dabigatran-treated patients [ 22 – 24 ], have been found to be one of the main reasons for permanent DOAC discontinuation.…”

Section: Introductionmentioning

confidence: 99%

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis

et al. 2018

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IntroductionPostmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases.ObjectiveThe aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA).MethodsSSA was performed using nationwide data from the French National Healthcare databases (Régime Général, 50 million beneficiaries) to assess a cohort of 386,081 DOAC new users for the first occurrence of four types of non-bleeding outcomes: renal, hepatic, skin outcomes identified by using hospitalization discharge diagnoses, and gastrointestinal outcomes by using medication reimbursement. Asymmetry in the distribution of each investigated outcome occurring before and after initiation of DOAC therapy was used to test the association between DOAC therapy and these outcomes. SSA inherently controls for time-constant confounders, and adjusted sequence ratios were computed after correcting for temporal trends. Negative (glaucoma) and positive (bleeding, depressive disorders) control outcomes were used and analyses were replicated on a cohort of 310,195 patients initiating a vitamin K antagonist (VKA).ResultsThis study demonstrated the expected positive association between either DOAC or VKA therapy and hospitalised bleeding and initiation of antidepressant therapy, while no association was observed between either DOAC or VKA therapy and initiation of antiglaucoma medications. For DOAC therapy, signals were the associations with hepatic outcomes, including acute liver injury [for the 3-month time window, aSR3 = 2.71, 95% confidence interval (CI) 1.79–4.52]; gastrointestinal outcomes, including initiation of drugs for constipation and antiemetic drugs (aSR3 = 1.31, 95% CI 1.27–1.36; and 1.17, 95% CI 1.12–1.22, respectively); and kidney diseases (aSR3 = 1.33, 95% CI 1.29–1.37).ConclusionResults of this nationwide study suggest that DOACs are associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded.Electronic supplementary materialThe online version of this article (10.1007/s40264-018-0668-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis

et al. 2018

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“…An eczematous drug eruption also was reported in a woman aged 71 years with atrial fibrillation with palmar and plantar involvement 11. To the best of our knowledge, there have been only two reported cases of dabigatran-related LCV: Cakmak et al 12 discussed a woman aged 74 years developing LCV within a week of dabigatran usage, and Potolidis et al 13 reported a case in a man aged 70 years in less than a week of initiation of dabigatran. Both cases were treated with systemic steroids and were switched to other forms of anticoagulation including low molecular heparin and warfarin.…”

Section: Discussionmentioning

confidence: 99%

Dabigatran-related leukocytoclastic vasculitis

An¹,

Garje

Wanat

et al. 2017

BMJ Case Reports

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Dabigatran is a non-vitamin K antagonist oral anticoagulant that has been approved for atrial fibrillation and prevention of venous thromboembolism. Its use has been increasing in the USA since serum drug levels do not need monitoring. To date, no significant skin side effects have been reported other than 4 cases of non-specific skin lesion and 2 cases of leukocytoclastic vasculitis (LCV), which is a small vessel inflammatory disease that presents as palpable purpura in lower extremities. We present a man aged 57 years with chronic deep vein thrombosis who developed palpable purpura, petechiae, swelling in lower extremities, torso and distal upper extremities on the third day after dabigatran initiation. The present case highlights the potential risk for LCV with dabigatran use and provides insight into its management.

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“…A possible explanation for this relatively frequent side effect may be related to drug chemical structure as an aromatic amine (36). Three leukocytoclastic vasculitis case reports were found (37,38,39) developing within the first week of treatment with dabigatran with typical purpuric macules, distribution to limbs, back and trunk, and shared histopathologic findings of neutrophilic infiltration, red cell extravasation and fibrin deposition within vessel walls. In the case described by An J. and colleagues (37) cutaneous vasculitis was associated with peripheral blood eosinophilia and elevation of inflammatory markers.…”

Section: Hypersensitivity Reactions To Dabigatranmentioning

confidence: 99%

Hypersensitivity reactions to non-vitamin K oral anticoagulants - a review of literature and diagnostic work-up proposal

Carli

Farsi

Chiarini

et al. 2019

Eur Ann Allergy Clin Immunol

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Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly being used in hospital and outpatient settings as safe alternatives to warfarin. Hypersensitivity reactions have been described for NOACs and can be classified according to Gell and Coombs. We reviewed case reports of possible drug hypersensitivity reactions, noticing a predominance of delayed reactions (both mild and severe) and the absence of cross-reactions to warfarin and low molecular weight heparins. International experience on diagnostic tests is lacking. The vast majority of authors refer to probability scores and rely on biopsy to classify vasculitis and rule out differential diagnoses. We propose to adapt available tests to confirm the patient's reactivity to new anticoagulants. Among in vivo tests, patch testing revealed promising in delayed reactions.

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Dabigatran Associated Leukocytoclastic Vasculitis

Cited by 18 publications

References 5 publications

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis

Dabigatran-related leukocytoclastic vasculitis

Hypersensitivity reactions to non-vitamin K oral anticoagulants - a review of literature and diagnostic work-up proposal

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