Department of Medicine, Michael G. DeGroote School of Medicine.
Department of Biochemistry and Biomedical Sciences, and.
Blood Adv. 2022 Jul 26;6(14):4228-4235. doi: 10.1182/bloodadvances.2022007766.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious adverse syndrome occurring 5 to 30 days after adenoviral vector COVID-19 vaccination. Therefore, a practical evaluation of clinical assessments and laboratory testing for VITT is needed to prevent significant adverse outcomes as the global use of adenoviral vector vaccines continues. We received the clinical information and blood samples of 156 patients in Canada with a suspected diagnosis of VITT between April and July 2021. The performance characteristics of various diagnostic laboratory tests were evaluated against the platelet factor 4 (PF4)-14C-serotonin release assay (SRA) including a commercial anti-PF4/heparin immunoglobulin G (IgG)/IgA/IgM enzyme immunoassay (EIA, PF4 Enhanced; Immucor), in-house IgG-specific anti-PF4 and anti-PF4/heparin-EIAs, the standard SRA, and the PF4/heparin-SRA. Of those, 43 (27.6%) had serologically confirmed VITT-positive based on a positive PF4-SRA result and 113 (72.4%) were VITT-negative. The commercial anti-PF4/heparin EIA, the in-house anti-PF4-EIA, and anti-PF4/heparin-EIA were positive for all 43 VITT-confirmed samples (100% sensitivity) with a few false-positive results (mean specificity, 95.6%). These immunoassays had specificities of 95.6% (95% confidence interval [CI], 90.0-98.6), 96.5% (95% CI, 91.2-99.0), and 97.4% (95% CI, 92.4-99.5), respectively. Functional tests, including the standard SRA and PF4/heparin-SRA, had high specificities (100%), but poor sensitivities for VITT (16.7% [95% CI, 7.0-31.4]; and 46.2% [95% CI, 26.6-66.6], respectively). These findings suggest EIA assays that can directly detect antibodies to PF4 or PF4/heparin have excellent performance characteristics and may be useful as a diagnostic test if the F4-SRA is unavailable.
疫苗诱导的免疫性血栓性血小板减少症（VITT）是一种罕见但严重的不良综合征，发生在腺病毒载体 COVID-19 疫苗接种后 5 至 30 天。因此，随着腺病毒载体疫苗在全球的使用不断增加，需要对 VITT 的临床评估和实验室检测进行实际评估，以防止出现重大不良后果。我们收到了 2021 年 4 月至 7 月期间加拿大 156 名疑似 VITT 患者的临床信息和血样。评估了各种诊断性实验室检测的性能特征，包括血小板因子 4（PF4）-14C- 血清素释放测定（SRA），包括商业性抗 PF4/肝素免疫球蛋白 G（IgG）/IgA/IgM 酶联免疫吸附试验（EIA，PF4 增强；Immucor）、内源性 IgG 特异性抗 PF4 和抗 PF4/肝素-EIA、标准 SRA 和 PF4/肝素-SRA。其中，43 例（27.6%）根据 PF4-SRA 阳性结果被确认为血清学阳性 VITT，113 例（72.4%）为 VITT 阴性。商业性抗 PF4/肝素 EIA、内源性抗 PF4-EIA 和抗 PF4/肝素-EIA 对所有 43 例 VITT 确诊样本均为阳性（敏感性 100%），但有少数假阳性结果（平均特异性 95.6%）。这些免疫测定的特异性分别为 95.6%（95%CI，90.0-98.6）、96.5%（95%CI，91.2-99.0）和 97.4%（95%CI，92.4-99.5）。功能试验，包括标准 SRA 和 PF4/肝素-SRA，特异性高（100%），但对 VITT 的敏感性低（分别为 16.7%[95%CI，7.0-31.4%]和 46.2%[95%CI，26.6-66.6%]）。这些发现表明，可直接检测抗 PF4 或 PF4/肝素抗体的 EIA 检测具有优异的性能特征，如果无法进行 F4-SRA 检测，这些检测可能可作为诊断性检测。
