{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T21:51:01Z","timestamp":1774907461297,"version":"3.50.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Terminal complications of bacterial sepsis include development of disseminated intravascular consumptive coagulopathy. Bacterial constituents, including long-chain polyphosphates (polyP), have been shown to activate the contact pathway of coagulation in plasma. Recent work shows that activation of the contact pathway in flowing whole blood promotes thrombin generation and platelet activation and consumption distal to thrombus formation ex vivo and in vivo. Here, we sought to determine whether presence of long-chain polyP or bacteria in the bloodstream promotes platelet activation and consumption in a coagulation factor (F)XII-dependent manner.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Long-chain polyP promoted platelet P-selectin expression, microaggregate formation, and platelet consumption in flowing whole blood in a contact activation pathway-dependent manner. Moreover, long-chain polyP promoted local fibrin formation on collagen under shear flow in a FXI-dependent manner. Distal to the site of thrombus formation, platelet consumption was dramatically enhanced in the presence of long-chain polyP in the blood flow in a FXI- and FXII-dependent manner. In a murine model, long-chain polyP promoted platelet deposition and fibrin generation in lungs in a FXII-dependent manner. In a nonhuman primate model of bacterial sepsis, pre-treatment of animals with an antibody blocking FXI activation by FXIIa reduced lethal dose\n              <jats:sub>100<\/jats:sub>\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              \u2013induced platelet and fibrinogen consumption.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>This study demonstrates that bacterial-type long-chain polyP promotes platelet activation in a FXII-dependent manner in flowing blood, which may contribute to sepsis-associated thrombotic processes, consumptive coagulopathy, and thrombocytopenia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311193","type":"journal-article","created":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T19:04:08Z","timestamp":1537211048000},"page":"1748-1760","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Factor XII Activation Promotes Platelet Consumption in the Presence of Bacterial-Type Long-Chain Polyphosphate In Vitro and In Vivo"],"prefix":"10.1161","volume":"38","author":[{"given":"Jevgenia","family":"Zilberman-Rudenko","sequence":"first","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie E.","family":"Reitsma","sequence":"additional","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"},{"name":"Oregon Health &amp; Science University, Portland; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, The Netherlands (S.E.R., C.M., R.T.U.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Puy","sequence":"additional","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A.","family":"Rigg","sequence":"additional","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry &amp; Internal Medicine, University of Michigan Medical School, Ann Arbor (S.A.S., J.H.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik I.","family":"Tucker","sequence":"additional","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"},{"name":"Aronora Inc, Portland, OR (E.I.T., A.G.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Silasi","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (R.S., F.L.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alona","family":"Merkulova","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH (A.M., AH.S.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith R.","family":"McCrae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coen","family":"Maas","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University, Portland; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, The Netherlands (S.E.R., C.M., R.T.U.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf T.","family":"Urbanus","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University, Portland; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, The Netherlands (S.E.R., C.M., R.T.U.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Gailani","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, TN (D.G.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Departments of Biological Chemistry &amp; Internal Medicine, University of Michigan Medical School, Ann Arbor (S.A.S., J.H.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e1s","family":"Gruber","sequence":"additional","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"},{"name":"Division of Hematology (A.G., O.J.T.M.)"},{"name":"Aronora Inc, Portland, OR (E.I.T., A.G.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florea","family":"Lupu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (R.S., F.L.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvin H.","family":"Schmaier","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH (A.M., AH.S.)"},{"name":"Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, OH (A.H.S.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen J.T.","family":"McCarty","sequence":"additional","affiliation":[{"name":"From the Biomedical Engineering, School of Medicine (J.Z.-R., S.E.R., C.P., R.A.R., E.I.T., A.G., O.J.T.M.)"},{"name":"Division of Hematology (A.G., O.J.T.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208623"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.22.4.f184"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-199208"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2015.1050550"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.39"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00195.x"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01304.x"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270918"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.307034"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-016-0448-5"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-386185"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-163675"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406261200"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.89"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-306605"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH14-06-0515"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-266791"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-368811"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12295"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-203604"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-499111"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050664"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-604587"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12707"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.553735"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13773"},{"key":"e_1_3_5_28_2","first-page":"403","article-title":"[Inorganic polyphosphate metabolism in Staphylococcus aureus and the action on it of antibiotics].","volume":"23","author":"Konoshenko GI","year":"1978","unstructured":"Konoshenko, GI, Polin, AN. [Inorganic polyphosphate metabolism in Staphylococcus aureus and the action on it of antibiotics]. Antibiotiki. 1978;23:403\u2013405.","journal-title":"Antibiotiki"},{"key":"e_1_3_5_29_2","first-page":"179","article-title":"Nickel sequestering by polyphosphate bodies in Staphylococcus aureus.","volume":"93","author":"Gonzalez H","year":"1998","unstructured":"Gonzalez, H, Jensen, TE. Nickel sequestering by polyphosphate bodies in Staphylococcus aureus. Microbios. 1998;93:179\u2013185.","journal-title":"Microbios"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043632"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-013-0361-1"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.4.2864"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.09019.x"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103109"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-734988"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(16)30354-1"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165172"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-04-641472"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12616"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-58444-2_6"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807563105"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408126200"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3433"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.69.7.3849-3857.2003"},{"key":"e_1_3_5_45_2","first-page":"67","article-title":"Severe hypophosphatemia in sepsis as a mortality predictor.","volume":"36","author":"Shor R","year":"2006","unstructured":"Shor, R, Halabe, A, Rishver, S, Tilis, Y, Matas, Z, Fux, A, Boaz, M, Weinstein, J. Severe hypophosphatemia in sepsis as a mortality predictor. Ann Clin Lab Sci. 2006;36:67\u201372.","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.9.3703-3710.1993"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.157.6.2049"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.001"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12899"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-529602"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110898"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-699561"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.118.311193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:43:48Z","timestamp":1715553828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.118.311193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1161\/ATVBAHA.118.311193"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.118.311193","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8]]},"assertion":[{"value":"2016-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}