(1) Background: Spontaneous retroperitoneal hematomas are a relatively common occurrence in hospitalized patients with COVID-19 related pneumonia, and endovascular treatment of trans-arterial embolization (TAE) may be a life-saving procedure after failure of medical and supportive therapy. The aim of our study was to evaluate spontaneous retroperitoneal hematomas in the COVID-19 era, focusing on their imaging features at CTA and DSA and on the safety, as well as technical and clinical success, of TAE, comparing patients affected by COVID-19 and non-COVID-19 patients. (2) Materials and Methods: We retrospectively enrolled 24 patients with spontaneous retroperitoneal hematoma who underwent TAE; of these, 10 were hospitalized for COVID-19-related pneumonia, while the other 14 were without COVID-19 infection. We evaluated the demographic data, hemoglobin values before and after the procedure, preprocedural aPTT, preprocedural INR, diagnostic and interventional imaging findings, procedural outcome (technical success) and survival periprocedural (clinical success), and major and minor complications. (3) Results: The mean age of the study population was 72.7 ± 11.2 years. CTA revealed signs of active bleeding in 20 patients (83%). DSA showed signs of active bleeding in 20 patients (83%). In four patients (17%), blind embolization was performed. The overall technical success rate was 100%. Clinical success was achieved in 17 patients (71%), while seven patients (29%) rebled within 96 h, and all of them were retreated. No major periprocedural complication was reported. The comparison between the two groups did not show statistically significant differences for gender, mean age, mean pre- and postprocedural hemoglobin, aPTT and INR, mean hematoma volume (cm3
), or mean delay between CT and DSA. Active bleeding at CTA was detected in 90% of COVID-19 patients and 79% of non-COVID-19 patients (p
= 0.61). At DSA, active bleeding was assessed in eight out of 10 (80%) patients in the COVID-19 group and 12 out of 14 (86%) patients in the non-COVID-19 group (p
= 1). Technical success was obtained in 100% of patients in both groups. Clinical success rates were 70% for COVID-19 group and 71% for the non-COVID-19 group. We found no statistical significance between the clinical success rates of retroperitoneal spontaneous hematoma embolization in patients with or without SARS-CoV-2 infection. (4) Conclusions: We suggest that, similar to what has been reported in other studies in non-COVID-19 patients, TAE should be considered an important safe, effective, and potentially life-saving option for the management and the treatment of patients affected by COVID-19 who present with spontaneous retroperitoneal hematoma and who could not benefit from conservative treatment.
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