Abstract
COVID-19 infection is known to cause thromboembolic complications. This is why patients hospitalized with COVID-19 are put on prophylactic anticoagulation. We present the case of a Caucasian woman, aged 71 years, with risk factors of class 1 obesity, hyperlipidemia, and hypertension, initially admitted for COVID-19 pneumonia, and later developed acute mesenteric ischemia followed by pulmonary embolism. These incidents occurred while the patient was receiving high-dose prophylactic enoxaparin (40 mg twice daily). COVID-19 associated acute mesenteric ischemia is a complication with high mortality. Therefore, high suspicion, early recognition, and surgical management is necessary. Apart from that, this case emphasizes the question of whether there is a need for proactively administering therapeutic anticoagulation for high thrombotic risk COVID-19 patients to prevent deadly complications.
- Intestinal ischemia
- Cocaine
- Iatrogenic Disease
- In-Hospital Mortality
- Length of Stay
- Patient Outcome Assessment
COVID-19, also called acute respiratory syndrome coronavirus 2 SARS-CoV-2, was declared a pandemic in March 2020.1 COVID-19, though initially considered as a respiratory tract pathogen, can cause multiple organ dysfunction.2 Thromboembolic complications are being increasingly reported in COVID-19 pneumonia.3 The most known complications are deep vein thrombosis, pulmonary embolism, stroke, acute limb ischemia, and acute coronary syndrome. There have also been a few reports of acute mesenteric ischemia in patients with severe COVID-19 pneumonia.4 Here, we present a case of acute mesenteric ischemia in a COVID patient with a deadly outcome.
Case Presentation
A Caucasian woman, aged 71 years, unvaccinated against COVID-19, with a pertinent history of hypertension, hyperlipidemia, Class I obesity with a body mass index of 33.1 presented with complaints of myalgia and feeling feverish for 1 week. On presentation, she was saturating 63% on room air, and improved to 93% with 5 liters of supplemental oxygen through nasal cannula. She tested positive for COVID-19. Laboratory values were pertinent for D-dimer of 1076 ng/mL (reference range < 190-499 ng/mL). Computed tomography (CT) of the chest was negative for pulmonary embolism but was consistent with underlying new diagnosis of interstitial lung disease. She was admitted with a diagnosis of severe COVID-19, and was started on remdesivir and dexamethasone. She was also started on subcutaneous enoxaparin 40 mg twice daily for deep vein thrombosis prophylaxis. Overnight, the patient deteriorated with rapidly increasing oxygen requirements and was transitioned to non-invasive high-flow respiratory support system (“Vapotherm”). The patient remained stable on Vapotherm for the next few days.
On the fifth day, the patient started complaining of mild generalized abdominal spasms, however without any associated diarrhea, nausea, or vomiting. Physical examination showed a non-tender abdomen with positive bowel sounds, otherwise unremarkable. This was further evaluated with abdominal radiography, which was unremarkable. CT without contrast was obtained due to the patient’s history of allergy to contrast. The imaging could not identify significant abnormalities because of the lack of contrast. However, her D-dimer trended up to 7334 ng/mL, around 7 fold increase compared to presentation. There was an increasing trend in ferritin (from 222 ng/mL to 314 ng/mL, trending up to 599 ng/mL [reference range 26-252 ng/mL]); marked elevation in C-Reactive Protein (CRP) (from 2.0 mg/dL to 16.4 mg/dL, trending up to 18 mg/dL [reference range ≤1.0 mg/dL]); and procalcitonin (from <0.052 ng/mL to 0.38 ng/mL, trending up to 1.89 ng/mL). There was an increasing trend in white blood cell count, which increased from 11.7 × 103/uL at the time of admission to 29.4 × 103/uL (Table 1). The patient was given pre-medications for contrast allergy, and a repeat CT with contrast was performed on the sixth day. CT angiogram of the abdomen and pelvis with contrast done on the sixth day showed a filling defect in proximal and distal superior mesenteric artery, ileocolic territory, mild stenosis in the celiac axis origin, and moderate stenosis at the origin of the inferior mesenteric artery (Figures 1-4). Simultaneously, even the maximum settings of non-invasive ventilation were inadequate to support the patient. Hence patient was transferred to the intensive care unit (ICU) on the sixth day of hospitalization.
Difference in markers between the day of admission and onset of acute mesenteric ischemia
Sagittal view of the computed tomography angiography of the abdomen showing filling defect of superior mesenteric artery trunk with in situ thrombus or thromboembolus to the superior mesenteric artery. H, Headside; F, Footside; A, Anterior; P, Posterior
Coronal view of the computed tomography angiography of the abdomen showing filling defect of superior mesenteric artery trunk with in situ thrombus or thromboembolus to the superior mesenteric artery. SMA, Superior Mesenteric Artery; H, Headside; F, Footside; R, Right; L, Left
Coronal view of the computed tomography angiography of the abdomen showing filling defect of superior mesenteric artery trunk with further characterization of jejunal branches with the filling defect. SMA, Superior Mesenteric Artery; H, Headside; F, Footside; R, Right; L, Left
Transverse view of the computed tomography angiography of the abdomen showing filling defect of superior mesenteric artery trunk with in situ thrombus or thromboembolus to the superior mesenteric artery.
General Surgery and Vascular Surgery were consulted for mesenteric ischemia. The patient was intubated, and an emergency laparotomy was done. It was noted that approximately 70 cm of ileum was necrotic and was removed. Subsequently, a superior mesenteric artery embolectomy was performed, and the patient was transferred back to the ICU. The fascia was not closed in anticipation of further exploration. The patient was started on intravenous (IV) broad spectrum antibiotics including cefepime, vancomycin, and metronidazole. She was also placed on IV heparin drip and total parenteral nutrition. The patient’s activated plasma thromboplastin time (APTT) was monitored periodically to ensure adequate anticoagulation. Repeat CT of the chest showed significantly progressing pneumonia and small pulmonary embolism in the right middle lobe with no evidence of heart strain. Two days post procedure, the abdomen was further explored in the medical ICU with 3 cm to 4 cm of necrotic small bowel further resected. Three days after this prior procedure, a repeat surgery was performed, again with 8 cm of necrotic bowel removed bedside. This time, re-anastomosis was accompanied with closure of fascia. Pathology reports of the initial procedure showed a segment of benign bowel with ischemic or hemorrhagic necrosis with patent mesenteric vessels and viable mucosal margins. However, specimens collected on second laparotomy showed partial to near complete ischemic necrosis with non-viable margins, which meant the ischemia was progressing despite being on therapeutic heparin anticoagulation. This was in contrast to the patient’s D-dimer, which was trending down post-initiation of heparin. We were unable to wean the ventilator. Due to multi-system involvement and poor prognosis, the palliative care team was consulted and goals of care discussion was held. Decision was made to withdraw life-sustaining therapies. The patient expired after extubation (See Table 2 for summary of clinical course).
Summary of clinical course
Discussion
The exact pathophysiology behind this complication is still unknown. One of the initial case series from Wuhan, China, in which patients were having thromboembolic complications, reported the presence of anticardiolipin anti-IgA, anti-B2 glycoprotein IgA, and IgG.9 This hypothesized the possibility of anti-phospholipid syndrome as a potential etiology for thrombotic complications.9,10 Acute mesenteric ischemia to COVID-19 is mostly related to a state of hypercoagulability possibly explained by an interaction with angiotensin-converting enzyme (ACE) mediated inflammatory reaction.5,6 Enterocytes are rich in ACE2 receptors, which are a target receptor group for SARS-CoV-2. Interaction of SARS-CoV2 with enterocytic ACE2 receptors lead to decreased degradation of angiotensin II. This has two potential implications. Firstly, it could increase the production of IL-6, producing a massive inflammatory response with high cytokine release. Secondly, angiotensin II could increase the expression of tissue factor and plasminogen activator inhibitor-1 by the endothelial cells, leading to a hypercoagulable state.5,6 Acute mesenteric ischemia as a condition by itself has a high mortality, with mortality rates reaching 80%, even with surgical treatment without revascularization.11 This is regardless of being associated with COVID-19.
On admission, our patient did not have any abdominal symptoms or signs, and hence, there was no indication to image the abdomen on admission. Her abdominal symptoms started on the fifth day. The initial CT abdomen had to be done without IV contrast, as the patient had a contrast allergy. The patient had to be pre-medicated with steroids and CT angiogram with contrast could be done only after 13 hours, which came up with the positive findings. Two days later the patient was also found to have small pulmonary embolism despite initiation of heparin drip and maintaining it in the therapeutic range. This supports our inference that the thrombotic complications, including mesenteric ischemia, was likely an event that happened progressively post admission, despite providing thromboembolic prophylaxis for this patient. Hence, it is not likely an event that was present during the initial admission time. Exploratory laparotomy was performed thrice, and every time new necrosis was found in the bowel. This shows the significant extent of the hypercoagulability our patient experienced.
D-dimer levels and imaging studies, specifically CT angiogram of the abdomen and pelvis has a pivotal role in diagnosing mesenteric ischemia.7 In our patient, the new symptom onset of abdominal pain was accompanied by a seven-fold increase of D-dimer and around 8-fold increase of CRP. Even thickening, edema, and bowel dilatation >15 mm should raise suspicion for mesenteric ischemia.8 Having high suspicion for mesenteric ischemia whenever there is new abdominal pain or a new significant elevation in the inflammatory markers is necessary in managing patients with severe COVID. The patient in this case had mild symptoms of abdominal pain, although, we were able to get the correct diagnosis because of a high index of suspicion. However, this patient had an extensive hypercoagulability manifestation, even while being on prophylactic enoxaparin, and had extensive staged acute mesenteric ischemia manifestation, which, despite multiple surgeries and therapeutic anticoagulation, resulted in death.
In our patient, it is clear that prophylactic anticoagulation was ineffective in preventing acute mesenteric ischemia. One open label randomized controlled trial showed an initial strategy of therapeutic anticoagulation with heparin in non-critically ill patients increased the probability of survival by decreasing the need for organ support.12 Based on this study, consideration may be given to develop a standard guideline recommendation of therapeutic anticoagulation in non-critically ill COVID-19 patients, at least for the population with high D-dimer. This can limit the incidence of acute mesenteric ischemia in COVID patients with high thrombotic risk, as the development of this complication indicates high mortality.
Conclusion
Clinicians treating COVID-19 should have a high index of suspicion for thrombotic complications, and regular monitoring of coagulation profiles is necessary in management of COVID-19 positive patients, irrespective of risk factors. COVID-19 associated acute mesenteric ischemia is a complication with high mortality. Therefore, high suspicion, early recognition, and early surgical management is necessary. For patients with high thrombotic risk, as evidenced by elevated D-dimer, early therapeutic anticoagulation may be considered, even in non-critically ill patients, to limit thrombotic complications.
Acknowledgements
The authors wish to acknowledge Kristin M Gerndt, MD, Department of Radiology, Marshfield Clinic, Marshfield, WI for providing the radiology images.
Footnotes
Disclosure: The authors have reported no financial or personal conflicts of interest related to this work.
- Received March 3, 2022.
- Revision received August 17, 2022.
- Accepted September 26, 2022.
References
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