title: Caveats in studies of the physiological role of polyphosphates in coagulation.
abstract: Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation.
authors: Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden tomas.lindahl@liu.se.
authors: Tomas L
authors: TL
authors: Lindahl
authors: Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
authors: Sofia
authors: S
authors: Ramström
authors: Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden Department of Haematology, Region Östergötland, SE-581 85 Linköping, Sweden.
authors: Niklas
authors: N
authors: Boknäs
authors: Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
authors: Lars
authors: L
authors: Faxälv
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D011122:Polyphosphates / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014914:Whole Blood Coagulation Time
chemical_list: D011122:Polyphosphates; D002118:Calcium
keywords: blood; coagulation; contact activation; phosphatase; platelets; polyphosphate