Thrombocytopenia after pig-to-baboon liver xenotransplantation: where do platelets go?
Thrombocytopenia after pig-to-baboon liver xenotransplantation: where do platelets go?
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DOI：
10.1111/j.1399-3089.2011.00679.x
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发表时间：
2011-11-01
影响因子：
3.9
通讯作者：
Cooper, David K. C.
中科院分区：
文献类型：
--
作者：
Ezzelarab, Mohamed;Ekser, Burcin;Cooper, David K. C.
背景：移植同种异种猪肝的狒狒，在再灌注后1小时内观察到严重的血小板减少。对血小板命运的评估可能会揭示导致血小板减少的潜在机制，并可能允许引入预防性治疗。方法：用转染人CD46 （GTKO/CD46）的α 1,3-半乳糖转移酶基因敲除猪原位肝移植两只狒狒，观察其血小板-白细胞（WBC）聚集。流式细胞术测定cd42a阳性血小板聚集物与wbc亚型的百分比，并计算绝对数量（每mm3）。应用免疫荧光和电镜技术对异种肝脏移植中血小板聚集物进行了鉴定。测定移植前后平均血小板体积（MPV）。结果：猪肝再灌注后，深度血小板减少与白细胞亚型血小板聚集有关。在移植后直至受者安乐死期间，检测到白细胞亚型血小板聚集增加。血血小板计数与血小板与单核细胞、中性粒细胞聚集呈极显著负相关（P < 0.01），与淋巴细胞无显著负相关。MPV保持在正常范围内。再灌注2小时后，免疫荧光和电镜检测到异种肝移植物的血小板和纤维蛋白沉积。结论：异种肝移植后，血小板从循环中早期消失至少部分是由于它们与循环白细胞聚集，这可能增加了它们在异种肝移植和原生肺中的沉积。预防单核细胞和中性粒细胞的血小板聚集可能有助于减少它们随后在异种肝脏移植和原生器官中的隔离。
Background: In baboons with orthotopic pig liver xenografts, profound thrombocytopenia was observed within 1 h after reperfusion. Assessment of the fate of platelets may shed light on the underlying mechanisms leading to thrombocytopenia and may allow preventive therapies to be introduced.Methods: Plateletwhite blood cell (WBC) aggregation was studied in two baboons that received orthotopic liver xenografts from alpha 1,3-galactosyltransferase gene-knockout pigs transgenic for human CD46 (GTKO/CD46). Percentages of CD42a-positive platelet aggregates with WBC-subtypes were determined by flow cytometry, and absolute numbers (per mm3) were calculated. Platelet aggregates in the liver xenografts were identified by immunofluorescence and electron microscopy. Mean platelet volume (MPV) was determined before and after transplantation.Results: After pig liver reperfusion, profound thrombocytopenia was associated with aggregation of platelets with WBC-subtypes. Increasing aggregation of platelets with WBC-subtypes was detected throughout the post-transplant period until the recipient was euthanized. Significant negative correlation was found between platelet counts in the blood and aggregation of platelets with monocytes (P < 0.01) and neutrophils (P < 0.01), but not with lymphocytes. MPV remained within the normal range. Two hours after reperfusion, platelet and fibrin deposition were already detected in the liver xenografts by immunofluorescence and by electron microscopy.Conclusions: Following liver xenotransplantation, the early disappearance of platelets from the circulation was at least in part due to their aggregation with circulating WBC, which may augment their deposition in the liver xenograft and native lungs. Prevention of platelet aggregation with monocytes and neutrophils is likely beneficial in reducing their subsequent sequestration in the liver xenograft and native organs.