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ChAdOx1 nCov-19疫苗接种后可导致罕见的血栓性血小板减少症
(来源:科学网-小柯机器人 )


德国格拉夫斯瓦尓德免疫与输血医学研究所Andreas Greinacher团队研究了ChAdOx1 nCov-19疫苗接种后的血栓性血小板减少症。2021年4月9日,《新英格兰医学杂志》发表了该成果。

近期,在使用编码SARS-CoV-2刺突蛋白抗原的重组腺病毒载体(ChAdOx1 nCov-19,阿斯利康)接种后,接种者出现了一些不寻常的血栓性事件和血小板减少症。关于这种不寻常凝血障碍的发病机制尚不明确。

研究组评估了德国和奥地利11例接种ChAdOx1 nCov-19疫苗后出现血栓形成或血小板减少的患者的临床和实验室特征。研究组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。该试验样本来自有疫苗相关血栓事件调查的血液样本的患者,其中28例在筛选PF4-肝素免疫分析中呈阳性。

11名患者中9名为女性,中位年龄为36岁。接种后5~16天,除1例出现致命性颅内出血外,其余患者均发生一次或多次血栓形成。在有一个或多个血栓事件的患者中,9例有脑静脉血栓形成,3例有内脏静脉血栓形成,3例有肺栓塞,4例有其他血栓形成,其中6例死亡。5例出现弥散性血管内凝血。症状发作前所有患者均未接受肝素治疗。

所有28名抗PF4-肝素抗体检测呈阳性的患者,在不依赖于肝素PF4存在下,血小板活化试验呈阳性。高水平肝素、Fc受体阻断单克隆抗体和免疫球蛋白(10 mg/ml)抑制血小板活化。在2例患者中使用PF4或PF4-肝素亲和纯化抗体的其他研究证实了PF4依赖的血小板激活。

研究结果表明,接种ChAdOx1 nCov-19可导致罕见的免疫性血栓性血小板减少症。



附:英文原文

Title: Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

Author: Andreas Greinacher, M.D.,, Thomas Thiele, M.D.,, Theodore E. Warkentin, M.D.,, Karin Weisser, Ph.D.,, Paul A. Kyrle, M.D.,, and Sabine Eichinger, M.D.

Issue&Volume: 2021-04-09

Abstract:

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

DOI: 10.1056/NEJMoa2104840

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2104840

 

期刊信息

The New England Journal of Medicine《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/


时间: 2021 年 08 月 06 日
           
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