Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants
Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants
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DOI：
10.1111/j.1399-3089.2011.00621.x
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发表时间：
2011-01-01
影响因子：
3.9
通讯作者：
Lin, Shu S.
中科院分区：
文献类型：
--
作者：
Bush, Errol L.;Barbas, Andrew S.;Lin, Shu S.
背景资料：在许多方面取得实质性进展后，仍然反对异种移植临床应用的剩余障碍之一是在猪到灵长类动物移植的临床前模型中观察到的弥散性血管内凝血病（DIC）。DIC的发病在肺异种移植物的接受者中特别迅速，通常发生在再灌注的最初几天甚至几个小时内。方法：在这项研究中，我们描述了两个猪到狒狒移植的结果，利用猪肺耗尽巨噬细胞，缺乏α-1，3-半乳糖基转移酶基因，并表达人衰变加速因子，一种补体调节蛋白。结果：在这两种情况下，DIC的证据内观察到再灌注48小时，血小板减少症和凝血酶-抗凝血酶复合物的水平增加，在这两种情况下明显。在一个移植物中观察到纤维蛋白原的消耗，而在另一个移植物中观察到D-二聚体水平的升高。一个移植物，这表明局灶性淋巴细胞浸润术前，在3小时内失败。结论：结果表明，需要进一步努力，以解决与异种肺移植相关的凝血功能障碍。此外，有证据表明，常驻猪免疫细胞可在与异种移植相关的凝血病中发挥重要作用。
Background: After substantial progress on many fronts, one of the remaining barriers still opposing the clinical application of xenotransplantation is a disseminated intravascular coagulopathy (DIC) that is observed in the pre-clinical model of porcine-to-primate transplantation. The onset of DIC is particularly rapid in recipients of pulmonary xenografts, usually occurring within the first days or even hours of reperfusion.Methods: In this study, we describe the results of two porcine-to-baboon transplants utilizing porcine lungs depleted of macrophages, deficient in the alpha-1,3-galactosyltransferase gene, and with the expression of human decay-accelerating factor, a complement regulatory protein.Results: In both cases, evidence of DIC was observed within 48 h of reperfusion, with thrombocytopenia and increases in levels of thrombin-antithrombin complex evident in both cases. Depletion of fibrinogen was observed in one graft, whereas elevation of D-dimer levels was observed in the other. One graft, which showed focal lymphocytic infiltrates pre-operatively, failed within 3 h.Conclusions: The results indicate that further efforts to address the coagulopathy associated with pulmonary xenotransplantation are needed. Further, evidence suggests that resident porcine immune cells can play an important role in the coagulopathy associated with xenotransplantation.