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Thrombosis risk of COVID-19 — Dutch National Institute for Public Health

A special report outlines prevention, diagnosis and treatment of complications stemming from blood clots in patients with COVID-19. Two research letters and a case study on this topic were also published.

Clinicians worldwide face this new severe infectious lung disease with no proven therapies. Based on recent reports that demonstrated a strong association between elevated D-dimer levels and poor prognosis, concerns have risen about thrombotic complications in patients with COVID-19.

The National Institute for Public Health of the Netherlands asked a group of radiology and vascular medicine experts to provide guidance for the imaging workup and treatment of these important complications. Their report summarises evidence for thrombo-embolic disease and potential diagnostic and preventive actions that can be taken.

"Worldwide, COVID-19 is being treated as a primary pulmonary disease," said Dr Edwin JR van Beek, director at Edinburgh Imaging, Queens Medical Research Institute, at the University of Edinburgh. "From the analysis of all available current medical, laboratory and imaging data on COVID-19, it became clear that symptoms and diagnostic tests could not be explained by impaired pulmonary ventilation alone."

Recent observations suggest that respiratory failure in COVID-19 is not driven by the development of the acute respiratory distress syndrome alone, but that microvascular thrombotic processes may play a role. This may have important consequences for the diagnostic and therapeutic management of these patients. There is a strong association between D-dimer levels, disease progression and chest CT features suggesting venous thrombosis. In addition, various studies in patients with COVID-19 have shown a very strong association between increased D-dimer levels and severe disease/poor prognosis.

The report authors stress that careful attention needs to be paid to the initial diagnosis and treatment of the prothrombotic and thrombotic state that can occur in a substantial percentage of COVID-19 patients.

"Imaging and pathological investigations confirmed the COVID-19 syndrome is a thrombo-inflammatory process that initially affects lung perfusion, but consecutively affects all organs of the body," van Beek said. "This highly thrombotic syndrome leads to macro-thrombosis and embolism. Therefore, strict thrombosis prophylaxis, close laboratory and appropriate imaging monitoring with early anti-coagulant therapy in case of suspected venous thromboembolism are indicated."

Recommendations for diagnostic and therapeutic management, which vary based on patient symptoms and risk profiles, include prophylactic-dose heparin, chest CT, CT pulmonary angiography and routine D-dimer testing.

Findings have also emerged linking COVID-19 more specifically with pulmonary embolism. A research letter from Hôpitaux Universitaires de Strasbourg reported that of 106 pulmonary CT angiograms performed for COVID-19 patients over a one-month period in a tertiary care centre in France, 32 patients (30%) had acute pulmonary embolus (PE). This rate of PE is much higher than usually encountered in critically ill patients without COVID-19 infection (1.3%,) or in emergency department patients (3 to 10%). In the study, a D-dimer threshold of 2660 μg/L detected all patients with PE on chest CT.

A second research letter published today described a study from Centre Hospitalier Universitaire de Besancon in France pointed to high proportion (23%) of COVID-19 patients with contrast CT had PE. PE was diagnosed at mean of 12 days from symptom onset. Patients with PE were more likely require care in the critical care unit and to require mechanical ventilation.

Lastly, a case report from Cooper University Hospital in Camden, New Jersey, describes multiple areas of pulmonary and arterial thrombosis in an 84-year-old man with COVID-19.

"COVID-19 is more than a lung infection," van Beek said. "It affects the vasculature of the lungs and other organs and has a high thrombosis risk with acute life-threatening events that require adequate treatment with anticoagulants based on laboratory monitoring with appropriate imaging tests as required."

RSNA is committed to connecting radiologists and the radiology community to the most timely and useful COVID-19 information and resources. RSNA's COVID-19 Resources page (https://www.rsna.org/covid-19) houses the latest guidance, original research, image collection and more. The page will be updated on an ongoing basis.

Abstract 1
A potential link between mortality, D-dimer values and a prothrombotic syndrome has been reported in patients with COVID-19 infection. The National Institute for Public Health of the Netherlands asked a group of Radiology and Vascular Medicine experts to provide guidance for the imaging workup and treatment of these important complications. This report summarizes evidence for thromboembolic disease, potential diagnostic and preventive actions as well as recommendations for patients with COVID-19 infection
.

Authors
Matthijs Oudkerk, Harry R Büller, Dirkjan Kuijpers, Nick van Es, Sitse F Oudkerk, Theresa C McLoud, Diederik Gommers, Jaap van Dissel, Hugo ten Cate, Edwin J van Beek

Research letter authors 1
Ian Leonard-Lorant, Xavier Delabranche, François Severac, Julie Helms, Coralie Pauzet, Olivier Collange, Françis Schneider, Aissam Labani, Pascal Bilbault, Sébastien Moliere, Pierre Leyendecker, Catherine Roy, Mickaël Ohana

Research letter authors 2
Franck Grillet, Julien Behr, Paul Calame, Sébastien Aubry, Eric Delabrousse

Doctors and researchers are concerned about the increase in blood clotting among COVID-19 patients. Dr Jeffrey Laurence, a haematologist at Weill Cornell Medicine in New York City is quoted in a Science Times report as saying that the number of clotting problems on COVID-19 patients in the ICU is unprecedented. It appears to be widespread in severe coronavirus patients.

The report says that it has been a rising concern in frontline reports from the US, Europe, and China. Blood clots can cause amputation on limbs and also lethal pulmonary embolisms, heart attacks, and strokes once it reaches the lungs, heart and the brain. An international team of experts led by Dr Behnood Bikdeli from the New York-Presbyterian Hospital studied the issue. Bikdeli said that their findings showed that the risks among COVID-19 patients were so great that they "may need to receive blood thinners, preventively, prophylactically, even before imaging tests are ordered."

The reasons why blood clotting occurs are not fully understood, but Bikdeli offered several possible explanations. Patients with severe cases of COVID-19 are more likely to experience blood clotting when they have underlying medical conditions such as heart or lung disease. Another explanation, is that patients in the intensive care units are likelier to develop a clot because they are staying still for long periods.

Some research is also indicating that "cytokine storm"-an abnormal immune reaction- are linked to higher rates of clotting as it is widely associated with COVID-19.

But there could also be something in the virus itself causing the clotting. The report says a recent paper in The Lancet journal showed that the virus can infect the endothelium cells of blood vessels that could interfere with the clotting process.

Although Heparin is effective in some patients, some clots are too small that they do not work for all patients. Autopsies have shown that there are hundreds of micro clots in some people's lungs.

Military veterans hospital intensive care doctor, Cecilia Mirant-Borde said that micro clots help explain why ventilators work poorly for patients with low blood oxygen. It is the micro clotting that is blocking the circulation which leads the blood leaving the lungs with lesser oxygen than it should get.

Researchers are learning more every day since the pandemic began five months ago in Wuhan, China.

Abstract
Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Authors
Behnood Bikdeli, Mahesh V Madhavan, David Jimenez, Taylor Chuich, Isaac Dreyfus, Elissa Driggin, Caroline Der Nigoghossian, Walter Ageno, Mohammad Madjid, Yutao Guo, Liang V Tang, Yu Hu, Jay Giri, Mary Cushman, Isabelle Quéré, Evangelos P Dimakakos, C Michael Gibson, Giuseppe Lippi, Emmanuel J Favaloro, Jawed Fareed, Joseph A Caprini, Alfonso J Tafur, John R Burton, Dominic P Francese, Elizabeth Y Wang, Anna Falanga, Claire McLintock, Beverley J Hunt, Alex C Spyropoulos, Geoffrey D Barnes, John W Eikelboom, Ido Weinberg, Sam Schulman, Marc Carrier, Gregory Piazza, Joshua A Beckman, P Gabriel Steg, Gregg W Stone, Stephan Rosenkranz, Samuel Z Goldhaber, Sahil A Parikh, Manuel Monreal, Harlan M Krumholz, Stavros V Konstantinides, Jeffrey I Weitz and Gregory YH Lip

Reports of strokes in the young and middle-aged are the latest twist in our evolving understanding of COVID-19. The Washington Post reports that the numbers of those affected are small but nonetheless remarkable because they challenge how doctors understand the virus. Even as it has infected close to 3m people its biological mechanisms continue to elude top scientific minds. Once thought to be a pathogen that primarily attacks the lungs, it has turned out to be a much more formidable foe — impacting nearly every major organ system in the body.

Until recently, there was little hard data on strokes and COVID-19. But the report says, now analyses suggest coronavirus patients are mostly experiencing the deadliest type of stroke. Known as large vessel occlusions, or LVOs, they can obliterate large parts of the brain responsible for movement, speech and decision-making in one blow because they are in the main blood-supplying arteries.

Many researchers suspect strokes in VOID-19 patients may be a direct consequence of blood problems that are producing clots all over some people’s bodies. Robert Stevens, a critical care doctor at Johns Hopkins Hospital in Baltimore, called strokes “one of the most dramatic manifestations” of the blood-clotting issues. “We’ve also taken care of patients in their 30s with stroke and COVID, and this was extremely surprising,” he said.

[link url="https://www.sciencedaily.com/releases/2020/04/200423143100.htm"]Radiological Society of America material[/link]

[link url="https://pubs.rsna.org/doi/10.1148/radiol.2020201629"]Radiology abstract 1[/link]

[link url="https://pubs.rsna.org/doi/10.1148/radiol.2020201561"]Radiology research letter 1[/link]

[link url="https://pubs.rsna.org/doi/10.1148/radiol.2020201544"]Radiology research letter 2[/link]

[link url="https://pubs.rsna.org/doi/10.1148/radiol.2020201623"]Radiology images[/link]

[link url="https://www.sciencetimes.com/articles/25486/20200427/thrombotic-events-mysteriously-occur-many-covid-19-patients.htm"]Science Times material[/link]

[link url="http://www.onlinejacc.org/content/early/2020/04/15/j.jacc.2020.04.031?_ga=2.195508012.1832676774.1588141214-1333555501.1588141214"]The American College of Cardiology abstract[/link]

[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext"]The Lancet correspondence[/link]

[link url="https://www.washingtonpost.com/health/2020/04/24/strokes-coronavirus-young-patients/?utm_campaign=29345&utm_medium=email&utm_source="]Full report in The Washington Post[/link]

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