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Most advances in this field have resulted from the introduction of genetically engineered pigs, e.g., \u03b11,3\u2010galactosyltransferase gene\u2010knockout (<jats:styled-content style=\"fixed-case\">GTKO<\/jats:styled-content>) pigs transgenic for one or more human complement\u2010regulatory proteins (e.g., <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>55, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>59). Failure of these grafts has not been associated with the classical features of acute humoral xenograft rejection, but with the development of thrombotic microangiopathy in the graft and\/or consumptive coagulopathy in the recipient. Although the precise mechanisms of coagulation dysregulation remain unclear, molecular incompatibilities between primate coagulation factors and pig natural anticoagulants exacerbate the thrombotic state within the xenograft vasculature. Platelets play a crucial role in thrombosis and contribute to the coagulation disorder in xenotransplantation. They are therefore important targets if this barrier is to be overcome. Further genetic manipulation of the organ\u2010source pigs, such as pigs that express one or more coagulation\u2010regulatory genes (e.g., thrombomodulin, endothelial protein C receptor, tissue factor pathway inhibitor, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>39), is anticipated to inhibit platelet activation and the generation of thrombus. In addition, adjunctive pharmacologic anti\u2010platelet therapy may be required. The genetic manipulations that are currently being tested are reviewed, as are the potential pharmacologic agents that may prove beneficial.<\/jats:p>","DOI":"10.1111\/xen.12085","type":"journal-article","created":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T07:25:01Z","timestamp":1393485901000},"page":"201-220","source":"Crossref","is-referenced-by-count":38,"title":["The role of platelets in coagulation dysfunction in xenotransplantation, and therapeutic options"],"prefix":"10.1111","volume":"21","author":[{"given":"Hayato","family":"Iwase","sequence":"first","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed B.","family":"Ezzelarab","sequence":"additional","affiliation":[{"name":"Thomas E. 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