Zheng Gang, Streiff Michael B, Takemoto Clifford M, Bynum Jennifer, Gelwan Elise, Jani Jayesh, Judge Danielle, Kickler Thomas S
1 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clin Appl Thromb Hemost. 2018 Jul;24(5):749-754. doi: 10.1177/1076029617721013. Epub 2017 Aug 4.
Heparin-induced thrombocytopenia (HIT) remains diagnostically challenging. Immunoassays including PF4/heparin enzyme-linked immunosorbent assay (ELISA) have high sensitivity but low specificity. Whether the heparin neutralization assay (HNA) improves the diagnostic accuracy of the PF4/heparin ELISA for HIT is uncertain. In this study, to assess its clinical utility and evaluate whether it improves the diagnostic accuracy for HIT, we implemented HNA in conjunction with PF4/heparin ELISA over a 1-year period. A total of 1194 patient samples were submitted to the laboratory for testing from December 2015 to November 2016. Heparin neutralization assay alone is a poor predictor for HIT, but it has high negative predictive value (NPV): Cases with %inhibition <70% are always negative for serotonin release assay. It improves the diagnostic positive predictive value (PPV) of ELISA without compromising sensitivity: ELISA optical density (OD) ≥1.4 alone has a sensitivity of 88% (14/16) and a PPV of 61% (14/23); with HNA %inhibition ≥70%, the sensitivity remains 88% (14/16) and PPV is 82% (14/17). 4Ts score correlates with ELISA OD and predicts HIT; the predictive accuracy of 4Ts score is further improved by HNA. Interestingly, HNA %inhibition of <70% correlates with low 4Ts scores. Based on its high NPV, HNA has the potential to facilitate more timely and accurate HIT diagnosis.
肝素诱导的血小板减少症(HIT)的诊断仍然具有挑战性。包括PF4/肝素酶联免疫吸附测定(ELISA)在内的免疫测定具有高灵敏度但低特异性。肝素中和试验(HNA)是否能提高PF4/肝素ELISA对HIT的诊断准确性尚不确定。在本研究中,为了评估其临床效用并评估它是否能提高HIT的诊断准确性,我们在1年的时间里将HNA与PF4/肝素ELISA联合应用。2015年12月至2016年11月期间,共有1194份患者样本被送至实验室进行检测。单独的肝素中和试验对HIT的预测能力较差,但它具有高阴性预测值(NPV):抑制率<70%的病例血清素释放试验总是阴性。它在不影响灵敏度的情况下提高了ELISA的诊断阳性预测值(PPV):单独ELISA光密度(OD)≥1.4时,灵敏度为88%(14/16),PPV为61%(14/23);当HNA抑制率≥70%时,灵敏度仍为88%(14/16),PPV为82%(14/17)。4Ts评分与ELISA OD相关并可预测HIT;HNA进一步提高了4Ts评分的预测准确性。有趣的是,HNA抑制率<70%与低4Ts评分相关。基于其高NPV,HNA有潜力促进更及时、准确的HIT诊断。