Evaluation of laboratory assays for anti-platelet factor 4 antibodies after ChAdOx1 nCOV-19 vaccination
Evaluation of laboratory assays for anti-platelet factor 4 antibodies after ChAdOx1 nCOV-19 vaccination
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DOI：
10.1111/jth.15362
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发表时间：
2021-07-05
影响因子：
10.4
通讯作者：
Pavord, Sue
中科院分区：
文献类型：
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作者：
Platton, Sean;Bartlett, Andrew;Pavord, Sue
简介 ChAdOx1 nCOV-19 疫苗接种后疫苗诱导的免疫性血小板减少症和血栓形成 (VITT) 已被描述，与异常部位血栓形成、血小板减少、D-二聚体升高和高滴度免疫球蛋白-G (IgG) 类抗血小板因子 4 (PF4) 抗体相关。酶联免疫吸附测定 (ELISA) 已被证明可以检测 VITT 患者的抗 PF4，但化学发光测定不能可靠地检测它们。 ELISA 检测在诊断实验室中并未广泛使用，并且在全球范围内，很少有实验室进行血小板活化检测。方法 对英国市售的检测方法进行评估，以评估其识别疑似 VITT 患者样本中抗 PF4 抗体的能力。对来自英国各地 43 名疑似 VITT 患者的样本进行了四项 IgG 特异性 ELISA、两项多特异性 ELISA 和四项快速测定。病例在转介给英国血液学专家小组多学科团队后被识别，并分为不太可能、可能或可能的 VITT。结果和讨论 我们证明，与 ELISA 相比，HemosIL AcuStar HIT-IgG、HemosIL HIT-Ab、Diamed PaGIA 凝胶和 STic Expert 检测对 VITT 的灵敏度较差。当这些检测用于肝素诱导的血小板减少症 (HIT) 诊断时，实验室应确保明确识别可疑 VITT 的请求，以便进行 ELISA。无法证明 IgG-ELISA 在 VITT 敏感性方面优于多特异性 ELISA。没有单一 ELISA 方法检测出所有可能/可能的 VITT 病例；如果单次 ELISA 检测呈阴性，则在临床有强烈怀疑的情况下，应考虑进行第二次 ELISA 或血小板活化检测。
Introduction Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following ChAdOx1 nCOV-19 vaccine has been described, associated with unusual site thrombosis, thrombocytopenia, raised D-dimer, and high-titer immunoglobulin-G (IgG) class anti-platelet factor 4 (PF4) antibodies. Enzyme-linked immunosorbent assays (ELISA) have been shown to detect anti-PF4 in patients with VITT, but chemiluminescence assays do not reliably detect them. ELISA assays are not widely available in diagnostic laboratories, and, globally, very few laboratories perform platelet activation assays. Methods Assays that are commercially available in the United Kingdom were evaluated for their ability to identify anti-PF4 antibodies in samples from patients with suspected VITT. Four IgG-specific ELISAs, two polyspecific ELISAs, and four rapid assays were performed on samples from 43 patients with suspected VITT from across the United Kingdom. Cases were identified after referral to the UK Expert Haematology Panel multidisciplinary team and categorized into unlikely, possible, or probable VITT. Results and Discussion We demonstrated that the HemosIL AcuStar HIT-IgG, HemosIL HIT-Ab, Diamed PaGIA gel, and STic Expert assays have poor sensitivity for VITT in comparison to ELISA. Where these assays are used for heparin-induced thrombocytopenia (HIT) diagnosis, laboratories should ensure that requests for suspected VITT are clearly identified so that an ELISA is performed. No superiority of IgG-ELISAs over polyspecific ELISAs in sensitivity to VITT could be demonstrated. No single ELISA method detected all possible/probable VITT cases; if a single ELISA test is negative, a second ELISA or a platelet activation assay should be considered where there is strong clinical suspicion.