Transcatheter Arterial Embolization as a Treatment for Life-Threatening Retroperitoneal Hemorrhage in COVID-19 Patients on Anticoagulant Therapy

Retroperitoneal hemorrhage is a possible complication that has been noticed in COVID-19 patients on anticoagulant therapy. The data related to treatment and outcomes in this condition are scarce. We present a case series of four COVID-19 patients with lumbar artery bleeding, who were treated with transcatheter arterial embolization using embolization particles. The procedure was executed without any complications, and hemostasis was achieved in all four patients. Despite the patients survived the procedure, one patient died due to respiratory failure three weeks after the procedure, and one died due to hypovolemic shock two days later. Considering the ongoing state of COVID-19 pandemic, it is essential to be aware of transcatheter arterial embolization as a safe and effective procedure for treating retroperitoneal hemorrhage in COVID-19 patients.


Introduction
COVID-19 is an acute, complex disease that is caused by SARS-CoV-2 infection which in its most severe forms results in the development of interstitial pneumonia and acute respiratory distress syndrome (ARDS) [1] [2]. Apart from ARDS, the high risk of thrombosis or bleeding in critically ill patients with COVID-19 has been noticed [3]. It was previously reported that direct SARS-CoV-2 infection of endothelial cells may be associated with hypercoagulability as well as diffuse blood clots (disseminated intravascular coagulation (DIC)) which are characterized by an increased risk of bleeding due to platelet and fibrinogen consumption [4]. DIC and large-vessel thrombosis have been linked to multisystem organ failure [5] [6]. To combat this hypercoagulable state, patients infected with COVID-19 should be properly anticoagulated to reduce ischemic risk. However, there are some evidence that anticoagulation treatment may cause life-threatening bleeding complications such as retroperitoneal hemorrhage [7] [8] [9].
It was published by Abate et al. that the incidence of spontaneous muscle hematoma is 3 -4 times higher in patients with COVID-19 compared to patients on anticoagulant therapy who were not infected with COVID-19 [10]. The same authors reported a mortality of 32.4%, indicating that the occurrence of spontaneous muscle hematoma significantly worsens the prognosis of patients with COVID-19 [10]. We present four cases of retroperitoneal hemorrhage due to lumbar artery bleeding in patients being treated with anticoagulant therapy, emphasizing the importance of rational use of anticoagulation in COVID-19 patients as well as the need of rapid radiological investigation and treatment of bleeding by transcatheter arterial embolization (TAE).

Case Presentation
We experienced four patients (1, 2, 3, and 4) with retroperitoneal bleeding due to usage of nadroparin calcium (fraxiparine) as anticoagulant treatment in COVID-19 pneumonia. At the moment of admission, all of the patients presented with fever and respiratory symptoms and they were diagnosed with COVID-19 by RT-PCR.
Patients' characteristics are presented in Table 1. a. CAD-coronary artery disease, HT-hypertension, DM-diabetes mellitus. b. The CT severity score is a scoring system used to assess the lung changes and involvement by COVID-19. It is based on visualization of changes characteristic of COVID-19 (ground glass opacities, vascular enlargement, consolidation, subpleural band, architectural distortion, crazy paving) using native CT examination. The total CT score is the sum of the individual lobar scores and can range from 0 (no involvement) to 25 (maximum involvement), when all the five lobes show more than 75% involvement. Open Journal of Emergency Medicine The patients included 2 men and 2 women (average age, 72 years). Patients were hospitalized due to COVID-19 pneumonia that was confirmed by CT scanning without intravenous contrast for three of them (1,2,3). Their CT severity scores were 23, 11, and 18, for 1, 2, and 3, respectively. Two patients (2,3) with previously diagnosed coronary artery disease were continued on aspirin and all four of them were started on prophylactic fraxiparine (5700 i.j./0.6 mL/daily s.c.) due to concern about COVID-19 induced hypercoagulable state.
Over    Two (2 and 3) of the four patients are still alive at one and two months, respectively, after the intervention. Unfortunately, patient 1 died due to hemodynamic instability two days after the intervention. Patient 4 remained in ICU due to COVID-19 pneumonia with a stable hemoglobin level and no further bleeding, but eventually died due to respiratory failure three weeks after the intervention.

Discussion
High mortality in patients suffering from COVID-19 as multi-systematic disease All 4 patients in our study survived TAE procedure, but one (1) died of ARDS induced by COVID-19 pneumonia, three weeks later. The death of another patient (1) was caused by bleeding-related cardiovascular failure, furthermore suggesting the significance of prompt radiologic investigation and intervention.
These findings are in agreement with recommendations regarding prompt angiographic management of retroperitoneal hemorrhage in COVID-19 patients, previously reported by Lucatelli et al. [8] [9]. Since the data related to retroperitoneal bleeding in COVID-19 patients and its management is very scarce, the presented and similar reports provide a significant contribution in this field.

Conclusion
Considering that COVID-19 pandemic has led to a dramatic loss of human life worldwide and presents an unprecedented challenge to public health, it is of great significance for clinicians to be aware of possible complications, such as retroperitoneal hemorrhage, and to be able to recognize the symptoms. Early radiological detection and proper treatment, such as TAE, is the way to lower mortality due to retroperitoneal hemorrhage.