FcRIIa proteolysis as a diagnostic biomarker for heparin-induced thrombocytopenia
FcRIIa proteolysis as a diagnostic biomarker for heparin-induced thrombocytopenia
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DOI：
10.1111/jth.12208
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发表时间：
2013-06-01
影响因子：
10.4
通讯作者：
Kelton, J. G.
中科院分区：
文献类型：
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作者：
Nazi, I.;Arnold, D. M.;Kelton, J. G.
肝素诱导的血小板减少症（HIT）患者的治疗面临的一个重大挑战是及时准确的诊断。酶免疫法（EIA）特异性低。相比之下，血小板活化测定具有更高的特异性，但它们在技术上要求很高，并且不能广泛使用。此外，大约10%的HIT检测样本最初被血清素释放试验（SRA）归类为不确定，这进一步延迟了准确的诊断。HIT的特征在于血小板活化，其导致FcRIIa蛋白水解。这提出了可能性，鉴定的蛋白水解片段的FcRIIa可以作为一个替代标记物为HIT.ObjectivesTo确定特异性的血小板FcRIIa蛋白水解诱导的血清从HIT患者，并与那些SRA.Methods/PatientsSera从HIT患者和对照患者与其他血小板减少/血栓前疾病进行了测试，他们的能力，以蛋白水解FcRIIa。结果与抗血小板因子4（PF 4）/肝素抗体（EIA），肝素依赖性血小板活化（SRA）。ResultsOnly HIT患者样本（20/20）引起肝素依赖性FcRIIa蛋白水解，类似于所示的SRA。来自其他患者组或医院对照的样品均未引起FcRIIa蛋白水解。在SRA中检测为不确定的另外9个样本中，FcRIIa蛋白水解解决了5个具有阳性抗PF 4/肝素EIA结果的样本; 3个没有FcRIIa蛋白水解，2个显示具有肝素依赖性FcRIIa蛋白水解。结论本研究表明，肝素依赖性FcRIIa蛋白水解至少与SRA一样特异性用于诊断HIT。
BackgroundA significant challenge in the management of heparin-induced thrombocytopenia (HIT) patients is making a timely and accurate diagnosis. The readily available enzyme immunoassays (EIAs) have low specificities. In contrast, platelet activation assays have higher specificities, but they are technically demanding and not widely available. In addition, similar to 10% of samples referred for HIT testing are initially classified as indeterminate by the serotonin release assay (SRA), which further delays accurate diagnosis. HIT is characterized by platelet activation, which leads to FcRIIa proteolysis. This raises the possibility that identification of the proteolytic fragment of FcRIIa could serve as a surrogate marker for HIT.ObjectivesTo determine the specificity of platelet FcRIIa proteolysis induced by sera from patients with HIT, and to correlate the results with those of the SRA.Methods/PatientsSera from HIT patients and control patients with other thrombocytopenic/prothrombotic disorders were tested for their ability to proteolyse FcRIIa. The results were correlated with anti-platelet factor4 (PF4)/heparin antibodies (EIA), and heparin-dependent platelet activation (SRA).ResultsOnly HIT patient samples (20/20) caused heparin-dependent FcRIIa proteolysis, similar to what was shown by the SRA. None of the samples from the other patient groups or hospital controls caused FcRIIa proteolysis. Among nine additional samples that tested indeterminate in the SRA, FcRIIa proteolysis resolved five samples that had a positive anti-PF4/heparin EIA result; three had no FcRIIa proteolysis, and two were shown to have heparin-dependent FcRIIa proteolysisConclusionsThis study suggests that heparin-dependent FcRIIa proteolysis is at least as specific as the SRA for the diagnosis of HIT.