Podoplanin-Fc burns out platelets.

polymers, ϳ 70 mer to 250 mer, are more effective in abrogating tissue factor pathway inhibitor–anticoagulant activity. In the case of fibrin clot stabilization, polyP polymers shorter than 100 mers had no influence on fibrin clot turbidity whereas Ն 250 mer support maximal turbidity increase. Interestingly, very short phosphates, particularly PPi, effectively block the polyP-mediated enhancement of clot turbidity. In most of the experiments, the authors have included polyP isolated from bacteria (mainly contain long polyP polymers) and platelets (contain short polymers, 60 mer to 100 mer), and their effects in the assays described above were consistent with their polymer length. Overall, these data support the authors' conclusion that short polyP polymers had very little ability to activate the contact pathway, but retain the ability to inhibit tissue factor pathway inhibitor–anticoagulant activity and accelerate FV activation. Based on these findings , exploring the possibility of developing short polyP polymers as pharmacologic agents to control bleeding without the unwanted side effect of systemic activation of the contact pathway is certainly worthwhile. However, developing a shorter polymer as a potent procoagulant agent to control bleeding but not to have any side effects may not be as simple or straightforward. There is some overlap between shorter polyP polymers and longer polyP polymers in their procoagulant activity. Although this overlap may appear insignificant at face value, it still could pose a real problem in developing polyP as a valuable hemostatic agent. For example, even though the shorter polymers were 1000 times less effective than long polyP polymers in activating the contact pathway of blood coagulation, they are still 5-fold more potent than kaolin, an effective trigger of the contact pathway. This explains why polyP secreted from platelets, whose size ranges from 60 mer to 100 mer, exerts both procoagulant and proinflammatory activity in vivo. 5 Although very short polyP polymers (Ͻ 50 mer) do not activate the contact pathway, they unfortunately fail to accelerate FV activation. Despite such limitations, it is important to conduct further studies, particularly in animal model systems, to investigate whether a polyP preparation could control bleeding without causing unwanted inflammation. For this to happen, in addition to formulating a precisely sized polyP polymer , precise dosage may have to be determined. Success in exploiting the differential effects of differing length polyP polymers on blood clotting to develop a novel procoagulant agent would be a great boon to a vast number …