Pulmonary Artery Embolism in COVID-19 Despite Thrombosis Prophylaxis

Abstract

A previously healthy 39-year-old man was admitted for treatment of COVID-19 six days after the onset of symptoms. Imaging revealed bilateral extended, patchy confluent infiltrates. On oxygen 4 L/min the saturation was consistently >90%. Six days later the patient was no longer febrile, and after a further four days his oxygenation was satisfactory breathing ambient air. Two follow-up swabs at this time were negative for SARS-CoV-2. Enoxaparin 4000 IU s.c. was given daily to prevent thrombosis. One day before planned discharge, the patient reported the sudden onset of severe breathing-related pain. The D-dimer level was elevated (5.0 mg/L; normal value <0.5 mg/L). Thoracic CT a day later showed pulmonary artery embolism in both lungs with multiple bilateral filling defects in the pulmonary arteries of the lower lobes and wedge-shaped infiltrates in the dorsobasal segments of the lower lobes (a). There were also bilateral peripheral ground-glass infiltrates compatible with COVID-19 (b). The infarct pneumonia was treated with antibiotics, and oxygen 2 L/min had to be given for two days. Deep vein thrombosis in the legs or pelvis was ruled out by duplex sonography. The patient was discharged in stable condition on oral anticoagulants.

SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung

“…These changes include reductions in transcripts for proteins known to be expressed in normal pulmonary tissue (thrombomodulin, EPCR, uPA, uPAR) that would compromise the functions of anticoagulant and fibrinolytic pathways. In concert with enhanced production of bradykinin and vascular permeability, these changes are likely to create an environment in which plasma proteins are exposed to the extravascular space, resulting in increased fibrin production and reduced fibrin degradation, enabling the fibrin deposits in pulmonary vessels and alveolar spaces observed in autopsies of COVID-19 patients ( Dolhnikoff et al, 2020 ; Fox et al, 2020 ; Geerdes-Fenge et al, 2020 ; Lax et al, 2020 ), and contributing to the virulence of the virus.…”

“…The time course for the development of severe disease is typically 8–12 days, but some patients rapidly deteriorate about 7 days following development of symptoms. Lung tissue from people who died from COVID-19 has pauci-inflammatory septal capillary injury and luminal and mural fibrin deposition in alveolar septal capillaries ( Lax et al, 2020 ; Magro et al, 2020 ), thrombi in small- and medium-sized arteries ( Lax et al, 2020 ; Magro et al, 2020 ), and fibrinous thrombi in small pulmonary arterioles with evidence of tumefaction of the endothelium ( Dolhnikoff et al, 2020 ; Fox et al, 2020 ; Geerdes-Fenge et al, 2020 ; Lax et al, 2020 ). A report that administering tissue plasminogen activator (tPA) to dissolve fibrin transiently alleviates respiratory distress in COVID-19 patients supports the premise that fibrin deposition contributes to the respiratory failure ( Wang et al, 2020 ).…”

COVID-19: Epidemiologische und klinische Fakten

“…Durch frühzeitige Diagnostik und Therapie von Komplikationen, wie z. B. Thrombosen und Lungenembolien, kann die Sterblichkeit weiter reduziert werden [13,24].…”

“…Der Endothelschaden dürfte zu der Hyperkoagulabilität sowie zu Thrombosen und Embolien beitragen, die bei schweren Verläufen von COVID-19 beobachtet werden [13,24,30,31]. Ebenso lassen sich dadurch Komplikationen wie das Auftreten Kawasakiähnlicher Erkrankungsbilder bei Kindern und Jugendlichen [18,43] und Vaskulitiden verschiedener Organe erklären [45].…”

“…Möglicherweise spielten hier eine kapazitative Überforderung des Gesundheitssystems sowie die Tatsache eine Rolle, dass man erst mit der Zeit die pathomechanistischen Tücken dieses neuen Virus erkannte. Die Infektion kann eine Endotheliitis und eine Hyperkoagulabilität hervorrufen und so nicht nur bei vorbestehenden Grunderkrankungen, sondern auch bei gesunden Menschen Thromboembolien und Organversagen auslösen [13,24,30,31,45].…”