warfarin and Stevens-Johnson-Syndrome

In this review, we discuss the potential expectations, validity, predictive ability, and reality of pharmacogenetics in (1) titration of medication dose, (2) prediction of intended (efficacy) drug response, and (3) dose prediction of unintended (adverse) drug response. We expound on what these potential genetic predictors tell us and, more importantly, what they cannot tell us. Although pharmacogenetic markers have been hailed as promising tools, these proclamations are based mainly on associations rather than their evaluation as predictors. To put the expectations of the promise of pharmacogenetics in a realistic perspective, we review three examples. First, warfarin pharmacogenetics, wherein although the validity of the genetic variant dose is established and there is a validity of genetic variant-hemorrhage association, the clinical utility of testing is not clear. Second, the strong and clinically relevant HLA-Stevens-Johnson syndrome/toxic epidermal necrolysis association highlights the role of ethnicity. Third, the influence of CYP2D6 on tamoxifen efficacy, a model candidate with potential clinical utility but unclear validity. These examples highlight both the challenges and opportunities of pharmacogenomics. First, establishing a valid association between a genetic variation and drug response; second, doing so for a clinically meaningful outcome; and third, providing solid evidence or rationale for improvement in patient outcomes compared with current standard of care.

Topics: Anticoagulants; Antineoplastic Agents, Hormonal; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Genetic Variation; Genotype; Hemorrhage; Humans; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine; Stevens-Johnson Syndrome; Tamoxifen; Warfarin

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe disorders, characterized by necrosis and epidermal detachment. Most important known acquired etiological factor is medications. Warfarin is one of the most common medications of cardiac valve surgery, which may rarely cause SJS or TEN. From this perspective, Aortic Valve Neocuspidization (AVNeo) procedure may be a good treatment option for such kind of patients, with a unique advantage of anticoagulation free postoperative course. In this report we aimed to share a patient with warfarin-induced STS/TEN, who was successfully treated with AVNeo procedure and mitral valve replacement.

Topics: Aortic Valve; Humans; Stevens-Johnson Syndrome; Warfarin

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening mucocutaneous disease that is predominantly drug-induced. Warfarin is the most commonly used drug for long-term anti-coagulant therapy; however, warfarin-induced SJS/TEN is seldom reported. In this study, we presented the case of a 61-year-old man who developed SJS after receiving multiple-drug therapy following aortic valve replacement surgery. The patient was diagnosed with drug-induced liver injury (DILI) based on significantly abnormal liver function test results. Warfarin was identified as the culprit drug using the algorithm of drug causality for epidermal necrolysis (ALDEN) score, enzyme-linked immunospot (ELISPOT) assay, and Roussel Uclaf Causality Assessment Method (RUCAM). After warfarin discontinuation and corticosteroid therapy, the lesions and liver function test findings improved. Human leukocyte antigen typing was conducted to detect the risk allele. To our knowledge, this is the first reported case of warfarin-induced SJS/TEN with DILI. This case suggests that commonly used and safe pharmaceutical agents such as warfarin can potentially cause serious adverse events, including SJS/TEN and DILI. The application of ALDEN, the ELISPOT assay, and RUCAM could be useful in identifying culprit drugs.

Topics: Algorithms; Chemical and Drug Induced Liver Injury; Humans; Male; Middle Aged; Stevens-Johnson Syndrome; Warfarin

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare diseases that cause acute destruction of the epithelium of the skin and mucous membranes, almost always attributable to drugs. However, warfarin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis is extremely rare. We report the case of 71-year-old woman who died due to destructive erosion all over her skin and mucous membranes. She had received a mitral valve prosthesis, and warfarin was prescribed for antithrombotic therapy. A lymphocyte transformation test for drug hypersensitivity and the clinical history confirmed this phenomenon as warfarin-induced toxic epidermal necrolysis.

Topics: Aged; Anticoagulants; Fatal Outcome; Female; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Mitral Valve Insufficiency; Stevens-Johnson Syndrome; Warfarin

Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN.. We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications.. To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

Topics: Anticoagulants; Child, Preschool; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; IgA Vasculitis; Methylprednisolone; Stevens-Johnson Syndrome; Warfarin