Background

Platelet refractoriness remains a challenging clinical dilemma although significant advancements have been made in identifying human leukocyte antigen (HLA) matched or HLA compatible units. Antiplatelet antibodies are the major risk factor for immune-mediated platelet refractoriness, yet the role of antibody-initiated complement-mediated platelet destruction remains poorly understood.

Study Design and Methods

Human complement-mediated opsonization and killing of platelets was assayed ex vivo using antibody-sensitized human platelets incubated with complement-sufficient human sera. A new animal model of platelet refractoriness utilizing Wistar rats transfused with human platelets is described.

Results

Human platelets sensitized with anti-platelet antibodies were rapidly opsonized with iC3b upon incubation in human sera. This opsonization could be completely blocked with a classical pathway complement inhibitor, PA-dPEG24. Complement activation decreased platelet viability, which was also reversible with complement inhibitor PA-dPEG24. A new rat model of platelet refractoriness was developed that demonstrated some platelet removal from the blood stream was complement mediated.

Conclusions

Complement activation initiated by anti-platelet antibodies leads to complement opsonization and decreased platelet viability. A new rat model of platelet refractoriness was developed that adds a new tool for elucidating the mechanisms of platelet refractoriness.

中文翻译：

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补体介导的大鼠血小板不应性异种输血模型。

背景

尽管在鉴定人白细胞抗原（HLA）匹配或HLA兼容单位方面取得了重大进展，但血小板不应性仍是一个具有挑战性的临床难题。抗血小板抗体是免疫介导的血小板难治性的主要危险因素，然而，抗体引发的补体介导的血小板破坏的作用仍然知之甚少。

研究设计和方法

使用与补体充足的人血清一起温育的抗体致敏的人血小板，离体测定人补体介导的调理作用和对血小板的杀死。描述了使用输注人血小板的Wistar大鼠建立的血小板难治性新动物模型。

结果

在人血清中温育后，用iC3b快速调理被抗血小板抗体致敏的人血小板。这种调理作用可以用经典途径补体抑制剂PA-dPEG24完全阻断。补体激活降低了血小板活力，这也可通过补体抑制剂PA-dPEG24逆转。建立了新的大鼠血小板耐火性模型，该模型表明补血介导了从血流中去除一些血小板。

结论

由抗血小板抗体引发的补体激活导致补体调理作用和降低的血小板活力。建立了新的大鼠血小板不应性模型，该模型增加了阐明血小板难治性机制的新工具。