{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:47:17Z","timestamp":1761630437321},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,1,8]],"date-time":"2007-01-08T00:00:00Z","timestamp":1168214400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold><jats:bold> Background:\u2002<\/jats:bold> Hyperacute rejection (HAR) and early graft failure (EGF) have been described in a minority of pig\u2010to\u2010baboon heart transplants using organs transgenic for human complement regulatory proteins (hCRP). Here we investigate the role of coagulation cascade activation in the pathogenesis of HAR and EGF in a consecutive series where a high incidence of these outcomes was observed.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Twenty\u2010eight na\u00efve wild\u2010caught <jats:italic>Papio anubis<\/jats:italic> baboons received heterotopic heart transplants from pigs transgenic for hDAF (n\u2003=\u200323) or hMCP (n\u2003=\u20035). Immunosuppression consisted of cyclosporine A, cyclophosphamide and MMF (n\u2003=\u200318) or anti\u2010CD154\u2003mAb (IDEC\u2010131) and ATG (n\u2003=\u200310). Eleven received anti\u2010Gal carbohydrates (GAS914, n\u2003=\u20038, or NEX1285, n\u2003=\u20033), of which four also underwent extracorporeal immunoadsorption (EIA), and 12 also received pharmacologic complement inhibitors (C1 INH, n\u2003=\u20039, or APT070, n\u2003=\u20033).<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Excluding one technical failure, 14 of 27 transplants (11\u2003hDAF, 3\u2003hMCP) exhibited either HAR (n\u2003=\u200310) or EGF (n\u2003=\u20034). Surprisingly, neither complement inhibition (with C1 INH or APT070) nor anti\u2010Gal antibody depletion with GAS914, NEX1285, or additional EIA consistently prevented HAR or EGF despite low or undetectable complement deposition. Strikingly, most grafts with HAR\/EGF exhibited prominent fibrinogen and platelet deposition associated with systemic coagulation cascade activation, consistent with non\u2010physiologic intravascular coagulation, in many instances despite little evidence for antibody\u2010mediated complement activation.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> We conclude that dysregulated coagulation correlates closely with and probably causes primary failure of pig hearts transgenic for hCRP. These data support efforts to define effective strategies to prevent dysregulated coagulation in pig organ xenografts.<\/jats:p>","DOI":"10.1111\/j.1399-3089.2006.00362.x","type":"journal-article","created":{"date-parts":[[2007,1,8]],"date-time":"2007-01-08T16:32:04Z","timestamp":1168273924000},"page":"34-47","source":"Crossref","is-referenced-by-count":35,"title":["Coagulation cascade activation triggers early failure of pig hearts expressing human complement regulatory 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