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Review
. 2015 May;37 Suppl 1(0 1):31-5.
doi: 10.1111/ijlh.12349.

Polyphosphate, platelets, and coagulation

R J Travers  1 , S A Smith  1 , J H Morrissey  1
Affiliations
Review

Polyphosphate, platelets, and coagulation

R J Travers et al. Int J Lab Hematol. 2015 May.

Abstract

While we have understood the basic outline of the enzymes and reactions that make up the traditional blood coagulation cascade for many years, recently our appreciation of the complexity of these interactions has greatly increased. This has resulted in unofficial 'revisions' of the coagulation cascade to include new amplification pathways and connections between the standard coagulation cascade enzymes, as well as the identification of extensive connections between the immune system and the coagulation cascade. The discovery that polyphosphate is stored in platelet dense granules and is secreted during platelet activation has resulted in a recent burst of interest in the role of this ancient molecule in human biology. Here we review the increasingly complex role of platelet polyphosphate in hemostasis, thrombosis, and inflammation that has been uncovered in recent years, as well as novel therapeutics centered on modulating polyphosphate's roles in coagulation and inflammation.

Keywords: Polyphosphate; coagulation; hemostasis; platelets; thrombosis.

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Conflict of interest statement

Conflict of interest disclosure

The authors are co-inventors on patent applications on medical uses of polyphosphate and inhibitors of polyphosphate.

Figures

Figure 1
Figure 1
PolyP is a linear polymer of inorganic phosphates held together by the same type of high-energy phosphoanhydride bonds found in ATP.
Figure 2
Figure 2
PolyP modulates the blood clotting cascade by: (1) potently triggering the contact pathway of blood clotting; (2) accelerating factor V activation; (3) enhancing fibrin clot structure; and (4) greatly accelerating the rate of factor XI activation by thrombin. Reaction 1 requires long-chain polyP of the type present in microbes (hundreds of phosphates long). The other three reactions are promoted by both long-chain polyP and polyP of the size secreted by platelets (about 60–100 phosphates long), although enhancement of fibrin clot structure is most significant in the presence of long-chain polyP.
See this image and copyright information in PMC

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