Thread by @karimbrohi

Why don't trauma patients' platelets work?

Because they're attacked by histones and explode into these (never seen before) balloons (red arrows) that don't aggregate but support thrombin generation!

ncbi.nlm.nih.gov/pubmed/31405966

Good to have this fantastic work finally in print in @PNASNews after several years of hard graft by @CommsC4TS, especially @Miss_GPie and @Paulvulliamy.

@PNASNews @CommsC4TS @Miss_GPie @Paulvulliamy We went looking for why trauma patients' platelets show a global non-responsiveness to all aggregatory stimuli, but appear to increase their contribution to clot formation on ROTEM. Weird!!?!

@PNASNews @CommsC4TS @Miss_GPie @Paulvulliamy We (and by we I mean @Miss_GPie) eventually put them under an electron microscope, expecting to see they had already degranulated. Instead we found these weird ghost structures. (That's a normal platelet below right)

@PNASNews @CommsC4TS @Miss_GPie @Paulvulliamy ..and then @Paulvulliamy found was able to directly visualise them on the imagestream.

It took discussions with international platelet experts to finally understand that these were balloon platelets - never before seen circulating in any other human disease!

@PNASNews @CommsC4TS @Miss_GPie @Paulvulliamy These platelets cannot respond to aggregatory stimuli. What's worse, transfused platelets also seem to succumb to this fate.

@PNASNews @CommsC4TS @Miss_GPie @Paulvulliamy ...and perhaps even worse - @Paulvulliamy found that shed microparticles from these balloons pepper the surface of white cells. Causing them to do who knows what!? (these red cells are monocytes)

So we then went looking for what could possibly be causing this. We've shown before that histones are released as DAMPS in massive quantities in trauma patients (ncbi.nlm.nih.gov/pubmed/23220920). Histones are known to be able to punch holes in cell membranes as part of host defence...

So we wondered if they might be doing the same thing to platelets.

...and that's exactly what we found.

So. Histones, masively released in trauma patients, punch holes in platelets causing them to become unresponsive and swell into balloons.

These surfaces support clot formation. Microparticles form in the process, stick to white cells & modulate the immune system.

#whoa!