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We report an in vitro thrombogenicity assessment methodology where test materials (polyethylene, Elasthane\u2122 80A polyurethane, Pebax\u00ae), alongside positive (borosilicate glass) and negative (no material) controls, were exposed to fresh human blood, with attention to common blood\u2010contact use conditions and the variables: material (M), material surface modification (SM) with heparin, model (Mo), time (T), blood donor (D), exposure ratio (ER; cm<jats:sup>2<\/jats:sup> material\/ml blood), heparin anticoagulation (H), and blood draw\/fill technique (DT). Two models were used: (1) a gentle\u2010agitation test tube model and (2) a pulsatile flow closed\u2010loop model. Thrombogenicity measurements included thrombin generation (thrombin\u2010antithrombin complex [TAT] and human prothrombin fragment F1.2), platelet activation (\u03b2\u2010thromboglobulin), and platelet counts. We report that: (a) thrombogenicity was strongly dependent (<jats:italic>p<\/jats:italic> &lt;\u2009.0001) on M, H, and T, and variably dependent (<jats:italic>p<\/jats:italic> &lt;\u2009.0001 \u2013\u2009&gt;\u2009.05) on Mo, SM, and D (b) differences between positive control, test, and negative control materials became less pronounced as H increased from 0.6 to 2.0 U\/ml, and (c) in vitro\u2010to\u2010in vivo case comparisons showed consistency in thrombogenicity rankings on materials classified to be of low, moderate, and high concern. In vitro methods using fresh human blood are therefore scientifically sound and cost effective compared to in vivo methods for screening intravascular materials and devices for thrombogenicity.<\/jats:p>","DOI":"10.1002\/jbm.b.34705","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T07:41:29Z","timestamp":1600242089000},"page":"358-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof\u2010of\u2010concept approach"],"prefix":"10.1002","volume":"109","author":[{"given":"Michael F.","family":"Wolf","sequence":"first","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Girdhar","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle A.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha R.","family":"Ubl","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinduja","family":"Thinamany","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah N.","family":"Jeffers","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney E.","family":"DeRusha","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Rodriguez\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Core Technologies seh consulting + services  Paderborn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie A.","family":"Strief","sequence":"additional","affiliation":[{"name":"Core Technologies Medtronic  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-816137-1.00052-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-816137-1.00050-7"},{"key":"e_1_2_7_4_1","first-page":"159","volume-title":"Biocompatibility and Performance of Medical Devices","author":"Anderson JM","year":"2012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1559-4106-8-33"},{"key":"e_1_2_7_6_1","unstructured":"ASTMF2382 Standard Test Method for Assessment of Circulating Blood\u2010Contacting Medical Device Materials on Partial Thromboplastin Time (PTT) 2018."},{"key":"e_1_2_7_7_1","unstructured":"ASTMF2888 Standard Practice for Platelet Leukocyte Count\u2014An In\u2010Vitro Measure for Hemocompatibility Assessment of Cardiovascular Materials 2019."},{"key":"e_1_2_7_8_1","unstructured":"ISO 10993\u20104 Biological Evaluation of Medical Devices Part 4: Selection of tests for interactions with blood 2017."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1163\/156856200744246"},{"key":"e_1_2_7_10_1","volume-title":"Geigy Scientific Tables: Heart and Circulation","author":"Lentner C","year":"1991"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/673163"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36514"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ensci.2019.01.004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646768"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1647475"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V57.2.199.199"},{"key":"e_1_2_7_17_1","unstructured":"LareauR FacchiniF.A new option for short\u2010 or long\u2010term peripheral access to the central venous system. 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