Mount Sinai Study Indicates COVID-19 May be Driven by Pulmonary Thrombi & Pulmonary Endothelial Dysfunction

Apr 18, 2020 | COVID-19, Endothelial Dysfunction, Icahn School of Medicine, Mount Sinai, Thrombolysis, Thrombosis

Mount Sinai Study Indicates COVID-19 May be Driven by Pulmonary Thrombi & Pulmonary Endothelial Dysfunction

Physicians/Investigators from the Icahn School of Medicine at Mount Sinai suspect that lung-based blood clots may play a role in severe cases of COVID-19. This potentially implies that a treatment course for COVID-19-based respiratory failure may center on a treatment associated with the stroke: anticoagulation drugs for milder cases and thrombolysis, or clot removal with continued anticoagulation for more severe disease.

TrialSite News summarizes this potentially important finding for the audience.

What led the researchers to consider this hypothesis?

Well, the Icahn School of Medicine team discovered that critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities—this is a condition not consistent with classical acute respiratory distress syndrome (ARDS). However, it is consistent with pulmonary vascular disease.

What were the observations leading up to this conclusion?

Previous autopsies of SARS cases (the first coronavirus) demonstrated pulmonary thrombi, pulmonary infarcts, and microthrombi in other organs.

What are pulmonary thrombi?

These are blood clots in the lungs that can cause pulmonary infarcts—the death of the lung tissue due to lack of blood supply.

How does these SARS studies relate to SARS-CoV-2 data observations?

Well, the studies of SARS-CoV-2 (present novel coronavirus) evidence similar pathophysiological derangements. Although microthrombi—that is clots in small blood vessels—are present in sepsis and classical forms of ARDS—they are not the principal drivers of respiratory failure and organ dysfunction in those cases. The Mount Sinai team suggests that in COVID-19 pneumonia, the thrombi may play a direct and important part in gas exchange abnormalities and in multisystem organ dysfunction.

The Study

The Mount Sinai team observed five cases of COVID-19 patients in Mount Sinai Health System hospitals with refractory respiratory failure requiring mechanical ventilation and shock. They report that significant pulmonary microthrombi and/or macro thromboses are suspect to acting as drivers of this pre-terminal state. When the physicians administered tPA, a thrombolytic agent used to dissolve blood clots, the cases showed rapid improvement in alveolar ventilation, oxygenation, and/or shock.

In addition to respiratory failure signs associated with their COVID-19 course, the researchers also observed evidence of “pulmonary vascular” phenotype, such as elevated protein fragments that form when a blood clot dissolves in the body and increased dead space, or air that is inhaled but doesn’t participate in the gas exchange.

Recommendation

Based on these findings, Mount Sinai investigators suggest it may be prudent to consider full systemic anticoagulation—that is, medication used to prevent the formation of blood clots—to mitigate disease progression in early stages and thrombolysis, in which clots are dissolved using thrombolytic agents, such as tPA in more serious cases.

Observation

The high prevalence of obesity, hypertension, and diabetes in patients with severe COVID-19 pneumonia may point to an underlying susceptibility to endothelial injury and dysregulation, in which the inner lining of the small arteries fails to perform all of its important functions. The researchers advise that these therapeutic approaches should be considered in the management of COVID-19 patients and must be further examined in clinical research studies.

Comment

Hooman Poor, MD, Assistant Professor of Medicine reported, “it seems that for at least the significant subset of these patients, the underlying driver of respiratory failure and organ dysfunction is actually thrombosis and endothelial dysfunction.”

Lead Research/Investigator

Hooman Poor, MD, Assistant Professor of Medicine

Call to Action: The investigators suggest clinical trials should be designed to assess the role of anticoagulation for milder disease and thrombolysis for intensified, severe disease.

Source: Mount Sinai

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