High extracellular phosphate increases platelet polyphosphate content

Platelet-derived extracellular polyphosphate (PolyP) is a major mediator of thrombosis. PolyP is a linear chain of inorganic phosphate (P_i) and is stored in platelet dense granules. P_i enters cells from the extracellular fluid through phosphate transporters and may be stored as PolyP. Here we show that high extracellular P_i concentration in vitro increases platelet PolyP content, in a manner dependent on phosphate transporters, IP6K and V-type ATPases. The increased PolyP also enhanced PolyP-dependent coagulation in platelet-rich plasma. These data suggest a mechanistic link between hyperphosphatemia, PolyP and enhanced coagulation, which may be important in pathologies such as chronic kidney disease.