Polyphosphate as a general procoagulant agent.
BACKGROUND
Polyphosphate is secreted by activated platelets and we recently showed that it accelerates blood clotting, chiefly by triggering the contact pathway and promoting factor (F) V activation.


RESULTS
We now report that polyphosphate significantly shortened the clotting time of plasmas from patients with hemophilia A and B and that its procoagulant effect was additive to that of recombinant FVIIa. Polyphosphate also significantly shortened the clotting time of normal plasmas containing a variety of anticoagulant drugs, including unfractionated heparin, enoxaparin (a low molecular weight heparin), argatroban (a direct thrombin inhibitor) and rivaroxaban (a direct FXa inhibitor). Thromboelastography revealed that polyphosphate normalized the clotting dynamics of whole blood containing these anticoagulants, as indicated by changes in clot time, clot formation time, alpha angle, and maximum clot firmness. Experiments in which preformed FVa was added to plasma support the notion that polyphosphate antagonizes the anticoagulant effect of these drugs via accelerating FV activation. Polyphosphate also shortened the clotting times of plasmas from warfarin patients.


CONCLUSIONS
These results suggest that polyphosphate may have utility in reversing anticoagulation and in treating bleeding episodes in patients with hemophilia.
Smith
S A
SA
Department of Internal Medicine, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. sasmith6@uiuc.edu
Morrissey
J H
JH
D000925:Anticoagulants / Q000494:pharmacology; D001769:Blood / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects*; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D015942:Factor VIIa / Q000494:pharmacology; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D011122:Polyphosphates / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013916:Thrombelastography
D000925:Anticoagulants; D011122:Polyphosphates; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa