Persistence of Ad26.COV2.S-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies.
Persistence of Ad26.COV2.S-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies.
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DOI：
10.1002/ajh.26488
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发表时间：
2022-05
影响因子：
12.8
通讯作者：
Padmanabhan A
中科院分区：
文献类型：
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作者：
Kanack AJ;Singh B;George G;Gundabolu K;Koepsell SA;Abou-Ismail MY;Moser KA;Smock KJ;Green D;Major A;Chan CW;Wool GD;Reding M;Ashrani AA;Bayas A;Grill DE;Padmanabhan A
接种COVID-19疫苗的个体极少数会产生抗血小板因子4（PF 4）抗体，导致血小板减少症和血栓性并发症，这是一种被称为疫苗诱导的免疫性血栓性血小板减少症（VITT）的综合征。目前，关于Ad26.COV2.S疫苗接种后引起VITT的抗PF 4抗体的特征和持续性的信息有限，可用的诊断检测无法区分Ad26.COV2.S和ChAdOx 1 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）和自发性HIT。在这里，我们证明，虽然Ad26.COV2.S相关的VITT患者在PF 4-聚阴离子酶联免疫吸附试验（ELISA）中一致呈强阳性;但他们在5-羟色胺释放试验（SRA）中经常呈阴性。使用PF 4而非肝素处理的血小板的PF 4依赖性p选择素表达试验（PEA）一致诊断为Ad26.COV2.S相关VITT。大多数Ad26.COV2.S相关VITT抗体在PF 4-聚阴离子ELISA中持续>5个月，而PEA更早变为阴性。2例患者在急性发作后6个月出现其他原因不明的轻度持续性血小板减少症（140 - 150 x 103/µL）。从流行病学的角度来看，将VITT与自发性HIT（另一种在没有肝素暴露的情况下发生的实体）和HIT区分开来很重要，但目前可用的PF 4-聚阴离子ELISA和功能测定是非特异性的，可检测所有三种情况。在这里，我们报告了一种新的未复合的PF 4 ELISA特异性区分了继发于Ad26.COV2.S和ChAdOx 1 nCoV-19的VITT与自发性HIT、HIT和常见的HIT-疑似患者（PF 4/聚阴离子ELISA阳性，但在功能测定中为阴性）。总之，Ad26.COV2.S相关VITT抗体具有持久性，未复合的PF 4 ELISA似乎对VITT诊断具有灵敏度和特异性。
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 103/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.
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DOI：
10.1056/nejmoa2104840
发表时间：
2021-06-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Greinacher A;Thiele T;Warkentin TE;Weisser K;Kyrle PA;Eichinger S
通讯作者：
Eichinger S
影响因子：
2.9
作者：
Irani, Mehraboon;Siegal, Eric;Padmanabhan, Anand
通讯作者：
Padmanabhan, Anand
影响因子：
1.5
作者：
Major, Ajay;Carll, Timothy;Cohen, Kenneth S.
通讯作者：
Cohen, Kenneth S.
影响因子：
158.5
作者：
Warkentin, TE;Kelton, JG
通讯作者：
Kelton, JG
影响因子：
7.5
作者：
Rodriguez EVC;Bouazza FZ;Dauby N;Mullier F;d'Otreppe S;Jissendi Tchofo P;Bartiaux M;Sirjacques C;Roman A;Hermans C;Cliquennois M
通讯作者：
Cliquennois M