Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
Blood. 2021 Jul 29;138(4):350-353. doi: 10.1182/blood.2021011958.
We report 5 cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and thrombotic microangiopathy. All patients had thrombocytopenia and markedly elevated D-dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients, although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependent manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in 3 patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.
我们报告了 5 例在接触 ChAdOx1 疫苗（AZD1222，Vaxzevria）后发生的与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）相关的血栓前免疫性血小板减少症。患者在首次接种后 5 至 11 天出现症状。临床表现包括脑静脉窦血栓形成、肠系膜静脉血栓形成、动脉性脑栓塞和血栓性微血管病。所有患者均有血小板减少症和明显升高的 D-二聚体。所有患者均检测到抗血小板因子 4（PF4）自身抗体，尽管他们从未接触过肝素。患者血清中的免疫球蛋白以 AZD1222 依赖的方式与健康供体血小板结合，并被肝素抑制。在存在缓冲液或 AZD1222 的情况下，患者血清可诱导健康供体血小板聚集，并被肝素抑制。单独抗凝或联合使用依库珠单抗或静脉注射免疫球蛋白（IVIG）可使 3 例患者的病理恢复。尽管在 IVIG 后血小板增加的情况下进行了抗凝治疗，但仍有 2 例患者发生血栓栓塞事件。总之，在接种 AZD1222 后，描述了一种意外的自身免疫性血栓前性疾病。其特征为血小板减少症和抗 PF4 抗体以 AZD1222 依赖的方式与血小板结合。初步临床经验提示存在发生不常见且严重血栓栓塞事件的风险。
