To maintain the high number of blood platelets in mammalian blood, an exceptionally efficient process for platelet biogenesis is required. While recent in vitro experiments demonstrate blood flow as a key factor accelerating biogenesis, the biophysical mechanism behind this acceleration remains unclear. Here we use computer simulations to show how fluid flow can indeed strongly increase biogenesis. The key aspect of our work is that we introduce a physical mechanism, akin to the well-known Rayleigh–Plateau instability of a liquid jet, as the likely origin of accelerated platelet production. Our findings can lead to a more efficient design of microfluidic bioreactors for platelet production, but also explain the exceptionally strong coupling of fluid flow and platelet biogenesis in vivo.