Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Institute of Bioinformatics, Universitätsmedizin Greifswald, Greifswald, Germany.
J Thromb Haemost. 2022 Nov;20(11):2579-2586. doi: 10.1111/jth.15862. Epub 2022 Sep 4.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic, heparin-induced thrombocytopenia (HIT)-mimicking, adverse reaction caused by platelet-activating anti-platelet factor 4 (PF4) antibodies that occurs rarely after adenovirus vector-based COVID-19 vaccination. Strength of PF4-dependent enzyme immunoassay (EIA) reactivity-judged by optical density (OD) measurements-strongly predicts platelet-activating properties of HIT antibodies in a functional test. Whether a similar relationship holds for VITT antibodies is unknown.
To evaluate probability for positive platelet activation testing for VITT antibodies based upon EIA OD reactivity; and to investigate simple approaches to minimize false-negative platelet activation testing for VITT.
All samples referred for VITT testing were systematically evaluated by semiquantitative in-house PF4/heparin-EIA (OD readings) and PF4-induced platelet activation (PIPA) testing within a cohort study. EIA-positive sera testing PIPA-negative were retested following 1/4 to 1/10 dilution. Logistic regression was performed to predict the probability of a positive PIPA per magnitude of EIA reactivity.
Greater EIA ODs in sera from patients with suspected VITT correlated strongly with greater likelihood of PIPA reactivity. Of 61 sera (with OD values >1.0) testing negative in the PIPA, a high proportion (27/61, 44.3%) became PIPA positive when tested at 1/4 to 1/10 dilution.
VITT serology resembles HIT in that greater EIA OD reactivity predicts higher probability of positive testing for platelet-activating antibodies. Unlike the situation with HIT antibodies, however, diluting putative VITT serum increases probability of a positive platelet activation assay, suggesting that optimal complex formation depends on the stoichiometric ratio of PF4 and anti-PF4 VITT antibodies.
疫苗诱导的免疫性血栓性血小板减少症（VITT）是一种罕见的由血小板激活抗血小板因子 4（PF4）抗体引起的促血栓形成、肝素诱导的血小板减少症（HIT）样不良反应，这种不良反应发生在基于腺病毒载体的 COVID-19 疫苗接种后。通过光密度（OD）测量判断 PF4 依赖性酶免疫分析（EIA）反应性的强度强烈预测了功能试验中 HIT 抗体的血小板激活特性。对于 VITT 抗体是否存在类似的关系尚不清楚。
评估基于 EIA OD 反应性预测 VITT 抗体阳性血小板激活检测的可能性；并探讨最小化 VITT 抗体阳性血小板激活检测假阴性的简单方法。
在一项队列研究中，对所有疑似 VITT 检测的样本进行了系统评估，包括半定量 PF4/肝素-EIA（OD 读数）和 PF4 诱导的血小板激活（PIPA）检测。对 EIA 阳性而 PIPA 阴性的血清进行 1/4 至 1/10 稀释后再检测。进行逻辑回归以预测每个 EIA 反应性量级的 PIPA 阳性概率。
来自疑似 VITT 患者的血清中 EIA OD 值越高，与 PIPA 反应性越高的相关性越强。在 61 份（OD 值>1.0）PIPA 检测阴性的血清中，有很大一部分（27/61，44.3%）在 1/4 至 1/10 稀释后成为 PIPA 阳性。
VITT 血清学与 HIT 相似，即 EIA OD 值越高，预测血小板激活抗体阳性检测的可能性越高。然而，与 HIT 抗体不同的是，稀释疑似 VITT 血清会增加阳性血小板激活检测的可能性，这表明最佳的复杂形成取决于 PF4 和抗 PF4 VITT 抗体的化学计量比。
