Platelet Membrane Protrusions: Roles in Hemostasis and Beyond.

Platelet membrane protrusions (PMPTs) are a remarkably diverse set of dynamic structures formed by platelets in response to shear stress. They are actively generated and play an integral role in hemostasis, potentially bridging the crosstalk between platelets and leukocytes. Unlike filopodia and lamellipodia, known for driving active cellular motility, PMPTs exhibit distinct characteristics. Some PMPTs, such as glycoprotein Ib-rich tethers and FLIPRs (FLow-Induced PRotrusions), possess pro-coagulant functions, either directly via phosphatidylserine exposure or by fragmenting into microparticles that provide a surface for coagulation activation. With the exception of tractopods, all PMPTs - including PITTs (Platelet-derived Integrin- and Tetraspanin-enriched Tethers) and FLIPRs- support leukocyte adhesion, thereby influencing immune cell recruitment and activation. This strongly indicates a role of PMPTs in the crosstalk between hemostasis and inflammation. Further evidence supporting this connection comes from observations of increased PMPT frequency in infection and certain autoimmune disorders. This review summarizes current knowledge on how PMPTs are formed, summarizes their structural characteristics, and the sparse information available regarding their biological roles and clinical significance.