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Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates.
J Thromb Haemost. 2013 Jul; 11(7):1341-52.JT

Abstract

BACKGROUND

Inorganic polyphosphates (polyP), which are secreted by activated platelets (short-chain polyP) and accumulate in some bacteria (long-chain polyP), support the contact activation of factor XII (FXII) and accelerate the activation of FXI.

OBJECTIVES

The aim of the present study was to evaluate the role of FXI in polyP-mediated coagulation activation and experimental thrombus formation.

METHODS AND RESULTS

Pretreatment of plasma with antibodies that selectively inhibit FXI activation by activated FXII (FXIIa) or FIX) activation by activated FXI (FXIa) were not able to inhibit the procoagulant effect of long or short-chain polyP in plasma. In contrast, the FXIIa inhibitor, corn trypsin inhibitor, blocked the procoagulant effect of long and short polyP in plasma. In a purified system, long polyP significantly enhanced the rate of FXII and prekallikrein activation and the activation of FXI by thrombin but not by FXIIa. In FXI-deficient plasma, long polyP promoted clotting of plasma in an FIX-dependent manner. In a purified system, the activation of FXII and prekallikrein by long polyP promoted FIX activation and prothombin activation. In an ex vivo model of occlusive thrombus formation, inhibition of FXIIa with corn trypsin inhibitor but not of FXI with a neutralizing antibodies abolished the prothrombotic effect of long polyP.

CONCLUSIONS

We propose that long polyP promotes FXII-mediated blood coagulation bypassing FXI. Accordingly, some polyp-containing pathogens may have evolved strategies to exploit polyP-initiated FXII activation for virulence, and selective inhibition of FXII may improve the host response to pathogens.

Authors+Show Affiliations

Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA. puygarci@ohsu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23659638

Citation

Puy, C, et al. "Factor XII Promotes Blood Coagulation Independent of Factor XI in the Presence of Long-chain Polyphosphates." Journal of Thrombosis and Haemostasis : JTH, vol. 11, no. 7, 2013, pp. 1341-52.
Puy C, Tucker EI, Wong ZC, et al. Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates. J Thromb Haemost. 2013;11(7):1341-52.
Puy, C., Tucker, E. I., Wong, Z. C., Gailani, D., Smith, S. A., Choi, S. H., Morrissey, J. H., Gruber, A., & McCarty, O. J. (2013). Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates. Journal of Thrombosis and Haemostasis : JTH, 11(7), 1341-52. https://doi.org/10.1111/jth.12295
Puy C, et al. Factor XII Promotes Blood Coagulation Independent of Factor XI in the Presence of Long-chain Polyphosphates. J Thromb Haemost. 2013;11(7):1341-52. PubMed PMID: 23659638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates. AU - Puy,C, AU - Tucker,E I, AU - Wong,Z C, AU - Gailani,D, AU - Smith,S A, AU - Choi,S H, AU - Morrissey,J H, AU - Gruber,A, AU - McCarty,O J T, PY - 2012/11/13/received PY - 2013/5/11/entrez PY - 2013/5/11/pubmed PY - 2014/2/8/medline KW - factor XI KW - factor XII KW - polyphosphate KW - thrombin generation KW - thrombosis SP - 1341 EP - 52 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 11 IS - 7 N2 - BACKGROUND: Inorganic polyphosphates (polyP), which are secreted by activated platelets (short-chain polyP) and accumulate in some bacteria (long-chain polyP), support the contact activation of factor XII (FXII) and accelerate the activation of FXI. OBJECTIVES: The aim of the present study was to evaluate the role of FXI in polyP-mediated coagulation activation and experimental thrombus formation. METHODS AND RESULTS: Pretreatment of plasma with antibodies that selectively inhibit FXI activation by activated FXII (FXIIa) or FIX) activation by activated FXI (FXIa) were not able to inhibit the procoagulant effect of long or short-chain polyP in plasma. In contrast, the FXIIa inhibitor, corn trypsin inhibitor, blocked the procoagulant effect of long and short polyP in plasma. In a purified system, long polyP significantly enhanced the rate of FXII and prekallikrein activation and the activation of FXI by thrombin but not by FXIIa. In FXI-deficient plasma, long polyP promoted clotting of plasma in an FIX-dependent manner. In a purified system, the activation of FXII and prekallikrein by long polyP promoted FIX activation and prothombin activation. In an ex vivo model of occlusive thrombus formation, inhibition of FXIIa with corn trypsin inhibitor but not of FXI with a neutralizing antibodies abolished the prothrombotic effect of long polyP. CONCLUSIONS: We propose that long polyP promotes FXII-mediated blood coagulation bypassing FXI. Accordingly, some polyp-containing pathogens may have evolved strategies to exploit polyP-initiated FXII activation for virulence, and selective inhibition of FXII may improve the host response to pathogens. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/23659638/Factor_XII_promotes_blood_coagulation_independent_of_factor_XI_in_the_presence_of_long_chain_polyphosphates_ L2 - https://doi.org/10.1111/jth.12295 DB - PRIME DP - Unbound Medicine ER -