Systematic review of warfarin-induced skin necrosis case reports and secondary analysis of factors associated with mortality

Objective: Warfarin-induced skin necrosis (WSN) is a rare (0.0.1%-0.1%) and severe adverse reaction. The clinical characteristics of this reaction and its mortality rate have not been explored in a large population. Therefore, we present the case of a Peruvian patient who developed WSN and perform a systematic review of case reports of WSN. Methods: A systematic search was performed using the Pubmed/Medline, Scopus, Web of Science and Embase databases. Patient clinical data were collected and extracted from every case report. Furthermore, we analysed the factors associated with mortality because of WSN using the Poisson regression model with robust variations, obtaining risk ratios (RR) and their respective confidence intervals (95% CI). Results: We identified 90 case reports that included a total of 111 patients with WSN (mean age 52.5 years), 20.72% of whom died of complications because of WSN. Being male (RR: 2.87; 95% CI 1.21-6.83) and having three or more affected regions (RR: 6.81; 95% CI 2.62-17.74) were associated with an increased risk of death caused by WSN. Conclusion: This systematic review identified 90 case reports of WSN with three or more affected body regions. Male sex was associated with an increased risk of death. Further studies are needed to analyse and confirm these results.