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.