Long COVID: Coagulopathies and Microclots

Months after recovering from the initial SARS-CoV-2 infection, many people still fight debilitating symptoms with what we call Long COVID. But what is it that allows some people to recover within a couple of weeks while others suffer from long-term symptoms for months or even years? Scientist Resia Pretorius, head of the science department at Stellenbosh University in South Africa, believes that microclots found in the blood of acute COVID and Long COVID patients may be a key to unlocking the Long COVID mystery.

Clotting Mechanisms in a Healthy Body

To better understand what microclots are and what their presence means, let’s take a closer look at how a healthy body works when it comes to clotting. When you cut your finger, a clot forms to seal the wound, creating the scab that you see. However, damage can occur to the blood vessels inside your body from a simple bump into a table. When this damage occurs, the body springs into action. Platelets immediately swarm to the area of damage, adhering to the cut edges of the vessel. In addition to platelets, clotting factors in the body cause fibrin to stick and seal the damage. The platelets and fibrin work to form a plug (or clot) that stops the bleeding until the vessel heals. But once the vessel heals, what happens to the clot?

While the damage heals, alpha (2)-antiplasmin in the body helps to maintain the clot. However, once the vessel heals, the body uses an activator to trigger plasmin in the clot to begin the breakdown process. This material works similarly to an internal self-destruct button within the clot. The relationship between plasmin and antiplasmin within the body is an essential balancing act when it comes to internal healing and clot removal.

What Can Occur in the Blood of COVID and Long COVID Patients?

The research from Pretorius shows that there is an overload of inflammatory molecules trapped inside insoluble microclots in patients with acute COVID, as well as those with Long COVID. It appears that there are hyperactivated platelets and high levels of alpha (2)-antiplasmin in the body. These levels work to not only increase the formation of clots due to inflammation but also prevent the breakdown of these microclots. As these clots build up and circulate through the body, they can block small blood vessels, such as microcapillaries. This blockage can reduce the delivery of oxygen to tissues within the body. This creates hypoxia and, without the oxygen the tissues need, debilitating symptoms can occur, such as those we see in Long COVID. In addition, these microclots can also increase the risk of stroke and heart attacks, even in young patients.

How Do We Diagnose Long COVID Microclots?

When looking for these clots, traditional tests for clotting issues, such as fibrinogen and D-dimer, often show normal results. Because these tests show elevated results due to the breakdown of clots, Long COVID patients are not showing positive as the elevated rates of alpha (2)-antiplasmin are not allowing for any clot breakdown. According to UK respiratory physician Dr. Asad Khan, one test to look for these microclots may be a simple blood oxygen test that looks at the amount of oxygen traveling in the blood. If your oxygen levels are low, you may have clots limiting oxygen transport in the blood.

Treatment for Long COVID Microclots

Treatment for these microclots focuses on the breakdown of the clots as well as addressing the hyperactivated platelets. Anticlotting therapy is a traditional treatment method for blood clots. However, this requires close monitoring in order to minimize the risk of excess bleeding. Unfortunately, these microclots can often be difficult to break down and they do not always respond to this traditional treatment.

Researchers in Germany are evaluating another treatment option that is showing success. This treatment is heparin-mediated extracorporeal LDL-cholesterol precipitation (HELP) apheresis. Currently offered by Dr. Beate Jaegar, HELP apheresis works similarly to a dialysis machine. Blood from one arm enters the machine. The machine removes the clots and then returns the blood to the other arm. While the treatment appears promising, more research is necessary before HELP apheresis becomes a mainstream treatment option.

A recent preprint from Pretorius and her team shows that a combination of antiplatelet and anticoagulant therapy for those with microclots provided significant Long COVID symptom improvement, as well as a reduction in the microclots. While research is ongoing, this treatment option is very promising.

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