Apparently, More Platelets Are Not Better Either

In an earlier post, I discussed a familiar response to negative PRP trials: the studies did not use “real” PRP. The platelet concentration was supposedly too low.

The theory is appealing. Platelets release growth factors, so more platelets should mean more healing. Of course, the concentrations of cartilage-degrading molecules may also increase—but let us conveniently skip that part. Some proponents have even suggested that PRP becomes effective only after a specific concentration threshold is reached.

There was just one problem: convincing clinical evidence for such a dose–response relationship was missing.

A new systematic review and meta-regression examined platelet concentration in PRP used during rotator cuff repair. Ten studies involving 696 patients were included. Higher platelet concentrations were not associated with better pain, function or retear rates. In fact, the observed relationship was in the opposite direction: increasing platelet concentration tended to be associated with worse, rather than better, outcomes.

The inverse association was not conclusive, but it makes the biological narrative even harder to defend. If platelet concentration is central to the proposed mechanism, more platelets should not repeatedly produce no additional benefit—or potentially less benefit.

Of course, this literature is extremely heterogeneous. PRP products are poorly standardised, treatment protocols vary, and reporting of their composition is often inadequate. One interpretation is therefore that PRP research is simply too poor to reveal a genuine dose–response relationship.

The less comfortable alternative is that there is no meaningful dose–response because PRP itself has little specific clinical effect beyond placebo and contextual effects.

Either way, the claim that negative trials merely used too few platelets is unsupported.

Once again, PRP provides an excellent biological story. But great theories must eventually survive clinical testing. So far, this one has not. The only credible way forward for the orthobiologics community is a sufficiently powered, multi-arm, placebo-controlled randomized trial directly comparing different PRP formulations and concentrations.