Activation of platelets by heparin-induced thrombocytopenia antibodies in the serotonin release assay is not dependent on the presence of heparin
Activation of platelets by heparin-induced thrombocytopenia antibodies in the serotonin release assay is not dependent on the presence of heparin
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DOI：
10.1111/j.1538-7836.2005.01560.x
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发表时间：
2005-10-01
影响因子：
10.4
通讯作者：
Walenga, JM
中科院分区：
文献类型：
--
作者：
Prechel, MM;McDonald, MK;Walenga, JM
血清素释放测定 (SRA) 可检测导致肝素诱导的血小板减少症 (HIT) 的抗体。根据定义，在存在低浓度肝素的情况下，SRA 阳性抗体会在体外引起血小板血清素释放，但在存在过量肝素的情况下则不会。许多 SRA 阳性血清在不含药物的盐水存在下激活血小板，这要么是由于样本中残留肝素，要么是因为 HIT 抗体的固有特征。目前的实验表明，彻底的肝素酶处理和肝素的层析去除都不能消除由这些HIT抗体引起的自发血小板活化。这是第一项系统地证明 HIT 抗体的体外活性可以独立于肝素的研究。此外，T-gel 色谱法证明了各个样本中酶联免疫吸附测定 (ELISA) 阳性 HIT 抗体分数之间的差异。某些 ELISA 阳性级分具有 SRA 活性，而其他级分则没有，并且 SRA 活性与 HIT 抗体 ELISA 效价不成正比。这些数据表明，肝素治疗形成的抗体是异质的，即使肝素不再存在，某些抗体也可能导致 HIT 的发病机制。
The serotonin release assay (SRA) tests for antibodies responsible for heparin-induced thrombocytopenia (HIT). By definition, SRA-positive antibodies cause platelet serotonin release in vitro, in the presence of low concentrations of heparin, but not with excess heparin. Many SRA-positive sera activate platelets in the presence of saline without drug, either as a result of residual heparin in the specimen, or because of intrinsic features of the HIT antibodies. The present experiments show that neither exhaustive heparinase treatment, nor chromatographic removal of heparin abrogates the spontaneous platelet activation caused by these HIT antibodies. This is the first study to systematically demonstrate that in vitro activity of HIT antibodies can be independent of heparin. In addition, T-gel chromatography demonstrated differences among fractions of enzyme-linked-immunosorbent assay (ELISA)-positive HIT antibodies within individual specimens. Certain ELISA-positive fractions had SRA activity while others did not, and the SRA activity was not proportional to HIT antibody ELISA titer. These data suggest that antibodies formed as a result of heparin treatment are heterogeneous, and that some can contribute to the pathogenesis of HIT even when heparin is no longer present.