The linear polymer polyphosphate plays an important, but previously unsuspected, role in blood coagulation.
The linear polymer polyphosphate plays an important, but previously unsuspected, role in blood coagulation, researchers in the US have discovered.
When a blood vessel is cut or severed, blood begins clotting (coagulating) within seconds to fill the hole and prevent excess blood from escaping. Small cell fragments known as platelets immediately surround and plug the hole, in a process known as primary haemostasis; fibrin strands then form a network that strengthens the platelet plug, in a process known as secondary haemostasis. Fibrin strand production involves a cascade of chemical reactions that follow two parallel pathways: the contact activation pathway and the tissue factor pathway.
The possible role played by polyphosphate in this complex process was first mooted by Roberto Docampo of the University of Illinois at Urbana-Champaign, after he noticed that the granules contained within blood platelets looked very similar to organelles known as acidocalcisomes found in yeast and bacteria. Acidocalcisomes regulate levels of calcium and phosphate within these cellular organisms, and contain high levels of polyphosphate.
Docampo and his colleagues, including biochemist James Morrissey, conducted in vitro experiments exploring the effect of polyphosphate on blood plasma. They found that polyphosphate polymers with more than 45 monomer units stimulate blood coagulation in various ways. The polymers aid the contact activation pathway and increase the activity of certain enzymes in the tissue factor pathway. They also reduce the activity of two enzymes that act to break up blood clots.
’The net effect is accelerating the rate at which blood clots form and then prolonging how long they last,’ explained Morrissey. The researchers are now exploring the potential of using polyphosphate as a treatment for uncontrollable bleeding.
et alProc. Natl. Acad. Sci. USA (DOI: 10.1073/pnas.0507195103)