Can Anti-Coagulants treat Microclots?

And alleviate Long Covid symptoms?

Over the past few weeks, as I have been talking about the microclots that seem to cause Long Covid, many people have asked whether anti-coagulants can stop the formation of microclots and treat Long Covid symptoms.

The short answer is probably not, based on the available data.

There is currently no data that shows that anti-coagulants ALONE, as a mono-therapy, prevent microclot formation, break up existing microclots, or act as an effective treatment for Covid.

The detailed picture is a little more nuanced.

And very unsatisfying.

And honestly infuriating.

There have been studies done using anti-coagulants to treat Covid. But there are several issues…

Issue #1: The studies that have been done (see below) were performed on patients with primary acute Covid infections, not Long Covid.

Issue #2: The studies that have been done didn’t specifically analyze microclots in those patients and whether the anti-coagulants broke up the microclots or stopped more from forming. These studies all used improvement or worsening of patient condition, like all-cause mortality, “freedom from organ support”, or “surrogates of disease severity”, as the measured outcome.

Issue #3: When anti-coagulants were tested in these studies, the results were underwhelming:

• In one clinical trial of 615 patients (Ref 1), use of “therapeutic anti-coagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anti-coagulation” (enoxaparin or unfractionated heparin). [Basically, using it didn’t help…]

• In a second clinical trial of 2219 patients (Ref 2), “an initial strategy of therapeutic-dose anti-coagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.” [Basically, you lived long enough without life support to leave the hospital…]

Here’s the analysis from a Commentary in The Lancet from 2022 (Ref 3):

"For the most part, randomised trials to date have not shown benefits of add-on or escalated anti-thrombotic therapy over usual standard of care. Published or preprint trials of escalated or treatment dose anti-coagulants have not met their primary efficacy outcome in patients who are moderately or critically ill and hospitalised with COVID-19..." 
- Lancet 2022, 399, 118. (Ref 3)

So, in short, the studies performed to date:

• Didn’t use the Long Covid patient population

• Had no assessment of a molecular level outcomes (on microclots)

• Showed anti-coagulants didn’t help much in the measured outcome

That is the unsatisfying part.

Now, what most people will ask next is:

WHY HASN’T SOMEONE RUN THE RIGHT STUDY?

With Long Covid patients.

That examines microclots before and after anti-coagulant treatment.

To see if they work?!?!?!?!

That’s the infuriating part.

It appears that despite the strong, published evidence that microclots occur in Long Covid, and the entirely reasonable (even likely) hypothesis that microclots cause many/most of the symptoms of Long Covid, NO ONE has tested anti-coagulants as a mono-therapy to treat Long Covid.

The real answer is that we don’t know if anti-coagulants alone work to treat Long Covid.

And NO ONE seems to want to find out.

It’s mind-boggling. Especially with all the money dumped into Covid research and clinical trials over the past three years.

Putting aside the suboptimal trial designs and the lack of data related specifically to Long Covid, there is a logical and useful next question to ask:

Why did the anti-coagulant therapies fail to show improvements in acute Covid patients?

The answer: platelet hyperactivation.

In my next post I’ll describe platelet hyperactivation and how it contributes to microclots that drive symptoms in Covid and Long Covid. Stay tuned!

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References:

1. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 2021, 397, 2253-2263.

2. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N. Engl. J. Med. 2021, 385, 790-802.

3. Studying the coagulopathy of COVID-19. Lancet 2022, 399, 118-119.