{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:23:53Z","timestamp":1790429033115,"version":"4.1.0"},"reference-count":60,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Storage lesion\u2013induced, red cell\u2013derived microvesicles (RBC-MVs) propagate coagulation by supporting the assembly of the prothrombinase complex. It has also been reported that RBC-MVs initiate coagulation via the intrinsic pathway. To elucidate the mechanism(s) of RBC-MV\u2013induced coagulation activation, the ability of storage lesion\u2013induced RBC-MVs to activate each zymogen of the intrinsic pathway was assessed in a buffer system. Simultaneously, the thrombin generation (TG) assay was used to assess their ability to initiate coagulation in plasma. RBC-MVs directly activated factor XII (FXII) or prekallikrein, but not FXI or FIX. RBC-MVs initiated TG in normal pooled plasma and in FXII- or FXI-deficient plasma, but not in FIX-deficient plasma, suggesting an alternate pathway that bypasses both FXII and FXI. Interestingly, RBC-MVs generated FIXa in a prekallikrein-dependent manner. Similarly, purified kallikrein activated FIX in buffer and initiated TG in normal pooled plasma, as well as FXII- or FXI-deficient plasma, but not FIX-deficient plasma. Dual inhibition of FXIIa by corn trypsin inhibitor and kallikrein by soybean trypsin inhibitor was necessary for abolishing RBC-MV\u2013induced TG in normal pooled plasma, whereas kallikrein inhibition alone was sufficient to abolish TG in FXII- or FXI-deficient plasma. Heating RBC-MVs at 60\u00b0C for 15 minutes or pretreatment with trypsin abolished TG, suggesting the presence of MV-associated proteins that are essential for contact activation. In summary, RBC-MVs activate both FXII and prekallikrein, leading to FIX activation by 2 independent pathways: the classic FXIIa-FXI-FIX pathway and direct kallikrein activation of FIX. These data suggest novel mechanisms by which RBC transfusion mediates inflammatory and\/or thrombotic outcomes.<\/jats:p>","DOI":"10.1182\/blood.2019001643","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T14:19:44Z","timestamp":1579789184000},"page":"755-765","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":88,"title":["Red blood cell microvesicles activate the contact system, leading to factor IX activation via 2 independent pathways"],"prefix":"10.1182","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-345X","authenticated-orcid":false,"given":"Denis F.","family":"Noubouossie","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Henderson","sequence":"first","affiliation":[{"name":"UNC Blood Research Center, and"},{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Mooberry","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7669-0760","authenticated-orcid":false,"given":"Anton","family":"Ilich","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ellsworth","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Piegore","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-723X","authenticated-orcid":false,"given":"Sarah C.","family":"Skinner","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"},{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Pawlinski","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Welsby","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Duke University, Durham, NC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Renn\u00e9","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureane","family":"Hoffman","sequence":"first","affiliation":[{"name":"Department of Pathology, Veteran Affairs Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0493-2943","authenticated-orcid":false,"given":"Dougald M.","family":"Monroe","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-4304","authenticated-orcid":false,"given":"Nigel S.","family":"Key","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"UNC Blood Research Center, and"},{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"8","key":"2020030512011490900_B1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nri2567","article-title":"Membrane vesicles as conveyors of immune responses","volume":"9","author":"Th\u00e9ry","year":"2009","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"2020030512011490900_B2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2174\/187153006778249976","article-title":"Origin and biological significance of shed-membrane microparticles","volume":"6","author":"Tesse","year":"2006","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"issue":"10","key":"2020030512011490900_B3","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1161\/CIRCRESAHA.110.233056","article-title":"Microparticles in hemostasis and thrombosis","volume":"108","author":"Owens","year":"2011","journal-title":"Circ Res"},{"issue":"1","key":"2020030512011490900_B4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/trf.12804","article-title":"An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies","volume":"55","author":"D\u2019Alessandro","year":"2015","journal-title":"Transfusion"},{"issue":"2","key":"2020030512011490900_B5","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.transci.2015.10.010","article-title":"An overview of the role of microparticles\/microvesicles in blood components: are they clinically beneficial or harmful?","volume":"53","author":"Burnouf","year":"2015","journal-title":"Transfus Apheresis Sci"},{"issue":"3","key":"2020030512011490900_B6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000486137","article-title":"Characteristics of extracellular vesicles in red blood concentrates change with storage time and blood manufacturing method","volume":"45","author":"Almizraq","year":"2018","journal-title":"Transfus Med Hemother"},{"issue":"7","key":"2020030512011490900_B7","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1111\/j.1538-7836.2012.04758.x","article-title":"Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa","volume":"10","author":"Van Der Meijden","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"4","key":"2020030512011490900_B8","first-page":"751","article-title":"Red cell-derived microparticles (RMP) as haemostatic agent","volume":"110","author":"Jy","year":"2013","journal-title":"Thromb Haemost"},{"issue":"21","key":"2020030512011490900_B9","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1001\/archinte.168.21.2377","article-title":"Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer","volume":"168","author":"Khorana","year":"2008","journal-title":"Arch Intern Med"},{"issue":"9","key":"2020030512011490900_B10","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1001\/jamasurg.2018.1565","article-title":"Association of Perioperative Red Blood Cell Transfusions With Venous Thromboembolism in a North American Registry","volume":"153","author":"Goel","year":"2018","journal-title":"JAMA Surg"},{"issue":"3","key":"2020030512011490900_B11","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ahj.2012.07.003","article-title":"Adverse impact of bleeding and transfusion on the outcome post-transcatheter aortic valve implantation: insights from the Pooled-RotterdAm-Milano-Toulouse In Collaboration Plus (PRAGMATIC Plus) initiative","volume":"164","author":"Tchetche","year":"2012","journal-title":"Am Heart J"},{"issue":"5","key":"2020030512011490900_B12","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.thromres.2011.07.047","article-title":"Association of blood transfusion and venous thromboembolism after colorectal cancer resection","volume":"129","author":"Xenos","year":"2012","journal-title":"Thromb Res"},{"key":"2020030512011490900_B13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jss.2017.09.038","article-title":"The risk factors of venous thromboembolism in massively transfused patients","volume":"222","author":"Dhillon","year":"2018","journal-title":"J Surg Res"},{"key":"2020030512011490900_B14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jss.2016.08.072","article-title":"A simplified stratification system for venous thromboembolism risk in severely injured trauma patients","volume":"207","author":"Meizoso","year":"2017","journal-title":"J Surg Res"},{"key":"2020030512011490900_B15","unstructured":"Baumann Kreuziger L , EdgrenG, HauserRG, et al Red blood transfusion does not increase risk for venous or arterial thrombosis [abstract]. Blood. 2018;132(suppl 1). Abstract 415."},{"issue":"8","key":"2020030512011490900_B16","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1111\/trf.12008","article-title":"Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation","volume":"53","author":"Rubin","year":"2013","journal-title":"Transfusion"},{"key":"2020030512011490900_B17","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1159\/000494367","article-title":"Procoagulant activity of red blood cell-derived microvesicles during red cell storage","volume":"46","author":"Hashemi Tayer","year":"2019","journal-title":"Transfus Med Hemother"},{"issue":"4","key":"2020030512011490900_B18","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1097\/TA.0000000000001759","article-title":"Microparticles formed during storage of red blood cell units support thrombin generation","volume":"84","author":"Bouchard","year":"2018","journal-title":"J Trauma Acute Care Surg"},{"issue":"1","key":"2020030512011490900_B19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/vox.12014","article-title":"Elevated levels of thrombin-generating microparticles in stored red blood cells","volume":"105","author":"Gao","year":"2013","journal-title":"Vox Sang"},{"issue":"1","key":"2020030512011490900_B20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0005-2736(86)90302-0","article-title":"Vesicles of variable sizes produced by a rapid extrusion procedure","volume":"858","author":"Mayer","year":"1986","journal-title":"Biochim Biophys Acta"},{"issue":"12","key":"2020030512011490900_B21","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1182\/blood.V91.12.4581","article-title":"Blood coagulation in hemophilia A and hemophilia C","volume":"91","author":"Cawthern","year":"1998","journal-title":"Blood"},{"key":"2020030512011490900_B22","doi-asserted-by":"crossref","first-page":"12616","DOI":"10.1038\/ncomms12616","article-title":"Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection","volume":"7","author":"Labberton","year":"2016","journal-title":"Nat Commun"},{"issue":"6","key":"2020030512011490900_B23","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1111\/jth.12207","article-title":"Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop","volume":"11","author":"Lacroix","year":"2013","journal-title":"J Thromb Haemost"},{"issue":"1","key":"2020030512011490900_B24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1159\/000071636","article-title":"Calibrated automated thrombin generation measurement in clotting plasma","volume":"33","author":"Hemker","year":"2003","journal-title":"Pathophysiol Haemost Thromb"},{"issue":"4","key":"2020030512011490900_B25","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1160\/TH16-09-0691","article-title":"Nucleic acids as cofactors for factor XI and prekallikrein activation: different roles for high-molecular-weight kininogen","volume":"117","author":"Ivanov","year":"2017","journal-title":"Thromb Haemost"},{"issue":"3","key":"2020030512011490900_B26","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1046\/j.1525-1381.1999.99232.x","article-title":"Activation of the plasma kallikrein\/kinin system on endothelial cells","volume":"111","author":"R\u00f8jkjaer","year":"1999","journal-title":"Proc Assoc Am Physicians"},{"issue":"7","key":"2020030512011490900_B27","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1111\/jth.12295","article-title":"Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates","volume":"11","author":"Puy","year":"2013","journal-title":"J Thromb Haemost"},{"issue":"3","key":"2020030512011490900_B28","first-page":"553","article-title":"The activation of human factor IX","volume":"33","author":"Osterud","year":"1975","journal-title":"Thromb Diath Haemorrh"},{"issue":"4","key":"2020030512011490900_B29","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1182\/blood.V64.4.821.821","article-title":"Cleavage and activation of human factor IX by serine proteases","volume":"64","author":"Enfield","year":"1984","journal-title":"Blood"},{"issue":"4","key":"2020030512011490900_B30","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3109\/10409238.2015.1050550","article-title":"How it all starts: initiation of the clotting cascade","volume":"50","author":"Smith","year":"2015","journal-title":"Crit Rev Biochem Mol Biol"},{"issue":"2","key":"2020030512011490900_B31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.transci.2017.03.007","article-title":"Extracellular vesicle characteristics in stored red blood cell concentrates are influenced by the method of detection","volume":"56","author":"Almizraq","year":"2017","journal-title":"Transfus Apheresis Sci"},{"issue":"5","key":"2020030512011490900_B32","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1182\/blood-2013-10-530469","article-title":"Exosomes from red blood cell units bind to monocytes and induce proinflammatory cytokines, boosting T-cell responses in vitro","volume":"123","author":"Danesh","year":"2014","journal-title":"Blood"},{"issue":"11","key":"2020030512011490900_B33","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1084\/jem.20021868","article-title":"Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin","volume":"197","author":"Falati","year":"2003","journal-title":"J Exp Med"},{"key":"2020030512011490900_B34","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.3389\/fimmu.2017.01188","article-title":"The procoagulant activity of apoptotic cells is mediated by interaction with factor XII","volume":"8","author":"Yang","year":"2017","journal-title":"Front Immunol"},{"issue":"15","key":"2020030512011490900_B35","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1021\/bi00336a047","article-title":"Binding and activation properties of human factor XII, prekallikrein, and derived peptides with acidic lipid vesicles","volume":"24","author":"Griep","year":"1985","journal-title":"Biochemistry"},{"issue":"9","key":"2020030512011490900_B36","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.4049\/jimmunol.1302590","article-title":"High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase plasminogen activator receptor-mediated efferocytosis","volume":"192","author":"Yang","year":"2014","journal-title":"J Immunol"},{"issue":"20","key":"2020030512011490900_B37","doi-asserted-by":"crossref","first-page":"17962","DOI":"10.1074\/jbc.M106101200","article-title":"Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator","volume":"277","author":"Shariat-Madar","year":"2002","journal-title":"J Biol Chem"},{"issue":"2","key":"2020030512011490900_B38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.transci.2015.10.012","article-title":"Differences between calcium-stimulated and storage-induced erythrocyte-derived microvesicles","volume":"53","author":"Prudent","year":"2015","journal-title":"Transfus Apheresis Sci"},{"issue":"23","key":"2020030512011490900_B39","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1056\/NEJMoa0803200","article-title":"Contaminated heparin associated with adverse clinical events and activation of the contact system","volume":"358","author":"Kishimoto","year":"2008","journal-title":"N Engl J Med"},{"issue":"46","key":"2020030512011490900_B40","doi-asserted-by":"crossref","first-page":"29023","DOI":"10.1074\/jbc.271.46.29023","article-title":"Identification of a factor IX binding site on the third apple domain of activated factor XI","volume":"271","author":"Sun","year":"1996","journal-title":"J Biol Chem"},{"issue":"11","key":"2020030512011490900_B41","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.3324\/haematol.2009.008938","article-title":"Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease","volume":"94","author":"van Beers","year":"2009","journal-title":"Haematologica"},{"issue":"1","key":"2020030512011490900_B42","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1186\/cc10032","article-title":"Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study","volume":"15","author":"Tuinman","year":"2011","journal-title":"Crit Care"},{"issue":"2","key":"2020030512011490900_B43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/jth.14360","article-title":"Red blood cells: the forgotten player in hemostasis and thrombosis","volume":"17","author":"Weisel","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"16","key":"2020030512011490900_B44","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1182\/blood-2017-03-745349","article-title":"Red blood cells in thrombosis","volume":"130","author":"Byrnes","year":"2017","journal-title":"Blood"},{"issue":"2","key":"2020030512011490900_B45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.surg.2017.09.028","article-title":"Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion","volume":"163","author":"Kim","year":"2018","journal-title":"Surgery"},{"issue":"5","key":"2020030512011490900_B46","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1186\/cc8050","article-title":"Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries","volume":"13","author":"Spinella","year":"2009","journal-title":"Crit Care"},{"issue":"6","key":"2020030512011490900_B47","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.annemergmed.2018.09.033","article-title":"Older blood is associated with increased mortality and adverse events in massively transfused trauma patients: secondary analysis of the PROPPR trial","volume":"73","author":"Jones","year":"2019","journal-title":"Ann Emerg Med"},{"issue":"7","key":"2020030512011490900_B48","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1111\/trf.13047","article-title":"Hypotensive transfusion reactions in the era of prestorage leukoreduction","volume":"55","author":"Pagano","year":"2015","journal-title":"Transfusion"},{"issue":"2","key":"2020030512011490900_B49","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1084\/jem.20050664","article-title":"Defective thrombus formation in mice lacking coagulation factor XII","volume":"202","author":"Renn\u00e9","year":"2005","journal-title":"J Exp Med"},{"issue":"11","key":"2020030512011490900_B50","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1182\/blood-2013-04-499111","article-title":"Factor XII inhibition reduces thrombus formation in a primate thrombosis model","volume":"123","author":"Matafonov","year":"2014","journal-title":"Blood"},{"issue":"3","key":"2020030512011490900_B51","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1182\/blood-2007-06-092338","article-title":"Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis","volume":"111","author":"Merkulov","year":"2008","journal-title":"Blood"},{"issue":"6","key":"2020030512011490900_B52","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1160\/TH11-10-0682","article-title":"Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait","volume":"107","author":"Bird","year":"2012","journal-title":"Thromb Haemost"},{"key":"2020030512011490900_B53","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.thromres.2016.02.020","article-title":"A comparison of the effects of factor XII deficiency and prekallikrein deficiency on thrombus formation","volume":"140","author":"Kokoye","year":"2016","journal-title":"Thromb Res"},{"issue":"1","key":"2020030512011490900_B54","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1182\/asheducation-2014.1.66","article-title":"Epidemiologic and clinical data linking factors XI and XII to thrombosis","volume":"2014","author":"Key","year":"2014","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"6","key":"2020030512011490900_B55","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.blre.2018.04.001","article-title":"Plasma contact factors as therapeutic targets","volume":"32","author":"Tillman","year":"2018","journal-title":"Blood Rev"},{"issue":"2","key":"2020030512011490900_B56","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1182\/blood-2016-09-692996","article-title":"Emerging anticoagulant strategies","volume":"129","author":"Fredenburgh","year":"2017","journal-title":"Blood"},{"key":"2020030512011490900_B57","doi-asserted-by":"crossref","unstructured":"Schmaier AH , BauerKA, CicardiM, et al Effect of lanadelumab on coagulation parameters in patients with hereditary angioedema: findings from the phase 3 HELP study [abstract]. J Allergy Clin Immunol. 2019;143(2). Abstract AB41.","DOI":"10.1016\/j.jaci.2018.12.123"},{"issue":"3","key":"2020030512011490900_B58","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.1432-1033.1987.tb11174.x","article-title":"Studies on the effect of serine protease inhibitors on activated contact factors. Application in amidolytic assays for factor XIIa, plasma kallikrein and factor XIa","volume":"164","author":"Tans","year":"1987","journal-title":"Eur J Biochem"},{"issue":"3","key":"2020030512011490900_B59","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0021-9258(18)91866-1","article-title":"Interaction of soybean trypsin inhibitor with thrombin and its effect on prothrombin activation","volume":"244","author":"Lanchantin","year":"1969","journal-title":"J Biol Chem"},{"issue":"18","key":"2020030512011490900_B60","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1182\/bloodadvances.2018021931","article-title":"Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity","volume":"2","author":"Almizraq","year":"2018","journal-title":"Blood Adv"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/135\/10\/755\/1717895\/bloodbld2019001643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/135\/10\/755\/1717895\/bloodbld2019001643.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T14:07:17Z","timestamp":1614089237000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/135\/10\/755\/431281\/Red-blood-cell-microvesicles-activate-the-contact"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,5]]},"references-count":60,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,3,5]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2019001643","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,5]]}}}