1 in 2 people may have elevated blood clotting markers
- Researchers do not yet fully understand the mechanisms underlying the symptoms of long COVID.
- A new study shows that 28% of people with long COVID have higher levels of markers associated with blood clot formation.
- Abnormal levels of these markers were associated with impaired exercise capacity, but not other long-lasting COVID symptoms.
- These findings could inform future research into treatments aimed at reducing these abnormalities associated with blood clotting in people with long COVID.
A recent study published in the journal Blood advances found elevated levels of blood clotting markers in more than one in two people (55%) with long COVID who also had abnormal exercise test results.
People with high levels of blood clotting markers were four times more likely to have persistent deficits in exercise capacity.
These results suggest that people with long COVID should be screened for impaired exercise capacity and markers associated with blood clotting. The author of the study, Dr. Nithya Prasannanresearcher at University College London Hospital, says:
“I hope people view this research as a step forward in understanding the causes of Long COVID, which will hopefully help us guide future treatment options.”
According to the World Health Organization, more than 500 million people across the world have been diagnosed with COVID-19 so far. Although estimates vary widely, a recent meta-analysis suggests that nearly a third of all people with COVID-19 may have persistent symptoms 3 months after symptom onset.
Those COVID-19 symptoms that persist for at least three months after SARS-CoV-2 infection have been collectively described as “
Despite the growing number of people with long COVID, the mechanisms underlying these persistent COVID-19 symptoms are not well understood.
Recent studies have shown that people with long COVID are more likely to develop
Acute COVID-19 is associated with an increased risk of blood clots. Consistently, people with acute COVID-19 are more likely to have elevated levels of proteins that promote blood clotting.
One of these proteins is von Willebrand factor (VWF), which helps form a clot to seal damaged blood vessels at the site of injury. Subsequently, an enzyme called ADAMTS13 cleaves the VWF protein into smaller fragments to reduce its activity and prevent clots from forming in blood vessels.
An elevation report of VWF to ADAMTS13 is associated with an increased risk of blood clots in acute COVID-19. Such a condition involving an increased risk of blood clots is called prothrombotic state.
In the present study, the authors investigated whether such a prothrombotic state was associated with the severity of long COVID symptoms, including exercise capacity.
The current study included 330 people who had persistent symptoms 3 months or more after SARS-CoV-2 infection and visited a long outpatient COVID clinic. The majority (83%) had never been hospitalized.
At the time of the visit, the researchers administered two tests to assess participants’ endurance and exercise capacity. These stress tests involved walking at a normal pace for 6 minutes and repeatedly moving from a seated to a standing position for one minute.
The researchers used an oxygen monitor to measure blood oxygen levels during the test. They also measured changes in levels of blood lactate, which is produced by the body when oxygen supply is insufficient to maintain muscle activity.
To assess the risk of blood clotting, researchers used blood samples to categorize participants into two groups based on whether their VWF/ADAMTS13 ratio was normal (less than 1.5) or abnormal (greater than or equal to 1.5 ).
Researchers found that approximately 28% of study participants had abnormal levels of VWF/ADAMTS13. The VWF/ADAMTS13 ratio was not correlated with the severity of long COVID symptoms, including headaches, fatigue, and cognitive deficits.
However, abnormal levels of VWF/ADAMTS13 were associated with impaired exercise capacity, as measured by blood oxygen and lactate levels. Nearly 20% of participants showed impaired exercise capacity and 55% of individuals in this group had elevated levels of VWF/ADAMTS13.
Elevated levels of VWF/ADAMTS13 were four times more likely in people with impaired exercise capacity than those with normal exercise test performance. Additionally, levels of VWF and the blood clotting protein Factor VIII were also higher in people with reduced exercise capacity.
Dr Artur Fedorowskiprofessor at Karolinska University Hospital in Stockholm, Sweden, spoke with DTM about the study. He w
“The higher VWF/ADAMTS13 ratio may suggest that some patients with long-term COVID have a predisposition to microclot generation, potentially impairing normal blood flow in various crucial areas such as pulmonary or cerebral circulation. Thus, in a normal state, the patient may feel normal and compensated, whereas physical or mental exertion may reveal a lack of compensatory reserve and produce characteristic symptoms.
“This hypothesis is mechanistically very attractive, but we must keep in mind that the majority of long-term COVID patients had a normal VWF/ADAMTS13 ratio. Either the abnormality detected is only one of many symptom-generating mechanisms of long COVID, or there is no causal association.
“Instead, the true long COVID mechanism may cause symptoms and an increased prothrombotic ratio in some susceptible patients,” Dr. Fedorowski added.
Addressing future directions for research, Dr Prasannan said DTM“Assessment of the VWF/ADAMTS13 ratio has become part of routine investigations performed in patients with long COVID.”
“As part of ongoing research in the Hemostasis Research Unit, a shear flow-based assay (a platform that mimics blood flow through blood vessels) is being used to assess microclot formation in patients with long COVID.”