Argiro R.

Buonomo O. C.

Granai A. V.

Legramante J. M.

Morosetti D.

Vidali S.

English

Archivio della Ricerca - Università della Basilicata

1680Abstract. – OBJECTIVE: Although pulmo-nary involvement represents the primary and most characteristic presentation of Sars-Cov-2 infection, due to its innate tropism for endothelium, it is also associated with system-ic pro-coagulative changes and thromboses. This paper describes a COVID-19 atypical pre-sentation with massive thrombotic occlusion of the splenoportal-mesenteric axis and the splenic artery in the absence of clinical or ra-diological manifestation of pulmonary involve-ment.PATIENTS AND METHODS: Female patient, with no history of disease, trauma or fever in the last 30 days, was admitted to ER for per-sistent left subcostal pain. Laboratory exams, including inflammation, coagulation mark-ers and Sars-CoV-2 serology, were requested. Whole-body CT with contrast media injection was performed.RESULTS: Laboratory exams showed ele-vated reactive C-protein, bilirubin, γ-GT and D-dimer. Whole-body CT showed: splenic ar-tery occlusion, thrombosis of splenic, mesen-teric and portal veins with portal intra-hepatic branches ectasia, juxta-hilar portal caverno-matosis of probable acute onset (absence of signs of chronic hepatopathy and of varices), a hypodense area in the spleen indicating isch-emic parenchymal suffering. The patient re-sulted positive for Sars-CoV-2 IgG, thus in the absence of typical clinics or pulmonary paren-chymal abnormality at chest CT. CONCLUSIONS: A case of acute venous throm-bosis and arterial occlusion as primary manifes-tations of COVID-19.Key Words:COVID-19, Hypercoagulability, Thrombosis. IntroductionCOVID-19 disease rapidly spread around the world and in March 2020, WHO declared the pan-demic state1,2.The virus is transmitted through respiratory droplets and enters target-cells through the Angio-tensin-Converting Enzyme-2 (ACE-2), receptor particularly expressed in lung and in endothelium. The incubation lasts for 2-14 days, after which the symptomatic phase may appear with fever, cough-ing and short breath as most common presentations3.Disease assessment and monitoring is mostly performed with chest CT that shows bilateral pul-monary abnormalities in ≥75% of cases. However, diagnosis is obtained with serological testing of Sars-Cov-2 DNA and of specific IgM and IgG3,4.Although pulmonary involvement represents the primary and most characteristic presentation of the disease, Sars-Cov-2, due to its innate tropism for endo-thelial cells, demonstrated to cause systemic pro-coag-ulative changes and thrombotic events, as shown by the intense elevation of thrombosis markers such as D-di-mer observed in patients with severe disease3. This paper describes a case of COVID-19 atyp-ical presentation with thrombotic occlusion of the splenoportal-mesenteric axis and acute occlusion of the splenic artery, in the absence of clinical and radiological signs of pulmonary disease.Patients and MethodsA female patient in her 70s was admitted to ER for a 7-days intense left subcostal pain par-European Review for Medical and Pharmacological Sciences 2021; 25: 1680-1683S. VIDALI1, D. MOROSETTI1, A.V. GRANAI2, J.M. LEGRAMANTE3,  O.C. BUONOMO2, R. ARGIRÒ11Interventional Radiology Unit, Department of Biomedicine and Prevention, University Hospital Policlinico Tor Vergata, Rome Italy2UOSD Breast Unit, University Hospital Policlinico Tor Vergata, Rome, Italy3Dipartimento Medicina dei Sistemi, University Hospital Policlinico Tor Vergata, Rome, ItalyCorresponding Author: Renato Agirò, MD; e-mail: renato.argiro@gmail.comSplenoportal-mesenteric axis thrombosis and splenic artery occlusion as initial presentations of COVID-19 diseaseAbdominal vascular thrombosis in Covid-191681tially responding to oral paracetamol but rapidly recurrent, associated to absence of bowel move-ments for 8 days. The patient denied any history of fever in the past 30 days, no recent trauma, no gastro-intestinal or genital-urinary symptom and had no relevant pathological or surgical record. Vital parameters and glycemia were recorded. Clinical exam was obtained. Laboratory exams (haemachrome, cholangial-hepatic, coagulation and inflammation assets) were requested, and a blood gas analysis performed. A total body CT with contrast agent injection was then performed. Based on the CT findings, the patient received an echocardiogram, an upper and lower limbs ve-nous ultrasonography (US), Jak2/BCR/ABL dos-ing, thrombophilia screening (folic acid, B12 vita-min, LAC, Von Leiden polymorphisms, Factor II, coagulation C and S protein, APC resistance stud-ies). She additionally received Sars-Cov-2 infec-tion screening with two rhino-pharyngeal testing and 2019-n-COV IgM and IgG dosing, performed twice with chemo-luminescence technique.ResultsVital parameters showed temperature of 36.5°C, blood pressure 140/95 mmHg, cardiac frequen-cy 80 bpm, oxygen saturation in ambient air of 99% and glycaemia of 106 mg/dL. Clinical exam showed tender abdomen with diffused pain at pal-pation, mostly elicited in the left superior-external quadrant. Laboratory exams showed neutrophilia (13.6 x 103/mmc), elevated reactive C Protein (10.8 mg/dL), hyperbilirubinemia (total 1.9 mg/dL, con-jugated 0.71 mg/dL), hyper-alanine aminotrans-ferase (ALT 39 U/L, AST 55 U/L), elevated γ-GT (52 U/L), alkaline phosphatase 176 U/L, lactic de-hydrogenase 248 U/L, PT % 59, INR 1.30, APTT 43.40 sec, APTT ratio 1.40, fibrinogen 1307.00 mg/dL, D-dimer 4926.00 ng/mL. Blood gas anal-ysis showed pH 7.52, PaCO2 30 mmHg, PaO2 99 mmHg, Hb and electrolytes in NR, HCO3 25.2 mmol/L and Lactates 0.8 mmol/L.CT major findings:  - Complete occlusion of the splenic artery at its emergent from the tripod (Figure 1A).  - A non-homogeneously 3 cm hypodense area of parenchyma with non-homogeneous con-trast enhancement localised at the inferior pole of the spleen, of probable ischemic aeti-ology (Figure 1B).  - Thrombosis of the extrahepatic and intrahepat-ic portal branches extending to the splenic and superior/inferior mesenteric veins (with paten-cy of intestinal perivisceral venous branches), these associated with portal juxta-hilar cav-ernomatosis of probable acute origin. No di-rect or indirect signs of chronic hepatopathy or gastro-esophageal varices (Figure 1C).  - No direct or indirect signs of intestinal isch-emic sufferance, no intra-abdominal fluids (Figure 1D).  - No pulmonary parenchymal alterations (Fig-ure 1E).US exam was negative for deep venous throm-bosis, Jak2/BCR/ABL dosing, thrombophilia screening resulted all negative. Sars-Cov-2 infec-tion rhino-pharyngeal testing resulted negative, however, IgG dosing, resulted positive.The echocardiogram showed no evidence of in-tra-cardiac thrombi, valve or muscle disfunction, no shunts and normal dimensions of all chambers.Based on the absence of signs of sufferance of the intestinal wall and of the liver and considering the limited extension of the ischemic alteration in the spleen, surgical and interventional radiology treatments were not indicated. The patient was admitted to the general surgery department where a therapeutic scheme with 8000 UI/die of low mo-lecular heparin (LMWH).DiscussionThe injury of the endothelium and the venous stasis represent two determining triggers for thrombus formation5. Similarly, systemic inflam-mation, induce the activation of pro-coagulative states, activate endothelial cells and predispose to thrombosis6.SARS-Cov-2 infection not only induces the above-mentioned mechanisms but also, due to its innate tropism for endothelial cells, directly dam-ages them and activates intravascular coagulation, predisposing to systemic thrombotic alterations3,7.Portal thrombosis with cavernomatosis most frequently develops secondary to chronic hepa-topathies due to the congestion or compression of the intra-hepatic portal branches induced by that may induce thrombosis of the splenoportal axis and the development of anomalous and serpigi-nous accessory drainage routs8. Thus, the pre-sented patient had no clinical or radiological sign of chronic hepatopathy and/or cardiac-induced hepatopathy.COVID-19 most frequently presents with upper airways and pulmonary symptoms but the patho-S. Vidali, D. Morosetti, A.V. Granai, J.M. Legramante, O.C. Buonomo, R. Argirò1682logical involvement of different organs, especial-ly the vascular one, are described9. Although less frequent, disease presentation with severe respi-ratory and vascular abdominal alterations is de-scribed in the literature10,11. In these case reports vascular thrombotic pathologies occurred in pa-tients already hospitalised for severe COVID-19.Thrombotic manifestations in the absence of either clinical or radiological sign of pulmonary involve-ment, as described in our case, are a very uncommon clinical presentation. The patient was admitted to our ER department without any referred respiratory symptoms or fever in the previous 30 days. These dif-ferent clinical presentations could have warded off a prompt diagnosis of COVID-19, exposing healthcare providers to a high infection risk. Based on the increasing and consisting evi-dence on Sars-Cov-2, endothelial tropism and correlation of the infection with systemic throm-botic events, together with the absence of ev-idence of hepatopathy, it could be hypothesised that the thrombosis of the spleno-portomesenteric axis with cavernous transformation of the portal vein observed in the patient is a manifestation of COVID-19 disease.Concerning the thrombosis of the splenic ar-tery, a pro-thrombotic activity of Sars-CoV-2 on arterial systems has been described11. Moreover, all potential causes of arterial thromboembolism had been excluded and also, splenic artery throm-bosis is an uncommon site of thromboembolism and its embolic aetiology can be considered im-probable: therefore, we can speculate the arterial occlusion to be linked to COVID-19 disease.ConclusionsTo conclude, in case of thrombotic venous and arterial disease in patients with no detectable pre-disposing factor, it is important to evaluate the possibility of Sars-CoV-2 infection and serolog-ically exclude it, in order to safeguard caregivers and correctly address treatment plans.Figure 1. Female, 70s, intense left subcostal pain. Complete occlusion of the splenic artery at its emergent from the tripod (A). A non-homogeneously 3 cm hypodense area of parenchyma with equally non-homogeneous contrast enhancement localised at the inferior pole of the spleen, of probable ischemic aetiology (B). Thrombosis of the extrahepatic and intrahepatic portal branches associated with portal juxta-hilar cavernomatosis no direct or indirect signs of chronic hepatopathy, intestinal isch-emic sufferance and intra-abdominal fluids (C). Thrombosis of the extrahepatic and intrahepatic portal branches associated with portal juxta-hilar cavernomatosis (white circle); thrombosis extending to the splenic (arrow) and to superior/inferior mes-enteric veins with patency of intestinal perivisceral venous branches (black circle); no direct or indirect signs of chronic hepa-topathy, intestinal ischemic sufferance and intra-abdominal fluids (D). No pulmonary parenchymal alterations detectable (E).Abdominal vascular thrombosis in Covid-191683Conflict of InterestThe Authors declare that they have no conflict of interests.References 1) Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506. 2) Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L, Shan H, Lei C, Hui D S C, Du B, Li L, Zeng G, Yuen K-Y, Chen R, Tang C, Wang T, Chen P, Xiang J, Li S, Wang J, Liang Z, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Zhong N. Clinical charac-teristics of Coronavirus disease 2019 in China. N Engl J Med 2020; 382: 1708-1720. 3) Vidali S, Morosetti D, Cossu E, Luisi M L E, Pancani S, Semeraro V, Consales G. D-dimer as an indicator of prognosis in SARS-CoV-2 infection: a systematic review. ERJ Open Res 2020. 6; 00260-2020. 4) Madjid M, Safavi-Naeini P, Solomon S D, Varde-ny O. Potential effects of Coronaviruses on the cardiovascular system: a review. JAMA Cardiol 2020; 5:831-840. 5) Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res 2019; 181: 77-83. 6) Kumar DR, Hanlin E, Glurich I, Mazza JJ, Yale SH. Virchow’s contribution to the understand-ing of thrombosis and cellular biology. Clin Med Res 2010; 8: 168-172. 7) Liu PP, Blet A, Smyth D, Li H. The science un-derlying COVID-19: implications for the cardio-vascular system. Circulation 2020; 142: 68-78. 8) Intagliata NM, Caldwell SH, Tripodi A. Diagno-sis, development, and treatment of portal vein thrombosis in patients with and without cirrho-sis. Gastroenterology 2019; 156: 1582-1599. 9) Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian CD, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quéré I, Dimakakos E P, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Bur-ton JR, Francese DP, Wang EY, Falanga A, Mc-Lintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Mon-real M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH. COVID-19 and thrombotic or throm-boembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol 2020; 75: 2950-2973.10) de Barry O, Mekki A, Diffre C, Seror M, Hajjam ME, Carlier R-Y. Arterial and venous abdomi-nal thrombosis in a 79-year-old woman with COVID-19 pneumonia. Radiol Case Rep 2020; 15: 1054-1057.11) Beccara L, Pacioni C, Ponton S, Francavilla S, Cuzzoli A. 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Splenoportal-mesenteric axis thrombosis and splenic artery occlusion as initial presentations of COVID-19 disease

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Splenoportal-mesenteric axis thrombosis and splenic artery occlusion as initial presentations of COVID-19 disease

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