Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac

doi:10.1007/s11684-023-1054-2

Front. Med.

2024, Vol. 18

Issue (4) : 744-751 https://doi.org/10.1007/s11684-023-1054-2

Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac

Zhangbiao Long¹, Suyu Jiang², Honglei Xin², Lu Zhang², Ruinan Lu³, Fengqi Liu³, Yong Xu⁴, Linv Wang⁵, Jun Wang⁶, Xuezhong Zhang⁷, Hui Liao⁸, Jinning Shi⁹, Xue Yan⁹, Xiang Zhu¹⁰, Ruonan Shao², Zijian Li², Yilin Zhu², Han Yan², Jiao Wu², Chao Fang¹¹(

), Xiaodong Xi¹²(

), Xiaofeng Shi²(

)

¹. Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
². Department of Hematology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210003, China
³. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
⁴. Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
⁵. Department of Hematology, The Affiliated Hospital of Nanjing University of Chinese Medicine, The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210009, China
⁶. Department of Hematology, Zhongda Hospital of Southeast University, Nanjing 210044, China
⁷. Department of Hematology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
⁸. Department of Hematology, The Air Force Hospital of Eastern Theater command, Nanjing 210016, China
⁹. Department of Hematology, Jiangning Hospital Affiliated of Nanjing Medical University, Nanjing 211199, China
¹⁰. Department of Hematology, Nanjing Hospital of Chinese Medicine, Nanjing 210006, China
¹¹. Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China
¹². Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

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Abstract

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors’ knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.

Keywords thrombotic thrombocytopenia purpura (TTP) corona virus disease 2019 (COVID-19) CoronaVac acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine

Corresponding Author(s): Chao Fang,Xiaodong Xi,Xiaofeng Shi

Just Accepted Date: 16 May 2024 Online First Date: 02 July 2024 Issue Date: 30 August 2024

Cite this article:

Zhangbiao Long,Suyu Jiang,Honglei Xin, et al. Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac[J]. Front. Med., 2024, 18(4): 744-751.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-023-1054-2
https://academic.hep.com.cn/fmd/EN/Y2024/V18/I4/744

Fig.1 Case 1. (A) Purpura in the arm skin. (B) Schistocytes on peripheral blood smear. (C) Comparison of plasma exchange product (top) and normal plasma (bottom) following the first (i), second (ii), and third (iii) sessions of plasma exchange. (D) Comparison of urine before (i) and after (ii) plasma exchange. (E–G) Change in blood cell count, coagulation index, hemolytic test, and renal function over the course of disease progression. Vaccine was administered on day 0, and treatment started on day 15. Green and red triangles indicate the time of plasma exchange and rituximab treatment, respectively. Blue pentagon indicates the administration of glucocorticoid. (E) Platelet, hemoglobin (Hb), D-dimer, and fibrinogen degradation product (FDP). (F) Lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), direct bilirubin, and indirect bilirubin. (G) Uric acid (UA) and creatine (Cr).

Fig.2 Case 2. Change in blood cell count, coagulation index, hemolytic test, and renal function over the course of disease progression. Vaccine was administered on day 0, and treatment started on day 16. Green and red triangles indicate the time of plasma exchange and fresh frozen plasma transfusion, respectively. Blue pentagon indicates the administration of glucocorticoid. Yellow box indicates the administration of hemodialysis. (A) Platelet, hemoglobin (Hb), D-dimer, and fibrinogen degradation product (FDP). (B) Lactate dehydrogenase (LDH), direct bilirubin, and indirect bilirubin. (C) Uric acid (UA) and creatine (Cr).

Tab.1 Patients with TTP from 14 hospitals in Nanjing area in recent years

Fig.3 Time axis and important events.

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