Fatal Mesenteric Ischemia in a Severely Ill COVID-19 Patient: a Case Report

Case Report

Austin Crit Care Case Rep. 2021; 5(2): 1025.

Fatal Mesenteric Ischemia in a Severely Ill COVID-19 Patient: a Case Report

Wicky PH1*, Faille D2, De Chaisemartin L3,4, Nicaise Roland P4,7, Granger V3,4, Zhoury I5, Patrier J1, Pote N5, De Montmollin E1,6, Sonneville R1,7, Ajzenberg N2, Timsit JF1,6

1Medical and Infectious Diseases ICU (MI2), Bichat-Claude Bernard Hospital, France

2University of Paris, Bichat-Claude Bernard Hospital, France

3University of Paris-Saclay, INSERM UMR996, France

4Bichat-Claude Bernard Hospital, Autoimmunity and Hypersensitivity Immunology Laboratory, France

5Bichat-Claude Bernard Hospital, Pathological Anatomy Laboratory, France

6National Institute for Health and Medical Research (INSERM), IAME, France

7University of Paris, National Institute for Health and Medical Research (INSERM), France

*Corresponding author: Wicky PH - Medical and Infectious Diseases ICU (MI2), Bichat-Claude Bernard Hospital, AP-HP, 75018, Paris, France

Received: January 29, 2021; Accepted: March 03, 2021; Published: March 10, 2021


Background: Emerging data suggest a complex role for immuno-thrombosis in the thrombotic complications in COVID-19. We report the case of a fatal mesenteric ischemia to illustrate the mechanisms of endothelial dysfunction in the gut, and the resulting hypercoagulability.

Case Report: A 58-year-old woman was admitted in Intensive Care Unit, with initial severe acute respiratory distress syndrome due to SARS-CoV-2 pneumonia. Her respiratory status worsened, with a septic shock thirteen days after symptoms onset. The blood culture was positive with Pseudomonas aeruginosa and Candida. A rapid consecutive deterioration leading to multiorgan failure revealed colic perforation complicated with secondary peritonitis. Histopathological findings revealed small vein occlusions. Surprisingly, no SARS-CoV-2 viral particles could be detected in the bowel. We found intense endothelial dysfunction, contrasting with only mild neutrophil activation. A major increase in von Willebrand factor and resistance to fibrinolysis were the main hemostatic abnormalities.

Discussion: This case highlights that COVID-19-associated hypercoagulability can lead to early primitive thrombotic events in small vessels, and adds new evidence concerning a potential role for immuno-thrombosis. Close monitoring of endothelial dysfunction, and further consideration of new targets to prevent thrombosis by adjunctive therapies may thus appear fundamental.

Keywords: COVID-19; Mesenteric ischemia; Antiphospholipid syndrome; Endothelial activation; Hypercoagulability


aPLS: Antiphospholipid syndrome; ICU: Intensive Care Unit; CT: Computed Tomography; DIC: Disseminated Intravascular Coagulopathy; DRVVT: Dilute Russell’s Viper Venom Time; aPTT: Activated Partial Thromboplastin Time; PT: Prothrombin Time; aPL: Antiphospholipid; aβ2GPI: anti-β2glycoprotein I; PE: Anti-Phoshatidylethanolamine; PS/PT: Anti-Phosphatidylserine/ Prothrombin; PCR: Polymerase Chain Reaction; NETs: Neutrophil Extracellular Traps; MPO: Myeloperoxidase; vWF: von Willebrand Factor; ROTEM: Rotational Thromboelmastometry


Thrombosis is frequent in critically ill COVID-19 patients [1], despite anticoagulation [2]. The risk assessment should integrate inflammation and coagulation parameters, but several observations raised the role of immunological mechanisms in the pathophysiology of thrombosis, similar to those involved in the Antiphospholipid Syndrome (aPLS) although specific antibodies are inconstantly detected [3,4]. We report a case of mesenteric ischemia in a critically ill patient with COVID-19 pneumonia, to illustrate the interactions between endothelial activation and the risk of thrombosis, and how coagulation abnormalities could be interpreted to adapt and improve the management of thrombotic complications.

Case Presentation

A 58-year-old woman, with history of diabetes, hypertension and severe obesity, was hospitalized in Dakar, Senegal on June 21st. She reported fatigue, back pain and mild fever lasting for five days. On June 25th, nine days after the onset of symptoms, dyspnea worsened dramatically. She was tested positive for SARS-Cov-2, and transferred to a local Intensive Care Unit (ICU). A referral in our institution was decided on June 28th after seven days of hospitalization without improvement, requiring invasive mechanical ventilation. She then received Remdesivir on June 29th and corticosteroids according to a randomized controlled trial protocol.

At arrival in Paris, with a PaO2/FiO2 ratio decreased at 92mmHg, the management required usual cares associating sedative drugs infusion, neuromuscular blockade, adequate mechanical ventilation with low-tidal volumes, inhaled Nitric Oxide for 48 hours. We didn’t perform prone positioning. The hemodynamic status was stable without vasopressor support, the kidney and hepatic functions were preserved, and she never required inotropic support.

The patient initially presented with lymphopenia (0.63 G/L), but normal platelet count (429 G/L). The inflammatory syndrome was mild with a CRP level at 49 mg/L, and procalcitonin at 0.9 ng/mL. Initial ferritin dosage was at 530 μg/L. A systematic screening for cytokines levels was performed, and we found no proinflammatory cytokines profile: TNF-a and IL-1β were undetectable (0 pg/mL), IL-6 and IL- 10 were not increased (22 pg/mL and 8 pg/mL, respectively, data not shown). We found a prolonged activated Partial Thromboplastin Time (aPTT) at 39 seconds (ratio 1.43), a prolonged Prothrombin Time (PT) at 17.5 sec, normal FII, FV and FX, but decreased factor FVII (22%). Fibrinogen was increased at 5.58 g/L, D-dimers were initially at 3346 ng/mL and fibrin monomers negative (<7 μg/mL). Initial screening for lupus anticoagulant was positive, using the Dilute Russell’s Viper Venom Time (DRVVT). Still, no Antiphospholipid (aPL) antibodies were found: Anticardiolipin (aCL) IgG <3 UC, IgM 2 UC (<20 UC), IgA 2 UC, anti-β2glycoprotein I (aB2GPI) IgG <7 UC, IgM 2 UC, IgA <4 UC, anti-Phoshatidylethanolamine (PE) IgG 4 U/mL, IgM 3 U/mL, anti-Phosphatidylserine/ Prothrombin (PS/PT) IgG < 9 U/ml, IgM <9 U/ml. The C3 complement was in the range at 0.95 g/L (0.8-1.7) Notably, SARS-CoV-2 shedding was still important with a cycle threshold of 24 in endotracheal secretions, but no virus could be detected in the serum. The serology was found positive with presence of IgM, and IgG anti-SARS-CoV-2 at a level of 7.76 (>1.68, data not shown).

She was placed under thromboprophylaxis since the beginning of her hospitalization in Dakar, with initial intravenous infusion of unfractionated heparin prior to her transfer to Paris, where prophylactic subcutaneous injections of low molecular weight enoxaparin at the recommended dose (4000 UI bid) were then preferred [5].

On July 1st, a plugged telescoping catheter of the respiratory tract was performed, and cultures were positive for Klebsiella pneumonia, Pseudomonas aeruginosa and Enterococcus faecalis. Simultaneous Pseudomonas aeruginosa bacteremia was found. She was treated with the association ceftazidime-avibactam and amikacin, and vasopressor support. Concomitantly, candidemia was also diagnosed and antifungal echinocandin therapy was initiated. Despite appropriate treatment, hemodynamic deterioration occurred 24 hours later, leading to multiorgan failure. Rapid assessment by echocardiography excluded the participation of a decreased cardiac output. An abdominal Computed Tomography (CT) confirmed mesenteric ischemia with right colitis, and the absence of macrothrombi in mesenteric vessels (Figure 1a). As expected, all inflammation parameters increased markedly (Table 1). We observed an elevated procalcitonin at 10 ng/mL, and C-Reactive Protein (CRP) at 175 mg/L. IL-6 was increased up to 135.4 pg/mL, and ferritin 3591 μg/L. Platelet count dropped until 30 G/L, associated with hypofibrinogenemia, and increased fibrin monomers (Table 1), indicating Disseminated Intravascular Coagulation (DIC). Still, the same dose of enoxaparin was maintained. Indeed, heparin-induced thrombocytopenia was ruled out as anti-PF4 IgG were negative. Urgent laparotomy was decided on July 3rd, and a right colic perforation was found (Figure 1b). She died 12 hours later due to refractory shock.