Triple Therapy for Long COVID: What It Is and What the Evidence Shows

"Triple therapy" comes up constantly in Long COVID communities, usually as a question: what is it, who prescribes it, and is the bleeding risk worth it? This guide explains the regimen, the one published dataset behind it, the strongest criticism, and the safety questions to settle with a doctor before anything else.

What is triple therapy for long COVID?

It's a combination of three drugs that act on clotting in different ways, aimed at the fibrin amyloid microclots described by Resia Pretorius, Douglas Kell and colleagues. In the published cohort, patients took:

The idea comes from a 2022 review in the Biochemical Journal. It argued that fibrinolysis-resistant microclots and hyperactivated platelets reduce blood flow in small vessels, so dampening both clotting pathways might help. If you're new to the concept, start with what microclots are.

What did the triple therapy study find?

The only dataset is a 2023 preprint from South Africa. Clinicians treated 91 Long COVID patients with the regimen above and compared symptoms and blood samples before and after. Most patients reported that symptoms such as fatigue and brain fog improved, and microclot and platelet scores on Thioflavin T microscopy fell.

That sounds encouraging, but the design can't answer whether the drugs worked:

• No control group. Long COVID symptoms often fluctuate and improve with time, so improvement after any treatment is expected in some people.
• No blinding. Patients and clinicians knew the treatment, which affects how symptoms are reported.
• Not peer reviewed as a preprint, and from the same research network that proposed the hypothesis.
• Selected patients. Treatment was started by clinicians after microclot findings, not randomly assigned.

Why do haematologists object?

In 2024 a group led by haematologist Beverley Hunt published a critique of the microclot hypothesis. They concluded the evidence didn't support thrombosis as the driver of long COVID, and that using unlicensed antithrombotic combinations outside clinical trials wasn't justified given the bleeding risk. Kell, Khan and Pretorius replied that the critique misread their data.

Science journalism has reflected the same split. Undark's reporting describes patients paying for triple therapy while researchers on both sides call for proper trials. Our summary of amyloid microclots research covers the wider debate.

Next step

Want data before you talk to a doctor about microclots?

Our at-home amyloid fibrin test records Thioflavin T microscopy of your sample. It's observational data for your clinician, not a reason to start blood thinners.

See the at-home test

What are the risks of triple therapy?

Bleeding is the main one, and it isn't theoretical. Each drug raises bleeding risk on its own, and combining an anticoagulant with two antiplatelets is normally reserved for specific heart conditions, for short periods, under close monitoring. Risks include:

• easy bruising, nosebleeds and heavy periods;
• bleeding from the stomach or bowel, which can be serious;
• rarely, bleeding in the brain.

Risk rises with age, kidney problems, stomach ulcers, low platelets and other medicines or supplements. That includes enzymes like nattokinase and lumbrokinase, covered in our nattokinase for microclots review.

Seek urgent care for black or bloody stools, vomiting blood, a sudden severe headache, or bleeding that won't stop.

Questions to ask before considering it

If a clinic suggests triple therapy, these questions protect you:

• What's the evidence, and what will we measure? Agree on symptoms or tests to track before starting, so you know whether it's working.
• How was my bleeding risk assessed? Kidney function, blood count, stomach history and every medicine and supplement should be reviewed.
• How long, and how do we stop? Open-ended treatment without review is a red flag.
• Who do I call if I bleed? You need a clear plan and access to the prescriber.
• Is there a trial I could join instead? A trial adds monitoring and helps answer the question for everyone.

Should you get a microclot test first?

Some clinics use microclot imaging to decide who to treat. A test can add information, but there's no validated cutoff that says "treat," and a result shouldn't be the sole basis for starting blood thinners. Our guide on how to test for microclots explains what each method shows. If your routine labs are normal, does long COVID show up on blood tests explains why that's common.

Where to go next

For the other treatment that comes up most, read our guide to plasmapheresis for long COVID. If you're still deciding whether microclots are part of your picture, the amyloid fibrin test guide explains what microscopy can and can't tell you.