{"id":2315,"date":"2017-11-13T21:47:56","date_gmt":"2017-11-14T02:47:56","guid":{"rendered":"https:\/\/med.sites.unc.edu\/wolberglab\/new-publication-in-the-journal-of-thrombosis-and-haemostasis\/"},"modified":"2020-07-27T09:38:16","modified_gmt":"2020-07-27T13:38:16","slug":"new-publication-in-the-journal-of-thrombosis-and-haemostasis","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/wolberglab\/new-publication-in-the-journal-of-thrombosis-and-haemostasis\/","title":{"rendered":"New publication in the Journal of Thrombosis and Haemostasis"},"content":{"rendered":"<h3 class=\"citation__title\"><a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/jth.13887?campaign=wolacceptedarticle\">Factor XIII cotreatment with hemostatic agents in hemophilia A increases fibrin \u03b1\u2010chain crosslinking<\/a><\/h3>\n<p><strong>Background<\/strong>: Hemophilia A results from the absence, deficiency or inhibition of factor VIII . Bleeding is treated with hemostatic agents (FVIII , recombinant activated FVII [rFVII a], anti\u2010inhibitor coagulation complex [FEIBA ], or recombinant porcine FVIII [rpFVIII ]). Despite treatment, some patients have prolonged bleeding. FXIII \u2010A<sub>2<\/sub>B<sub>2<\/sub> (FXIII ) is a protransglutaminase. During clot contraction, thrombin\u2010activated FXIII (FXIII a) crosslinks fibrin and \u03b1<sub>2<\/sub>\u2010antiplasmin, which promotes red blood cell retention and increases clot stability and weight. We hypothesized that FXIII cotreatment in hemophilia would accelerate FXIII activation, leading to increased fibrin crosslinking. <strong>Methods<\/strong>: FVIII \u2010deficient plasma and whole blood were clotted with or without hemostatic agents (FVIII , rFVII a, FEIBA , or recombinant B\u2010domain\u2010deleted porcine FVIII [rpFVIII ]) and\/or FXIII . The effects on FXIII activation, thrombin generation, fibrin and \u03b1<sub>2<\/sub>\u2010antiplasmin crosslinking, clot formation and clot weight were measured by western blotting, calibrated automated thrombography, thromboelastography, and clot contraction assays. <strong>Results<\/strong>: As compared with FVIII \u2010treated hemophilic plasma, FVIII + FXIII cotreatment accelerated FXIII a formation without increasing thrombin generation. As compared with buffer\u2010treated or FXIII \u2010treated hemophilic plasma, FVIII treatment and FVIII + FXIII cotreatment increased the generation and amount of crosslinked fibrin, including \u03b1\u2010chain\u2010rich high molecular weight species and crosslinked \u03b1<sub>2<\/sub>\u2010antiplasmin. In the presence of FVIII inhibitors, as compared with hemostatic treatments (rFVII a, FEIBA , or rpFVIII ) alone, FXIII cotreatment increased whole blood clot weight. <strong>Conclusion<\/strong>: In hemophilia A plasma and whole blood, FXIII cotreatment with hemostatic agents accelerated FXIII a formation, increased the generation and amount of fibrin \u03b1\u2010chain crosslinked species, accelerated \u03b1<sub>2<\/sub>\u2010antiplasmin crosslinking, and increased clot weight. FXIII cotreatment with hemostatic therapy may augment hemostasis through increased crosslinking of fibrin and \u03b1<sub>2<\/sub>\u2010antiplasmin.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Factor XIII cotreatment with hemostatic agents in hemophilia A increases fibrin \u03b1\u2010chain crosslinking Background: Hemophilia A results from the absence, deficiency or inhibition of factor VIII . Bleeding is treated with hemostatic agents (FVIII , recombinant activated FVII [rFVII a], anti\u2010inhibitor coagulation complex [FEIBA ], or recombinant porcine FVIII [rpFVIII ]). Despite treatment, some patients &hellip; <a href=\"https:\/\/www.med.unc.edu\/wolberglab\/new-publication-in-the-journal-of-thrombosis-and-haemostasis\/\" aria-label=\"Read more about New publication in the Journal of Thrombosis and Haemostasis\">Read more<\/a><\/p>\n","protected":false},"author":49326,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[],"class_list":["post-2315","post","type-post","status-publish","format-standard","hentry","category-news","odd"],"acf":[],"featured_image":false,"featured_image_medium":false,"featured_image_medium_large":false,"featured_image_large":false,"featured_image_thumbnail":false,"featured_image_alt":false,"category_details":[{"name":"News","link":"https:\/\/www.med.unc.edu\/wolberglab\/category\/news\/"}],"tag_details":[],"_links_to":[],"_links_to_target":[],"_links":{"self":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/posts\/2315","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/users\/49326"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/comments?post=2315"}],"version-history":[{"count":0,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/posts\/2315\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/media?parent=2315"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/categories?post=2315"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.med.unc.edu\/wolberglab\/wp-json\/wp\/v2\/tags?post=2315"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}