Varicella-zoster virus infection-associated venous thromboembolism: a scoping review of 55 cases

Abstract Background Varicella-zoster virus (VZV) infection is typically self-limiting, but in rare cases, it can be complicated by venous thromboembolism (VTE), including cerebral venous sinus thrombosis (CVST), deep vein thrombosis (DVT), and pulmonary embolism (PE). Currently, systematic summaries regarding its clinical characteristics, thrombophilia background, and prognosis are relatively limited. Methods We searched PubMed and China National Knowledge Infrastructure (CNKI) databases for reports and case series of confirmed cases from the establishment of the databases to April 2026. These documents were required to meet both criteria: a clearly diagnosed VZV infection (primary varicella, herpes zoster, or herpes zoster without rash) and imaging-confirmed VTE. Afterward, we used descriptive statistical methods to summarize the demographic characteristics of patients, types of VZV infection, locations of thrombosis, results of thrombophilia testing, treatment strategies, and prognosis. Results We included a total of 47 articles, encompassing 55 patients. The average age was 33.8 ± 22.6 years, with 67.3% being male and 70.9% having primary varicella. The average interval from rash onset to thrombus formation was 10.7 ± 5.3 days. Isolated CVST was the most common manifestation (40.0%), followed by isolated DVT (21.8%), isolated PE (9.1%), isolated thrombosis at other sites (1.8%), and multi-site thrombosis (27.3%). Among the 29 patients who completed thrombophilia testing, transient abnormalities (transient antiphospholipid antibodies and/or temporary reductions in protein S/C) accounted for 44.8%, genetic abnormalities accounted for 10.3%, and mixed abnormalities accounted for 10.3%. Antiviral combined with antithrombotic therapy was the main treatment strategy (58.2%). At discharge, 29.1% of patients achieved complete recovery (no symptoms and no further treatment needed), 63.6% achieved complete recovery requiring prophylactic treatment (no functional deficit but requiring long-term anticoagulation or antiepileptic therapy), and the overall good outcome rate was 92.7%, with no deaths. During follow-up (information available for 37 patients), the incidence of sequelae was 16.2%, predominantly post-thrombotic syndrome. Conclusions VZV-associated VTE primarily affects young males. Isolated CVST is the most common manifestation. Its core mechanism is closely related to the transient hypercoagulable state induced by the virus. Antiviral combined with antithrombotic therapy was associated with a good prognosis, but long-term sequelae cannot be ignored. Clinicians should maintain high vigilance, promptly identify and treat this complication.