Polyphosphate: A Novel Modulator of Hemostasis and Thrombosis
Although inorganic polyphosphate is widespread in biology and plays diverse roles in many organisms, most of our knowledge of its functions comes from studies of microorganisms. In 2004, Docampo and colleagues showed that polyphosphate is a major component of the dense granules in human platelets, and furthermore that platelets secrete polyphosphate upon activation. Studies from my laboratory and others have now demonstrated that polyphosphate is a novel and potentially important modulator of the human blood clotting system. Many infectious microorganisms contain long-chain polyphosphate, which is a highly potent, pathophysiologic activator of the contact pathway of blood clotting and may help explain the role of this limb of the clotting pathway in inflammation and host responses to pathogens. Shorter-chain polyphosphate—of the size range secreted by activated platelets—has multiple downstream effects on clotting, including accelerating factor V activation, abrogating the function of tissue factor pathway inhibitor (TFPI), and enhancing fibrin clot structure. Interestingly, platelet polyphosphate also greatly accelerates the back-activation of factor XI by thrombin, which may help explain the otherwise perplexing contribution of factor XI to normal hemostasis. Polyphosphate is an interesting therapeutic and diagnostic target, including the use of polyphosphates in novel hemostatic agents, as well as the use of inhibitors of polyphosphate function as a novel approach to antithrombotic/anti-inflammatory therapy. Many more contributions of polyphosphate to hemostasis, thrombosis and inflammation are doubtless waiting to be discovered.
- © 2013 by American Heart Association, Inc.