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Aorto-iliac/right leg arterial thrombosis necessitating limb amputation, pulmonary arterial, intracardiac, and ilio-caval venous thrombosis in a 40-year-old with COVID-19

      Highlights

      • COVID-19 related thrombosis may have various cardiovascular manifestations in the same patient.
      • Imaging has an important role in detection of COVID-19 related complications.
      • Knowledge of imaging and increased thromboembolism risk can lead to early detection and treatment.

      Abstract

      We describe a 40-year-old man with severe COVID-19 requiring mechanical ventilation who developed aorto-bi-iliac arterial, right lower extremity arterial, intracardiac, pulmonary arterial and ilio-caval venous thromboses and required right lower extremity amputation for acute limb ischemia. This unique case illustrates COVID-19-associated thrombotic complications occurring at multiple, different sites in the cardiovascular system of a single infected patient.

      Keywords

      1. Introduction

      Coronavirus disease 2019 (COVID)-19 is a global pandemic which has affected millions of people throughout the world. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19. SARS-CoV-2 virus predominately targets the respiratory system which can lead to pneumonia or acute respiratory distress syndrome although may also involve other organ systems or vessels and result in increased thromboembolic risk. COVID-19 related venous thromboembolism as well as thrombosis of the lower extremity arterial vasculature, mesenteric arterial vasculature, aorto-iliac, coronary arterial and cerebral arterial vasculature have been described.
      • Wichmann D.
      • et al.
      Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study.
      • Goldman I.A.
      • Ye K.
      • Scheinfeld M.H.
      Lower-extremity arterial thrombosis associated with COVID-19 is characterized by greater thrombus burden and increased rate of amputation and death.
      • Beccara L.A.
      • Pacioni C.
      • Ponton S.
      • Francavilla S.
      • Cuzzoli A.
      Arterial mesenteric thrombosis as a complication of SARS-CoV-2 infection.
      • Vulliamy P.
      • Jacob S.
      • Davenport R.A.
      Acute aorto-iliac and mesenteric arterial thromboses as presenting features of COVID-19.
      • Dominguez-Erquicia P.
      • Dobarro D.
      • Raposeiras-Roubin S.
      • Bastos-Fernandez G.
      • Iniguez-Romo A.
      Multivessel coronary thrombosis in a patient with COVID-19 pneumonia.
      • Hess D.C.
      • Eldahshan W.
      • Rutkowski E.
      COVID-19-related stroke.
      A few cases of thrombosis involving different vascular territories in the same patient with COVID-19 have been reported in the literature including a 79-year-old woman with portal venous/mesenteric arterial thrombus,
      • de Barry O.
      • Mekki A.
      • Diffre C.
      • Seror M.
      • Hajjam M.E.
      • Carlier R.Y.
      Arterial and venous abdominal thrombosis in a 79-year-old woman with COVID-19 pneumonia.
      a 75-year-old man with descending thoracic aortic and superior mesenteric arterial thrombus,
      • Vulliamy P.
      • Jacob S.
      • Davenport R.A.
      Acute aorto-iliac and mesenteric arterial thromboses as presenting features of COVID-19.
      and a 58-year-old man with pulmonary arterial, intracardiac and peripheral arterial thrombosis.
      • Ferguson K.
      • Quail N.
      • Kewin P.
      • Blyth K.
      COVID-19 associated with extensive pulmonary arterial, intracardiac and peripheral arterial thrombosis.
      To the best of our knowledge, we report the first case of aorto-bi-iliac arterial thrombosis with associated right lower extremity arterial thrombosis requiring limb amputation in a 40-year-old patient with COVID-19 who also developed thrombotic disease in the right ventricle, pulmonary arteries, and ilio-caval venous system.

      2. Case report

      A 40-year-old man was referred to our hospital after presenting initially at an outside medical facility with a two-week history of dyspnea, fever and dry cough. Past medical history included hypertension and diabetes mellitus type 2. At the outside medical facility, he tested positive for COVID-19, received prophylactic low molecular weight heparin and was found to have decreased right leg pulses six days after initial presentation. After initiation of therapeutic low molecular weight heparin for suspected arterial thrombosis, he was intubated for respiratory failure and transferred for further management. At time of admission, the patient was tachycardic with a heart rate in the 140 bpm range and had cold, mottled lower extremities with a pulseless right leg. Labs were notable for leukocytosis at 53.7 K/μL, elevated D-Dimer at 7.02 μg/mL, and elevated total creatine kinase at 3399 U/L. Computed tomography angiography (CTA) showed aorto-bi-iliac arterial thrombus, occlusion of the right common/proximal external iliac arteries, and lack of right lower extremity arterial perfusion beyond the right mid superficial femoral artery (Fig. 1). There was no evidence of significant pre-existing atherosclerotic disease. Right lower lobe subsegmental pulmonary arterial thromboembolism and suspected right ventricular thrombus were also present (Fig. 2). Diffuse, bilateral ground glass opacities with peripheral posterior consolidation were present in the lungs in an acute lung injury pattern which could be seen in patients with COVID-19 (Fig. 3). A clinical decision was made to amputate the right lower extremity due to evidence of irreversible acute limb ischemia on physical exam with a cold, mottled right leg having absent sensorimotor function and no detectable pulses. Bilateral iliac/femoral arterial thrombectomies and right lower extremity through the knee amputation were performed within the first 24 h of hospital admission. Mechanical ventilation was continued with administration of remdesivir, dexamethasone and empiric antibiotics. During the hospital course, the patient was dialyzed for rhabdomyolysis and remained on mechanical ventilation for hypoxemic respiratory failure. Echocardiogram agitated saline study was negative for patent foramen ovale or atrial septal defect. Labs were negative for JAK2 mutation, antiphospholipid syndrome and lipoprotein(a). Combined CTV (computed tomography venography)/CTA (computed tomography angiography) one week following admission demonstrated thrombus in the inferior vena cava/left common iliac vein (Fig. 4), similar right lower lobe subsegmental pulmonary emboli/right ventricular thrombus, and interval decreased burden of aorto-bi-iliac arterial thrombus. Revision of the right lower extremity amputation was later performed to the above-the-knee level with resection of phlegmonous changes. With continued ventilatory and parenteral support, the patient's clinical status slowly improved and he was discharged from the hospital 41 days from time of transfer.
      Fig. 1
      Fig. 1Maximum intensity projection (MIP) image of the lower limb CT angiography shows aorto-bi-iliac arterial thrombus and occlusion of the right common/proximal external iliac arteries (arrows) as well as occlusion of the right mid superficial femoral artery with lack of right lower extremity arterial perfusion distally (rectangle).
      Fig. 2
      Fig. 2Axial CT angiography of the chest. A) Multiple filling defects in the right lower lobe subsegmental pulmonary arteries (circle) consistent with pulmonary thromboembolism. B) Right ventricular mass (arrow) suspicious for intracardiac thrombus.
      Fig. 3
      Fig. 3Axial CT angiography of the chest in lung window. Diffuse bilateral ground glass pulmonary opacities with dependent consolidation and dilated airways, suggestive of diffuse alveolar damage.
      Fig. 4
      Fig. 4Axial CT venogram of the lower extremity following bilateral iliofemoral arterial thrombectomies. A) Filling defect in the infrarenal inferior vena cava representing nonocclusive thrombus. B) Occlusive thrombus in the left common iliac vein.

      3. Discussion

      Lung conditions such as pneumonia or acute respiratory distress syndrome are features of COVID-19.
      • Hu B.
      • Guo H.
      • Zhou P.
      • et al.
      Characteristics of SARS-CoV-2 and COVID-19.
      However, the coronavirus SARS-CoV-2 causing COVID-19 can result in various other forms of pathology including hypercoagulability.
      • Haimei M.A.
      Pathogenesis and treatment strategies of COVID-19-related hypercoagulant and thrombotic complications.
      Venous thromboembolism (VTE) is a commonly reported thrombotic event associated with COVID-19.
      • Abou-Ismail M.Y.
      • Diamond A.
      • Kapoor S.
      • Arafah Y.
      • Nayak L.
      The hypercoagulable state in COVID-19: incidence, pathophysiology, and management.
      A recent meta-analysis estimates the incidence of pulmonary embolism and deep venous thrombosis in COVID-19 patients to be 14% and 12% respectively.
      • Kunutsor Setor K.
      • Laukkanen Jari A.
      Incidence of venous and arterial thromboembolic complications in COVID-19: a systematic review and meta-analysis.
      In contrast, the incidence of other thrombotic events such as systemic arterial embolism, ischemic stroke and limb ischemia are lower at 2%, 2% and 1% respectively.
      • Kunutsor Setor K.
      • Laukkanen Jari A.
      Incidence of venous and arterial thromboembolic complications in COVID-19: a systematic review and meta-analysis.
      We present a rare case of thrombosis involving the aortoiliac/right lower extremity arterial vasculature resulting in acute limb ischemia requiring amputation in a patient who also developed pulmonary arterial, right ventricular and ilio-caval venous thromboses. There have been recently proposed hypotheses related to the pathophysiology underlying COVID-19 associated hypercoagulability. Release of inflammatory cytokines may activate endothelial cells, neutrophils and monocytes resulting in a prothrombotic environment.
      • Abou-Ismail M.Y.
      • Diamond A.
      • Kapoor S.
      • Arafah Y.
      • Nayak L.
      The hypercoagulable state in COVID-19: incidence, pathophysiology, and management.
      Also, direct SARS-CoV-2 viral infection of the endothelium via the ACE2 (angiotensin-converting enzyme 2) receptor is thought to ultimately induce formation of thrombin and fibrin clot.
      • Abou-Ismail M.Y.
      • Diamond A.
      • Kapoor S.
      • Arafah Y.
      • Nayak L.
      The hypercoagulable state in COVID-19: incidence, pathophysiology, and management.
      ACE2 was found in both arterial and venous endothelial cells in multiple different organs.
      • Hamming I.
      • Timens W.
      • Bulthuis M.L.
      • Lely A.T.
      • Navis G.
      • van Goor H.
      Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J.
      Published guidelines suggest that thromboprophylaxis anticoagulation be used in acutely ill hospitalized or critically ill patients with COVID-19 in the absence of contraindications.
      • Moores L.K.
      • Tritschler T.
      • Brosnahan S.
      • et al.
      Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST guideline and expert panel report.
      However, the optimal approach to management of anticoagulation in patients with COVID-19 is not certain.
      • Mondal S.
      • et al.
      Thromboembolic disease in COVID-19 patients: a brief narrative review.
      Of note, our patient had reportedly received prophylactic low molecular weight heparin at an outside medical facility prior to presentation to our hospital. The failure of thromboprophylaxis in COVID-19 patients has been described in the literature previously and may be due to multiple prothrombotic factors.
      • Kow C.S.
      • Hasan S.S.
      Use of low-molecular-weight heparin in COVID-19 patients.

      4. Conclusion

      This case highlights that thrombosis may affect different sites and types of vasculature within the same individual with COVID-19. A high index of clinical suspicion is required for potential complications related to hypercoagulability in the setting of COVID-19. Imaging has a pivotal role for diagnosis of these complications.

      Declaration of competing interest

      None.

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