Clinical case

In September 2020, a 62-year-old man was admitted in our hospital owing to severe diffuse abdominal pain for three days associated with nausea, vomiting and a peak fever of 38.5°C. He had been using ceftriaxone and metronidazole for two days. He initially presented with diarrhea but progressed to develop inability to eliminate gas and feces. He had been hospitalized 20 days ago due to pneumonia caused by CO VID-19, diagnosed by RT-PCR of SARS-CoV-2, with 80% pulmonary involvement, when he was administered amoxicillin 1500 mg and dexamethasone 8 mg per day, both intravenous, for seven days. The patient also received Enoxaparin 60 mg twice daily subcutaneously for 5 days. The biological marker D-dimer was not measured during hospitalization. When ad mitted to the emergency unit, after almost three weeks after the onset of condition, he had a flat, semi-distended abdomen with reduced bowel sounds, diffuse pain on palpation, with no signs of peritoneal irritation.

Abdominal computed tomography showed signs of intes tinal occlusion, but without identification of an obstructive factor. In addition, it revealed the presence of a thrombus in the middle third of the superior mesenteric artery, 5.5 cm away from the abdominal aortic ostium with partial obstruc tion of the lumen and without signs of hypoperfusion in the intestinal loops (Fig. 1).

Fig. 1 At the top, axial abdominal computed tomography with contrast in the arterial phase. The arrow shows a filling defect (embolus) within the superior mesenteric artery. It is associated with slight densification of adjacent fat. Below, sagittal abdominal computed tomography with contrast in the arterial phase. The arrows point to: (A) the superior mesenteric artery and (B) an embolus inside the superior mesenteric artery. 

He underwent exploratory laparotomy due to the diagnostic hypothesis of vascular acute abdomen (mesenteric ischemia), with evidence of ischemia in the jejunum segment, 60 cm from the Treitz angle and without any signs of perforation or other complications. The superior mesenteric artery and jejunal branches were dissected and noticed to be pulseless. Throm boembolectomy was performed, with the clearance of a large amount of material compatible with the embolus/thrombus, resulting in a good pulse after the procedure. Enterectomy of 40 cm segment of the small bowel and primary anastomosis (entero-enteroanastomosis) were performed, and the obtained specimens were sent for histopathological examination.

Microscopic evaluation of the embolectomy product re vealed a recent blood thrombus (Fig. 2) that was predominant ly fibrinous. Evaluation of the enterectomy product revealed a segment of the small intestine with extensive mucous infarction and the foci of transmural infarction (Fig. 2). Intense acute peritonitis was found, along with increased collagen deposition in the lamina propria, which indicated chronic ischemic enteri tis. The clinical picture was suggestive of chronic ischemia followed by acute infarction.

The patient was discharged nine days after his admission, using rivaroxaban 20mg orally, daily. After about two months, he developed anasarca, hyporexia and abdominal pain in addition to hipoalbuminemia. He was diagnosed with short bowel syndrome. The patient showed significant clinical and nutritional improvement after dietary adjustments, and he is currently under outpatient follow-up with a serum albumin level of 4,3g/dL at the time of writing this report.

Fig. 2 At the top, mesenteric blood vessel filled by solidified fibrin with erytrocytes entrapped within forming a thrombus utilizing hematoxylin and eosin stains (100X). Below, extensive coagulative necrosis of the intestine, hemorrhage and acute inflammatory reaction consistent with transmural intestinal infarction (40X). 

In compliance with the Declaration of Helsinki and ethi cal standards of Brazil, this project was approved by the Research Ethics Committee of the Clinical Hospital - Federal University of Triângulo Mineiro, according to the Brazilian National Health Council resolution no. 466/2012, which deals with human research (CAAE 52716721.8.0000.8667; Approval no. 5.105.301). Written informed consent was obtained from the patient for publication of this case report.

Discussion

The COVID-19 pandemic is a new and rapidly evolving global public health problem. Therefore, reports on the unique aspects of this disease are crucial to help profes sionals in the management of infected patients¹.

Thrombotic complications associated with COVID-19 have been widely described, mainly venous thromboem bolic events. Arterial thrombosis has also been reported, but its prevalence is not well known. At any rate, such reports support the notion that COVID-19 promotes a hypercoagulable state in the body^1,3.

During the SARS-CoV-1 epidemic between 2002-2004, the reported incidence rates of deep vein thrombosis and pulmonary thromboembolism were 20% and 11%, respectively. In comparison, the incidence of thrombotic complications in patients with COVID-19 has been re ported to be as high as 79%³. In an autopsy study of 12 patients who died from COVID-19, a high incidence of deep vein thrombosis (58%) was found. Furthermore, diffuse alveolar damage was demonstrated by histology in 67% of cases². In a Dutch study of 184 critically ill patients with COVID-19, 31% developed thrombotic complications, with pulmonary thromboembolism being detected in 27% of cases and ischemic stroke in 3.7%⁴.

COVID-19-related hypercoagulability is likely to have a multifactorial etiology. First, it is related to viral aggres sion on the endothelial cells, which leads to inflammation and an increase in pro-coagulant factors, such as factor VIII, von Willebrand factor and fibrinogen. Moreover, it is associated with a storm of cytokines that trigger coagu lation and activation of fibrinolysis^1,2. Second, additional factors associated with hypercoagulability may be related to the presence of circulating prothrombotic microvesicles, consisting of nuclear DNA, histones, and nucleosomes, identified as cytoplasmic microparticles derived from platelets, monocytes, or neutrophils^2,3. A third possible mechanism involves the of angiotensin-converting enzyme 2 (ACE-2) receptors used by the virus to entry in human cells, including endothelial, lung and enterocyte cells, that triggering the same inflammatory phenomenon mentioned above⁵. In addition, there is an increase in the levels of angiotensin-II, which also exerts prothrombotic effects, including vasoconstriction and platelet and endothelial activation⁶.

This article reports a case of acute mesenteric ischemia in a post-COVID-19 patient, which is considered a severe and rare abdominal emergency, usually requiring an ur gent surgical approach and a wide intestinal resection. A prompt diagnosis is essential for successful treatment¹. Delays in the diagnosis of acute mesenteric ischemia are common and are associated with high rates of morbidity and mortality. Prompt diagnosis requires a high index of suspicion and early contrast-enhanced computed tomography imaging¹. Treatment of this condition relies on gastrointestinal decompression, fluid resuscitation, hemo dynamic support, surgical resection of the necrotic bowel, and restoration of blood flow to the ischemic intestine. The diagnosis of an ischemic bowel should be one of the top differentials in critically ill patients when clinical symptoms are suggestive¹. Mesenteric venous thrombosis is a rare condition, estimated to occur in 0.002-0.06% of all hos pital admissions. Unlike mesenteric arterial thrombosis, it is associated with prothrombotic and primary states of hypercoagulability. Thrombosis in atypical sites associated with COVID-19 has also been described, however, the frequency of its occurrence is not known.^7-11.

Early evaluation of abdominal vessels in COVID-19 patients who present with abdominal symptoms should be considered, especially when there is an elevated D-dimer level, as early treatment of thrombosis with low-molecular-weight heparin can have a significant impact on the therapeutic outcome⁶.

The present case supports the hypothesis of a hyper coagulable state related to COVID-19. Current treatment recommendations include the prophylactic use of low mo lecular weight heparin, which also has anti-inflammatory properties and is recommended by several international guidelines^3,4.