A prospective, blinded study of a PF4-dependent assay for HIT diagnosis
A prospective, blinded study of a PF4-dependent assay for HIT diagnosis
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DOI：
10.1182/blood.2020008195
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发表时间：
2021-02-25
期刊：
影响因子：
20.3
通讯作者：
Padmanabhan, Anand
中科院分区：
文献类型：
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作者：
Bannow, Bethany Samuelson;Warad, Deepti M.;Padmanabhan, Anand
肝素诱导的血小板减少症(HIT)是一种危及生命的、血栓前状态、抗体介导的疾病。为了最大限度地提高康复的可能性，早期准确的诊断至关重要。广泛使用的HIT检测方法，如血小板第4因子(PF4)、肝素酶联免疫吸附试验(ELISA)缺乏特异性，而金标准的碳14标记的5-羟色胺释放试验(SRA)只能通过参考实验室获得，因此在早期患者管理中的价值有限。最近的研究表明，致病HIT抗体选择性地激活经PF4处理的血小板，而且一种技术更简单的方法-PF4依赖的P-选择素表达分析(PEA)可能为快速和确凿的结果提供一种选择。根据结合4TS评分和HIT-ELISA结果的预定义标准，连续409名疑似HIT的成年人被归类为疾病阳性、阴性或不确定。被认为HIT不确定的患者在初步分析中被认为疾病阴性，在敏感性分析中被认为疾病阳性。使用受试者操作特征曲线统计比较PEA和SRA识别被判定为HIT的患者的能力。使用这些预先定义的标准，PEA的诊断准确率很高(曲线下面积[AUC]，0.94；95%可信区间[CI]，0.87~1.0)，与SRA相似(AUC，0.91；95%CI，0.82~1.0)。在敏感性分析中，PEA和SRA的AUC分别为0.88(95%CI，0.78~0.98)和0.86(95%CI，0.77~0.96)。PEA是一种技术简单的非放射性检测方法，与SRA相比，它使用的血小板类似于SRA的20倍，对HIT的诊断具有很高的准确性。PEA的广泛应用可能有助于及时和更有效地处理疑似HIT患者。
Heparin-induced thrombocytopenia (HIT) is a life-threatening, prothrombotic, antibodymediated disorder. To maximize the likelihood of recovery, early and accurate diagnosis is critical. Widely available HIT assays, such as the platelet factor 4 (PF4) heparin enzymelinked immunosorbent assay (ELISA) lack specificity, and the gold-standard carbon 14-labeled serotonin release assay (SRA) is of limited value for early patient management because it is available only through reference laboratories. Recent studies have demonstrated that pathogenic HIT antibodies selectively activate PF4-treated platelets and that a technically simpler assay, the PF4-dependent P-selectin expression assay (PEA), may provide an option for rapid and conclusive results. Based upon predefined criteria that combined 4Ts scores and HIT ELISA results, 409 consecutive adults suspected of having HIT were classified as disease positive, negative, or indeterminate. Patients deemed HIT indeterminate were considered disease negative in the primary analysis and disease positive in a sensitivity analysis. The ability of PEA and SRA to identify patients judged to have HIT was compared using receiver operating characteristic curve statistics. Using these predefined criteria, the diagnostic accuracy of PEA was high (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.87-1.0) and similar to that of SRA (AUC, 0.91; 95% CI, 0.82-1.0). In sensitivity analysis, the AUCs of PEA and SRA were also similar at 0.88 (95% CI, 0.78-0.98) and 0.86 (95% CI, 0.77-0.96), respectively. The PEA, a technically simple nonradioactive assay that uses similar to 20-fold fewer platelets compared with the SRA, had high accuracy for diagnosing HIT. Widespread use of the PEA may facilitate timely and more effective management of patients with suspected HIT.