Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.
Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.
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DOI：
10.1056/nejmoa2104840
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发表时间：
2021-06-03
期刊：
影响因子：
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通讯作者：
Eichinger S
中科院分区：
文献类型：
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作者：
Greinacher A;Thiele T;Warkentin TE;Weisser K;Kyrle PA;Eichinger S
接种了编码严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）尖峰蛋白抗原的重组腺病毒载体（ChAdOx1 nCov-19，阿斯利康公司）后，出现了几例异常血栓事件和血小板减少症。我们需要更多关于这种不寻常凝血障碍发病机制的数据。
我们评估了德国和奥地利 11 名接种 ChAdOx1 nCov-19 后出现血栓或血小板减少的患者的临床和实验室特征。我们使用标准酶联免疫吸附试验检测血小板因子 4 (PF4) - 肝素抗体，并使用改良（PF4 增强）血小板活化试验检测各种反应条件下的血小板活化抗体。此次检测包括转诊调查疫苗相关血栓事件的患者血样，其中 28 人在 PF4-肝素免疫测定筛选中检测结果呈阳性。
在最初的 11 名患者中，9 人为女性，中位年龄为 36 岁（22 至 49 岁）。从接种疫苗后 5 到 16 天开始，患者出现了一次或多次血栓事件，只有一名患者例外，他出现了致命的颅内出血。在出现一种或多种血栓事件的患者中，9 人患有脑静脉血栓，3 人患有脾静脉血栓，3 人患有肺栓塞，4 人患有其他血栓；其中 6 人死亡。5 名患者出现弥散性血管内凝血。所有患者在发病前均未服用肝素。所有28名PF4-肝素抗体检测呈阳性的患者在PF4存在的情况下，血小板活化检测均呈阳性，与肝素无关。高浓度肝素、Fc 受体阻断单克隆抗体和免疫球蛋白（每毫升 10 毫克）均可抑制血小板活化。用 PF4 或 PF4-肝素亲和纯化抗体对两名患者进行的其他研究证实了 PF4 依赖性血小板活化。
接种 ChAdOx1 nCov-19 疫苗可导致罕见的由 PF4 的血小板活化抗体介导的免疫性血栓性血小板减少症，临床上可模拟自身免疫性肝素诱导的血小板减少症。(由德国研究基金会资助）。
Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)–heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4–heparin immunoassay. Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4–heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor–blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4–heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)