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Due to the respiratory infection of SARS-CoV-2, COVID-19 pandemic has now become a global threat (1-4). Numerous papers have addressed the pulmonary symptoms of this disease which highly contributed to the identification of the pathogenesis of COVID-19 infection. It seems that ACE2 receptors are involved in the entrance of the virus into the cells. Regarding the presence of these receptors on the surface of the alveoli epithelial cells and vascular endothelium, these cells and organs are prone to this virus (5). The incidence of thrombotic complications such as Pulmonary Thromboembolism, deep vein thrombosis, ischemic stroke, cardiac infarction, and arterial embolism is high in COVID-19 patients which has been reported in numerous studies before (6, 7). The initial clinical sign of coagulopathy in COVID-19 is organ failure while hemorrhagic complications are less common. The changes in the hemostatic markers such as D-dimer and fibrin and fibrinogen products have indicated that the basis of the coagulopathy is probably the fibrin products (8). However, the hemorrhagic complications of COVID-19 patients have received less attention. In this context, the current study presents four COVID-19 patients with hemorrhagic complications and describes their treatments.
This paper investigates four COVID-19 patients with hemorrhagic complications (female; with a mean age of 48). All four patients had positive PCR tests for COVID-19 and exhibited bilateral pulmonary involvement with typical COVID-19 pattern (CORADS=6).
These patients were admitted in the ICU and received routine COVID-19 treatments. None of them received mechanical ventilation or intubation and they were treated under the guideline of the hospital in the ICU. Regarding the risk of thrombotic events, all four patients received a prophylactic dose of heparin.
During hospitalization, all four cases had rectus sheath hematoma and retroperitoneal hemorrhage. The first patient was about to recover and changed from CBR (Complete Bed Rest) to RBR (Relative Bed Rest) condition. Following the physical activities, the patient fell and fainted. Regarding the declined consciousness and faint, she was investigated. She had abdominal and pelvic ultrasonography due to the bruising in the anterior parts of the abdomen. Further investigations showed rectus sheath hematoma and accumulation of loculated fluid in the retroperitoneum (Figure 1). In these patients, due to hemorrhage in the rectus sheath and retroperitoneum, surgical treatment was not the choice and endovascular treatment was selected. Therefore, to control the hemorrhage, the patients underwent a less invasive intervention (arterial embolization) according to the volume of the hem-orrhage and their conditions. Subsequently, three other patients with the same symptoms but in CBR status, experienced symptoms of volume reduction and shock. Further investigations indicated declined hemoglobin followed by hemorrhage in the rectus sheath and retroperitoneum who also received arterial embo-lization.
Figure 1. Massive rectus sheath hematoma in contrast enhanced abdominopelvic CT
Inferior epigastric artery and anterior trunk of internal iliac artery embolization was performed under fluoroscopic and angiographic guidance (Figure 2 and 3). Active bleeding of patients was controlled. Three patients were discharged from the hospital after completing the appropriate course of treatment. One patient, unfortunately, died due to the severity of pulmonary involvement caused by COVID- 19 due to her advanced age and volume of hemorrhage.
Figure 2. DSA Angiography of pelvic arterial system, multiple foci of bleeding in pelvic floor
representing as extravasation in Internal Iliac Artery Territory
Figure 3. Selective Angiography, arterial blush in the territory of inferior epigastric artery shows the bleeding site
Coagulation-anticoagulant imbalance during the immune response to the virus leads to overproduction of inflammatory cytokines and multi-organ failure. Initially, since all four patients were treated with a prophylactic dose of heparin, their hemorrhage was attributed to heparin-induced hemorrhagic com-plications. Due to falling of the first patient, it was also suggested as a cause of hemorrhage in the patient. However, the volume of bleeding and the symptoms caused by volume loss was not justifiable with the side effects of the prophylactic dose of heparin in the literature review (9, 10). The other three patients also had a hemorrhage in the CBR state, which also further declined the chance of falling as the underlying cause of hemorrhage. Gradually attention was paid to the incidence of coagulopathy in COVID-19 patients. The occurrence of these symptoms and hemorrhage in patients can be justified in the setting of coagulopathy in COVID-19 patients. The retrograde evaluation of the first patient indicated a gradual decrease in hemoglobin level, which also suggests that the patient's falling could also be due to the decrease in hemoglobin level. Although venous thromboembolism and arterial thrombosis are more common in COVID-19 coa-gulopathy, in some cases, the clinical symptoms overlap with hemophagocytic syndromes, antiphospholipid, and thrombotic microangiopathies (11). The use of heparin prophylaxis is still controversial in COVID-19 patients. Cerebral hemorrhage has also been reported in COVID- 19 patients, some of which have been secondary to prophylactic use of heparin. Several guidelines have been developed and employed for the treatment and management of coagulopathy and thrombotic complications in COVID-19 patients (12). Numerous studies have addressed the mechanism and pathogenesis of thrombotic and hemorrhagic complications of COVID-19; however, further inves-tigations are required to clarify the role of effective factors and complications of coagulopathy in patients with COVID-19 and their appropriate treatment (12, 13). It may also be possible to prevent hemorrhagic and thrombotic complications in patients by evaluating coagulation tests during hospitalization and before discharge, which also requires further investigations.
There is increasing awareness of coagulation disorders in Covid-19 infection. Thrombotic complications seem to be common among this patient population, which may necessitate preparing appropriate guidelines for its management. However hemorrhagic complications and their proper treatment should also be taken into consideration in covid-19 infection.
Hereby I would like to thank and appreciate Iran University of Medical Sciences for cooperation in the stages of the project.
This research did not receive any specific grant.
Authors declared no conflict of interests.
All ethical standards are met in this study.
A written consent was obtained from the patient.
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