A cycle of blood clotting and inflammation may contribute to the breathing difficulties of some COVID-19 patients. A forthcoming clinical trial will assess whether a type of drug already approved for the prevention of blood clots after a heart attack or stroke might help prevent these difficulties.
Critically ill patients can develop a severe inflammatory lung condition called acute respiratory distress syndrome (ARDS), which affects their ability to breathe unaided.
The hallmark of ARDS is damage to the lining of the lungs from inflammation that allows fluid to build up in the lungs. This inflammation activates increased coagulation within the small vessels of the lungs.
As part of this blood clotting-inflammation cycle, the uncontrolled development of microclots in the small blood vessels of the lungs and the microfibrin plugs in the small air sacs of some COVID-19 patients contribute to severe breathing difficulties.
Apart from supportive care and mechanical ventilation in an intensive care unit, there is currently no effective treatment.
The American Hospital Association’s “best guess” of the worst case scenario is that 1% of people in the United States who develop COVID-19, the disease that the novel coronavirus causes, could require mechanical ventilation in hospital as a result of ARDS.
Their predictions also suggest that 96 million people in the U.S. will eventually get COVID-19. Should this occur, it would mean that a total of 960,000 people would need mechanical ventilation.
The Society of Critical Care Medicine estimate that there are only about 200,000 ventilators in the U.S.
A team at Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA, has suggested that giving a widely available anticoagulant to some of these patients may not only help save their lives but also reduce the time that they need to be on a ventilator.
If successful, this would free up the machines more quickly for other COVID-19 patients who need them.
Medical News Today have previously published an article about this potential use of the drug, but now, researchers have announced that the clinical trial testing its benefits is underway.
In 1996, the Food and Drug Administration (FDA) approved the drug, which is called tissue plasminogen activator (tPA), to prevent blood clots in people who have had a stroke, pulmonary embolism, or heart attack.
It is an enzyme that occurs naturally in blood and tissues, where it acts as an anticoagulant by breaking down fibrin — which forms plugs in the airways and fibrin-platelet clots in the small vessels of the lungs.
The researchers have begun enrolling some of the COVID-19 patients admitted to the medical center into a clinical trial of the drug. They also aim to identify “biomarkers,” such as blood levels of clotting factors, that will, in the future, help identify patients who are most likely to benefit from the therapy.
“If effective and safe for the treatment of ARDS in patients with COVID-19, tPA could save lives by reducing recovery time and freeing up more ventilators for other patients in need,” says clinical trial investigator Christopher D. Barrett.
In an article in The Journal of Trauma and Acute Care Surgery, the doctors note that characteristic fibrous deposits and tiny blood clots called “microthrombi” are often present in the lungs of patients with ARDS.
These multiple tiny clots in the lungs’ blood vessels reduce the ability of these organs to get oxygen into the bloodstream and remove carbon dioxide from it.
Pathologists have found signs of what the researchers call “aggressive clotting” in lung samples from people with COVID-19. There have also been reports from intensive care units of abnormal clotting outside the lungs in COVID-19 patients with ARDS.
“We’re hearing anecdotally that a subset of patients with COVID-19-induced ARDS are clotting abnormally around their catheters and [intravenous] lines,” says senior author Dr. Michael B. Yaffe, Ph.D., an acute care surgeon at the medical center.
“We suspect these patients with aggressive clotting will show the most benefit from tPA treatment, and this new clinical trial will reveal whether that’s the case.”
– Dr. Michael B. Yaffe, Ph.D.
Several studies in animal models of ARDS have found that tPA reduces mortality, though none of them have involved a viral infection.
A clinical trial that The American Surgeon published in 2001 found that two older kinds of plasminogen activator reduced the mortality rate of patients with ARDS on ventilators.
Importantly, the drugs did not cause dangerous bleeding, which is an inherent risk of all anticoagulant treatments.
The organizers of the forthcoming clinical trial say that tPA is better at breaking up clots than the older plasminogen activators, without any increase in bleeding risk.
Furthermore, tPA has some anti-inflammatory activity, whereas older anticoagulant drugs, such as streptokinase (Streptase), promote inflammation.
“As the global pandemic of COVID-19 begins to oversaturate the world’s medical capacity to accommodate a surge of patients with ARDS, it’s critical we consider how existing therapies that are widely available may be of use in this unprecedented public health emergency.”
– Christopher D. Barrett, MD, senior surgical resident, BIDMC
In their article, the clinicians conclude, “Extraordinary times may call for extraordinary measures.”
They write that if tPA proves effective and safe in this new application, it would be straightforward for intensive care units around the world to begin using it.
Clinicians are already familiar with the drug, which is relatively inexpensive and widely available.
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