Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Medicine, University of Colorado, Aurora, Colorado, USA.
Am J Hematol. 2022 May;97(5):519-526. doi: 10.1002/ajh.26488. Epub 2022 Feb 21.
Rare cases of COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.S vaccination is limited, and available diagnostic assays fail to differentiate Ad26.COV2.S and ChAdOx1 nCoV-19-associated VITT from similar clinical disorders, namely heparin-induced thrombocytopenia (HIT) and spontaneous HIT. Here we demonstrate that while Ad26.COV2.S-associated VITT patients are uniformly strongly positive in PF4-polyanion enzyme-linked immunosorbent assays (ELISAs); they are frequently negative in the serotonin release assay (SRA). The PF4-dependent p-selectin expression assay (PEA) that uses platelets treated with PF4 rather than heparin consistently diagnosed Ad26.COV2.S-associated VITT. Most Ad26.COV2.S-associated VITT antibodies persisted for >5 months in PF4-polyanion ELISAs, while the PEA became negative earlier. Two patients had otherwise unexplained mild persistent thrombocytopenia (140-150 x 10 /µL) 6 months after acute presentation. From an epidemiological perspective, differentiating VITT from spontaneous HIT, another entity that develops in the absence of proximate heparin exposure, and HIT is important, but currently available PF4-polyanion ELISAs and functional assay are non-specific and detect all three conditions. Here, we report that a novel un-complexed PF4 ELISA specifically differentiates VITT, secondary to both Ad26.COV2.S and ChAdOx1 nCoV-19, from both spontaneous HIT, HIT and commonly-encountered HIT-suspected patients who are PF4/polyanion ELISA-positive but negative in functional assays. In summary, Ad26.COV2.S-associated VITT antibodies are persistent, and the un-complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.
在接种 COVID-19 疫苗的罕见病例中，会产生抗血小板因子 4（PF4）抗体，导致血小板减少和血栓并发症，这种综合征被称为疫苗诱导的免疫性血栓性血小板减少症（VITT）。目前，关于 Ad26.COV2.S 疫苗接种后引起 VITT 的抗 PF4 抗体的特征和持久性的信息有限，并且现有的诊断检测无法将 Ad26.COV2.S 和 ChAdOx1 nCoV-19 相关的 VITT 与类似的临床疾病（即肝素诱导的血小板减少症 [HIT]）区分开来。在这里，我们证明虽然 Ad26.COV2.S 相关的 VITT 患者在 PF4-多阴离子酶联免疫吸附测定（ELISA）中均呈强阳性；但他们在血清素释放测定（SRA）中经常呈阴性。使用经 PF4 而非肝素处理的血小板进行的 PF4 依赖性 p-选择素表达测定（PEA）一致诊断出 Ad26.COV2.S 相关的 VITT。大多数 Ad26.COV2.S 相关的 VITT 抗体在 PF4-多阴离子 ELISA 中持续存在>5 个月，而 PEA 更早呈阴性。两名患者在急性发作后 6 个月仍有其他不明原因的轻度持续性血小板减少症（140-150×10 /µL）。从流行病学的角度来看，区分 VITT 与自发性 HIT（另一种在没有接触肝素的情况下发生的实体）和 HIT 很重要，但目前可用的 PF4-多阴离子 ELISA 和功能检测是非特异性的，可检测到所有三种情况。在这里，我们报告了一种新的未复合 PF4 ELISA，可特异性区分 VITT，继发于 Ad26.COV2.S 和 ChAdOx1 nCoV-19，以及自发性 HIT、HIT 和常见的 HIT 疑似患者，这些患者在功能检测中为 PF4/多阴离子 ELISA 阳性，但呈阴性。总之，Ad26.COV2.S 相关的 VITT 抗体是持久的，未复合的 PF4 ELISA 似乎对 VITT 诊断既敏感又特异。
