When does PRP stop being PRP?

This question has been on my mind.

The more I read about platelet-rich plasma (PRP), the more I realise I am not entirely sure where its boundaries lie.

Fresh PRP seems easy enough to define.

Blood is drawn into a tube containing an anticoagulant. The blood is centrifuged. Platelets become concentrated within the plasma. The resulting liquid contains viable platelets suspended in plasma.

Most people would probably agree that this is PRP.

But then things start to happen.

Platelets are not static little containers of growth factors.

They are living cells.

They respond to their environment. They activate. They change shape. They release their contents. Eventually they die.

And that is where I start to get curious.

When does PRP stop being PRP?

Some clinicians deliberately activate PRP before use.

Calcium is commonly used for this purpose. The idea is to encourage platelets to release their contents before administration. Other activation methods have also been described.

Personally, I have always preferred to allow the PRP to encounter the tissue and activate naturally. After all, platelets have evolved to respond to tissue injury. When PRP is injected into the tissue we are trying to treat, it encounters collagen, inflammatory signals, tissue factor and a host of other cues that trigger activation.

That feels more physiological to me.

But perhaps there are situations where pre-activation makes sense.

I am not sure.

What interests me is what happens next.

Once platelets begin releasing their contents, are we still dealing with the same biological product?

The platelets are still there.

But they are no longer resting platelets.

Growth factors are being released.

Cytokines are being released.

Chemokines are being released.

Extracellular vesicles are being released.

The biological environment has changed.

Leave the preparation for longer and more changes occur.

More release.

More degradation.

Fewer viable platelets.

More platelet fragments.

More extracellular vesicles.

More growth factors floating freely within the plasma.

At some point I find myself wondering whether I am still looking at platelet-rich plasma at all.

Or am I looking at something else?

A growth factor-rich fluid?

A platelet-conditioned plasma?

A biological soup?

That last phrase sounds slightly ridiculous.

Yet I am not entirely convinced it is wrong.

The question became even more interesting when I recently came across a laboratory study in which PRP was stored for up to fifteen days before being used.

My immediate thought was simple.

Is that still PRP?

The preparation appeared to retain biological activity in the study. The cells in the experiment responded to it. Something biologically important remained.

But what exactly?

Viable platelets?

Released growth factors?

Extracellular vesicles?

Plasma proteins?

Some combination of all of them?

I do not know.

And perhaps that uncertainty points towards a bigger question.

Maybe before I can answer when PRP stops being PRP, I first need to answer what PRP actually is. I ponder this big question in my blog What is the therapeutic agent in PRP?

The more I read, the less PRP resembles a conventional drug.

Drugs have active ingredients.

PRP appears to have active processes.

Perhaps that is why the question is so difficult to answer.

Maybe there is no single moment when PRP stops being PRP.

Maybe there is only a gradual transition from one biological state to another.

A continuum rather than a boundary.

And perhaps the answer depends entirely on what we believe the therapeutic product actually is.

At the moment, I honestly do not know.

But I suspect this question is more important than it first appears.

Because before we can decide how to prepare PRP, how to measure PRP, how to compare PRP studies, or even how to regulate PRP, we probably need to understand what it is that we are actually talking about.

When does PRP stop being PRP?

I am still trying to work that out.