Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
Vaccine. 2024 Nov 14;42(25):126175. doi: 10.1016/j.vaccine.2024.126175. Epub 2024 Aug 5.
The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil.
From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays.
630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination.
Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.
Ad26.COV2·S（杨森/强生）COVID-19 疫苗与疫苗诱导的免疫性血小板减少和血栓形成（VITT）很少有关联。我们研究了巴西里约热内卢接种 Ad26.COV2·S 后抗 PF4 抗体阳性、血小板减少、D-二聚体升高、血浆血栓炎症标志物和血小板功能测定的发生率。
2021 年 7 月至 9 月，在接种疫苗前、接种后 1 周和 3 周评估参与者。每次就诊时测量血小板计数和 D-二聚体，第 3 周测量抗 PF4。抗 PF4 阳性提示回顾性检测第 0 周的样本。对新发血小板减少症或 D-二聚体升高、抗 PF4 阳性且无实验室异常的 38 名匹配对照者进行血浆 p-选择素、组织因子和功能血小板激活测定。
共纳入 630 人；女性 306 人（48.57%），中位年龄 28 岁。第 1 周或第 3 周有≥1 项实验室异常者 42 人（6.67%）。第 3 周有 5 人（0.79%）血小板减少症，31 人（4.91%）D-二聚体升高，9 人（1.57%）抗 PF4 阳性。有实验室异常的患者和对照组血浆 p-选择素和组织因子略有增加。10 名有实验室异常的患者表面 p-选择素表达增加，并进一步评估了其依赖 FcγRIIa 激活血小板的能力。其中 2 人被高浓度肝素部分抑制，用 IV.3 抗体阻断 FcγRII。接种前获得的血浆产生了类似的结果，提示与接种无关。
接种 Ad26.COV2·S 疫苗导致低滴度抗 PF4 抗体阳性、D-二聚体升高和轻度血小板减少的频率非常低，且无相关的血栓炎症标志物和血小板激活的临床相关增加。
