Authors: Mahmoud Mohamed,a,⁎Mahmoud Nassar,bNso Nso,b and Mostafa Alfishawyc
Arab J Gastroenterol. 2021 Jun; 22(2): 177–179.Published online 2021 May 14. doi: 10.1016/j.ajg.2021.05.00 8PMCID: PMC8118668PMID: 34090835
Abstract
Despite the emerging data about the thrombophilic effect of the novel coronavirus [1] , the relation between coagulation disorders and the COVID-19 pandemic is still not well understood. Various studies pointed to the significant role of the COVID-19 induced cytokine storm in development of the hypercoagulable state which leads to serious thromboembolic complications [2], [3] . Some studies report the development of severe immune thrombocytopenia induced by the novel coronavirus [4] . Other studies found a correlation between COVID-19 disease and the development of disseminated intravascular coagulation (DIC) [5].
Patients with severe COVID-19 disease have an increased risk for development of gastrointestinal bleeding (GI) which may be related to stress [6] , critical illness or mechanical ventilation [7] . Further studies showed the ability of the novel coronavirus to infect the epithelial cells of the GI tract [8] . Moreover, some data pointed to the ability of the virus even to infect the endothelium of blood vessels [9]. The relation between the COVID-19 pandemic and GI bleeding deserves more studies [10]. We present a case of GI bleeding in a patient with severe COVID-19 disease. We assume that COVID-19 disease can be a predominant factor for the development of DIC and GI bleeding.
Introduction
The prothrombotic outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have already been extensively reported [1]. However, the pathophysiology that may help elucidate the clinical correlation between coagulation disorders and the coronavirus disease 2019 (COVID-19) remains unclear. According to several clinical studies, COVID-19-induced cytokine storm might trigger hypercoagulable state and thromboembolic events [2], [3]. The impact of COVID-19 on immune thrombocytopenia development is also emphasized [4]. In addition, a strong correlation is presumed to exist between COVID-19 and disseminated intravascular coagulation (DIC) [5].
Moreover, gastrointestinal (GI) bleeding in COVID-19 increases the risk of irreversible stress [6], critical illness, or mechanical ventilation [7]. COVID-19 might invade the epithelial cells of the GI tract [8]. Several clinical data highlighted the ability of COVID-19 to infect the endothelial cells [9]. However, current clinical studies have not unraveled the mechanisms responsible for inducing GI bleeding in patients with COVID-19 [10]. Here, we present a case of GI bleeding in a patient with severe COVID-19. Our findings will encourage the scientific community to validate the presumed clinical correlation between COVID-19 and DIC/GI bleeding.Go to:
Case presentation
A 75-year-old African-American male patient arrived in the emergency room with fever, cough, and nausea, preceded by malaise for 2 weeks. He had a past medical history of insulin-dependent diabetes, hypertension, and dyslipidemia. He received treatment for his symptoms and was discharged with a follow-up prescription. After 3 days, he re-developed shortness of breath, thereby readmitted for further treatment. Chest x-ray revealed interval worsening of bilateral, predominantly bibasilar, interstitial, and alveolar opacities.
Acute respiratory distress syndrome occurred; thus, supplemental oxygen therapy, intubation, and medical management were provided. The reverse transcription–polymerase chain reaction (RT-PCR) test revealed that he was positive for COVID-19. The medical management relied on azithromycin combined with hydroxychloroquine. However, acute renal failure developed in a few days; thus, he received heparin-free continuous renal replacement therapy (CRRT). After 9 days, he was extubated. When his renal function markedly improved, he was transferred to the medicine floor.
Within a week of receiving CRRT, the patient developed hematochezia and became hemodynamically unstable. In the intensive care unit (ICU), he was assessed and diagnosed with hemorrhagic shock requiring massive blood transfusion, intubation (for airway protection), and inotropic support. Contrast-enhanced abdominal and pelvic computed tomography (CT) revealed bibasilar airspace disease in scanned lung zones and a fat-containing ventral abdominal wall hernia with bowel loops. The diagnostic assessment excluded the possibility of incarceration and active GI bleeding. Thereafter, the patient underwent resuscitation in the ICU, followed by a repeat CT assessment, which ruled out the development of bleeding episodes.
Unfortunately, the bleeding reoccurred; hence, an interventional radiologist initiated a pelvic arteriography. The inferior mesenteric artery angiogram and superior rectal artery (SRA) angiography did not indicate any active contrast extravasation. The patient, however, underwent transcatheter gel-foam embolization of the SRAs. Meanwhile, active contrast extravasation from the rectal branches was detected in the left hypogastric arteriogram. The distal internal pudendal arteriogram affirmed a suspicious distal flow with possible anastomosis to middle rectal branches. Hence, the patient underwent coil embolization of possible middle and inferior rectal collaterals of the internal pudendal artery. A prostatic arteriogram confirmed the existence of contrast extravasation from the middle rectal artery; hence, gel-foam slurry and coil embolization were applied (Fig. 1 ). The embolization procedure effectively controlled the bleeding episode. After 5 days, the patient was extubated, transferred back to the medicine floor, and later discharged to a skilled nursing facility.
Discussion
Our case report confirms that GI bleeding can adversely impact the (Table 1 ) course and outcomes of hospitalization in patients with COVID-19. COVID-19 is a predominant factor attributing to the development of DIC and GI bleeding.
Table 1
Admission vs. event laboratory results.
| Admission | Event | |
|---|---|---|
| D-Dimer | 2.3 mcg FEU/mL | >20.00 mcg FEU/mL |
| Platelet Count | 262 thou/mcL | 93 thou/mcL |
| WBC | 8.10 thou/mcL | 22.2 thou/mcL |
| Hemoglobin | 14.7 g/dL | 8.9 g/dL |
| Hematocrit | 41.7% | 41.3% |
| PT | 13.7 s | 24.7 s |
| INR | 1.1 | 2.3 |
| Fibrinogen level | 615 mg/dL | 198 mg/dL |
Clinical investigation on the mechanism of COVID-19-related lung injury continues [11], [12]. Currently, the impact of COVID-19 on the structure and function of the GI tract remains poorly understood. Tian et al. (2020) identified several GI manifestations of COVID-19 in 2023 patients. GI symptoms ranging from nausea to severe GI bleeding were found in 79% of these patients. Real-time PCR from fecal samples was more effective in detecting SARS-CoV-2 than RT-PCR. The diagnostic assessment further revealed nucleocapsid protein and angiotensin-converting enzyme-2 in the GI epithelium of a patient with COVID-19 [13]. Yang et al. (2020) reported GI bleeding in 4% of patients with COVID-19 in Wuhan Jinyintan Hospital. They further confirmed that GI bleeding is associated with a higher mortality risk and a worse adverse prognosis [8]. Thus, these findings further hint the impact of COVID-19 on the GI tract.
The deleterious impact of COVID-19 on blood vessels may increase GI bleeding risk in patients with COVID-19. The recent reports about COVID-19 pathogenesis affirm hypercoagulability as a possible prognostic outcome of this disease [14], [15], [16]. Accordingly, many clinical studies emphasize on anticoagulant therapy to prevent and treat coagulopathy in COVID-19 scenarios [16], [17]. In another study, COVDI-19 had a deleterious impact on the structure and function of the vascular endothelium [9]. Lee (2020) further advocated that COVID-19 contributes to the development of fulminant DIC while disrupting the coagulation pathway [5]. The case-control study by Martin et al. (2020) reported a 60% prevalence of rectal tube-related rectal ulcers and an 80% prevalence of gastroduodenal ulcers in patients with COVID-19 [22]. They advocated conservative management to guide the treatment of COVID-19-related GI bleeding. Moreover, the case-control study by Trindade et al. (2020) confirmed the mortality predisposition of patients with COVID-19 with GI bleeding during hospitalization [23].
SARS-CoV-2 is a deleterious respiratory virus that discreetly disrupts the human body systems [18], [19], [20], [21]. Thus, prospective studies aim to determine the effect of COVID-19 on various organ systems. Deepening our knowledge on COVID-19 is the key to curb the progression of COVID-19 worldwide.
In conclusion, our findings support the claim that SARS-CoV-2 infection can trigger episodes of DIC and GI bleeding. Future studies should investigate the potential of COVID-19 to disrupt the structure and function of the coagulation pathways, blood vessels, and epithelial cells in the GI tract. These assessments will help identify new and comprehensive prevention and treatment approaches to improve the mortality rate and prognostic outcomes of COVID-19.Go to:
Financial disclosure
The authors declare the absence of funding for this study.Go to:
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Go to:
References
1. Li T., Lu H., Zhang W. Clinical observation and management of COVID-19 patients. Emerg Microbes Infect. 2020;9(1):687–690. [PMC free article] [PubMed] [Google Scholar]
2. Oudkerk M., Büller H.R., Kuijpers D., van Es N., Oudkerk S.F., McLoud T. Diagnosis, prevention, and treatment of thromboembolic complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology. 2020;297(1):E216–E222. [PMC free article] [PubMed] [Google Scholar]
3. Jose R.J., Manuel A. COVID-19 cytokine storm: The interplay between inflammation and coagulation. Lancet Respir Med. 2020;8(6):e46–e47. [PMC free article] [PubMed] [Google Scholar]
4. Magdi M., Rahil A. Severe immune thrombocytopenia complicated by intracerebral haemorrhage associated with coronavirus infection: A case report and literature review. Eur J Case Rep Intern Med. 2019;6(7) [PMC free article] [PubMed] [Google Scholar]
5. Lee, A. Y., COVID-19 and Coagulopathy: Frequently Asked Questions. https://www.hematology.org/covid-19/covid-19-and-coagulopathy2020, version 2.0.
6. Plummer, M. P.; Blaser, A. R.; Deane, A. M., Stress ulceration: Prevalence, pathology and association with adverse outcomes. Crit Care; 2014, 18 (2), 213-213. [PMC free article] [PubMed]
7. Ali T., Harty R.F. Stress-induced ulcer bleeding in critically ill patients. Gastroenterol Clin North Am. 2009;38(2):245–265. [PubMed] [Google Scholar]
8. Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–481. [PMC free article] [PubMed] [Google Scholar]
9. Brenda Goodman M. COVID-19 lung problems may start in blood vessels. Medscape. 2020 [Google Scholar]
10. Alboraie M., Piscoya A., Tran Q.T., Mendelsohn R.B., Butt A.S., Lenz L. “The Global Endo-COVID working group”, The global impact of COVID-19 on gastrointestinal endoscopy units: An international survey of endoscopists. Arab J Gastroenterol. 2020;21(3):156–161. [PMC free article] [PubMed] [Google Scholar]
11. Gattinoni L., Chiumello D., Rossi S. COVID-19 pneumonia: ARDS or not? Crit Care. 2020;24(1):154. [PMC free article] [PubMed] [Google Scholar]
12. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. [PMC free article] [PubMed] [Google Scholar]
13. Tian Y., Rong L., Nian W., He Y. Review article: Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020;51(9):843–851. [PMC free article] [PubMed] [Google Scholar]
14. Panigada M., Bottino N., Tagliabue P., Grasselli G., Novembrino C., Chantarangkul V. Hypercoagulability of COVID-19 patients in Intensive Care Unit: A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020;18(7):1738–1742. [PubMed] [Google Scholar]
15. Spiezia L., Boscolo A., Poletto F., Cerruti L., Tiberio I., Campello E. COVID-19-Related severe hypercoagulability in patients admitted to Intensive Care Unit for acute respiratory failure. Thromb Haemost. 2020;120(06):998–1000. [PMC free article] [PubMed] [Google Scholar]
16. Connors J.M., Levy J.H. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemost. 2020;18(7):1559–1561. [PubMed] [Google Scholar]
17. Kollias A., Kyriakoulis K.G., Dimakakos E., Poulakou G., Stergiou G.S., Syrigos K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: Emerging evidence and call for action. Br J Haematol. 2020;189(5):846–847. [PMC free article] [PubMed] [Google Scholar]
18. Ali H., Daoud A., Mohamed M.M., Salim S.A., Yessayan L., Baharani J. Survival rate in acute kidney injury superimposed COVID-19 patients: A systematic review and meta-analysis. Ren Fail. 2020;42(1):393–397. [PMC free article] [PubMed] [Google Scholar]
19. Zaim S., Chong J.H., Sankaranarayanan V., Harky A. COVID-19 and multi-organ response. Curr Probl Cardiol. 2020;45(8):100618. doi: 10.1016/j.cpcardiol.2020.100618. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
20. Wang T., Du Z., Zhu F., Cao Z., An Y., Gao Y. Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet. 2020;395(10228):e52. doi: 10.1016/S0140-6736(20)30558-4. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
21. Kassem A.M. COVID-19: Mitigation or suppression? Arab J Gastroenterol. 2020;21(1):1–2. [PMC free article] [PubMed] [Google Scholar]
22. Martin T.A., Wan D.W., Hajifathalian K., Tewani S., Shah S.L., Mehta A. Gastrointestinal bleeding in patients with coronavirus disease 2019: A matched case-control study. Am J Gastroenterol. 2020;115(10):1609–1616. doi: 10.14309/ajg.0000000000000805. [PMC free article] [PubMed] [CrossRef] [Google Scholar]2
3. Trindade A.J., Izard S., Coppa K., Hirsch J.S., Lee C., Satapathy S.K. Northwell, COVID-19_Research_Consortium. J Intern Med. 2020:1–8. doi: 10.1111/joim.13232. [PubMed] [CrossRef] [Google Scholar]