The study of disease-induced clotting stretches back more than a century. Writing in 1903, pathologists described the same phenomenon in typhoid fever. Adam Cunningham, an immunologist at the University of Birmingham, notes that
many common bacteria, such as Helicobacter pylori and Escherichia coli, have also been associated with an increased risk of blood clots. If this
fact has mostly been forgotten, it may be on account of our success at treating such infections. “One of the things that probably made a big difference was the introduction of the antibiotic era, so many of the pathogens didn’t get that severe,” Cunningham says.
In 2006, I wrote up a large-scale study finding that patients suffering from respiratory or urinary tract infections were at doubled risk of developing deep vein thrombosis, a potentially fatal complication of abnormal clotting. Then I, too, forgot about it. (The actual magnitude of this risk has not been pinned down.) That’s just one of many such findings, though. Other viruses associated with clotting complications include hepatitis, measles and HIV. There are similar reports in cases of H1N1, also known as swine flu: Canadian doctors looked at the records of 119 patients hospitalized during the 2009 pandemic outbreak of that disease and found that seven had experienced major clots. These occurred everywhere from the patients’ lungs to their arms.
Although there are many examples of this in the research literature, clotting still isn’t thought of as a typical outcome from viral lung infections. “It’s not the first thing you expect of a respiratory disease,” says Nonantzin Beristain Covarrubias, a research fellow and collaborator of Cunningham’s at the University of Birmingham. But that same literature reveals that blood clots have been linked to other coronaviruses. Clotting was found in the small veins of Chinese patients struck by severe acute respiratory syndrome (SARS), a coronavirus illness that hit multiple countries in 2003. In Singapore, a handful of critically ill SARS patients developed the complication in their brains, lungs and other organs. Local medical researchers called for “increased vigilance” against stroke in future SARS-CoV outbreaks.
Another life-threatening condition related to blood clots was seen in the past among both SARS patients and those infected with the coronavirus that causes Middle East respiratory syndrome (MERS). When blood clots form, they can use up the body’s available platelet cells. Since these platelets are crucial for stopping bleeding under normal circumstances, this can lead to a dangerous problem known as thrombocytopenia. As many as one-third of patients with MERS in one Saudi Arabia study developed thrombocytopenia. The same condition has also been observed in patients with Covid-19. (Low platelet counts are also linked to a scary condition in which blood clots spread throughout a person’s blood vessels, though there isn’t yet consensus on whether this risk is present in the current pandemic.)
Many different pathogens are linked to blood disorders, but the specific clotting mechanisms may vary. These details matter: If we know exactly how a particular infection leads to blood clots, we can make a better guess at which drugs might be most useful as a treatment.
It’s still completely unknown how Covid-19 causes clots. It might be doing this indirectly, by ramping up inflammation throughout the body. Or it could be infecting the lining on the insides of blood vessels. These endothelial cells regulate how much fluid can flow into each vessel, and help coordinate the clotting response after injury. The virus could end up making these cells send out their clotting signals inappropriately. Covid-19 might also be causing blood problems via the adaptive immune response, Cunningham says. He wonders whether immune cells that are specifically targeted to the Covid-19 virus in later stages of infection are involved in clotting.
...
This was known as far back as February, when doctors in Wuhan, China, reported that among 183 people hospitalized with the disease, more than two-thirds of those who died had abnormal clotting. That’s compared with less than 1 percent of those who survived.
Health workers treating Covid-19 patients have been astonished to see that patients on anticoagulants still develop clots, according to Dimitrios Giannis, a doctor and health outcomes researcher at Northwell Health’s Feinstein Institute for Medical Research in Manhasset, New York. The hospital system he is affiliated with is planning a clinical trial to see how different doses of blood thinners might be used to prevent or treat clotting in this pandemic disease, and others such studies are already underway elsewhere. But these drugs can have side effects, such as bleeding, and must be administered carefully. Meanwhile, other places are trying to bust up Covid-19-associated clots with tissue plasminogen activator, a drug normally deployed against strokes and heart attacks.
...
Giannis says that once he started looking into the phenomenon, he was surprised to find published papers on blood-clot risks associated with SARS and MERS. “We found out many similarities with previous coronaviruses—things we didn’t even know were reported previously. So, it was a good lesson to study all the literature and identify all the relevant studies.”
...
https://www.wired.com/story/covid-19s-scary-blood-clots-arent-that-surprising/
