Hageman factor, platelets and polyphosphates: early history and recent connection

Platelet activation and blood coagulation are essential for hemostasis and contribute to a variety of other biological processes such as inflammation, complement activation and tissue repair. Factor (F)XII, originally called Hageman factor, plays an important role in the kallikrein-kinin system by activating prekallikrein. In the 1960s, a platelet activity that promoted FXII activation was identified but its biochemical nature remained unknown. Inorganic polyphosphates (poly P) are polymers that consist of many phosphate residues linked by phosphoanhydride bonds. These polymers exist in all living organisms. In bacteria, poly P is important for growth and survival. Recently, poly P has been identified in human platelet dense granules. Studied have shown that upon platelet activation and secretion, poly P activates FXII, indicating that it is most likely the elusive platelet FXII activator. Poly P also regulates coagulation and fibrinolysis. In this review, we focus on early studies of FXII and the identification of platelet FXII activation activity, and discuss recent findings of poly P in FXII activation and coagulation.