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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(02): 304-307
DOI: 10.1055/a-1701-2926
Letter to the Editor

Heterogeneity of Vaccine-Induced Immune Thrombotic Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination and Safety of Second Vaccination with BNT162b2

Edelgard Lindhoff-Last
1   Cardioangiology Center Bethanien Hospital, CCB Coagulation Center and CCB Coagulation Research Center, Frankfurt, Hessen, Germany
,
Linda Schoenborn
2   Department of Immunology and Transfusion Medicine, University Hospital Greifswald, Greifswald, Germany
,
Michael Piorkowski
1   Cardioangiology Center Bethanien Hospital, CCB Coagulation Center and CCB Coagulation Research Center, Frankfurt, Hessen, Germany
,
Joerg Herold
3   Department of Vascular Medicine/Angiology, Städtisches Klinikum Darmstadt, Darmstadt, Germany
,
Andreas Greinacher
2   Department of Immunology and Transfusion Medicine, University Hospital Greifswald, Greifswald, Germany
,
Jo-Ann Sheppard
4   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
,
Theodore E. Warkentin
4   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare side effect of two adenoviral vector vaccines, ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen); it is caused by platelet-activating immunoglobulin G (IgG) that recognizes platelet factor 4 (PF4), as shown by positive testing by PF4/heparin-enzyme-linked immunosorbent assay (PF4-H-ELISA) in combination with PF4-enhanced washed platelet activation assays (PF4-PAA).[1] [2] [3] Clinical presentation is heterogeneous,[4] with some patients presenting without overt thrombosis (VITT with isolated thrombocytopenia) or with severe headache.[3] [5] [6] Few data exist regarding long-term decline in PF4-dependent antibodies[7]; in addition, there is uncertainty about timing and safety of subsequent booster vaccination after an episode of VITT.

We report four cases of VITT (3 females, aged 38, 56, and 76 years; and 1 male, aged 32 years) that illustrate its diverse clinical spectrum (see [Fig. 1A–D] for details). Two patients (patients 1 and 2) had thrombocytopenia associated with both arterial and venous thromboses, while one (patient 3) had lower limb venous thrombosis without thrombocytopenia. The most unusual case was patient 4, who had thrombocytopenia together with severe, persistent headache and abdominal pain/transaminitis; however, imaging studies were negative for cerebral and abdominal thromboses, and symptoms resolved in association with early anticoagulation therapy.

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Fig. 1 (A–D) Clinical course of four patients with heterogenous presentations of vaccine-induced immune thrombotic thrombocytopenia (VITT). “Day 0” indicates the date of first vaccination with ChAdOx1nCoV-19 (AstraZeneca). The inset shows results of D-dimer (d-D; normal range < 0.5 mg/L), fibrinogen (Fib; normal range < 1.5 mg/dL), and testing for VITT antibodies. In all patients, four assays for VITT/HIT antibodies were performed: a PF4/heparin enzyme-linked immunosorbent assay (PF4-H ELISA), a chemiluminescent immunoassay for detection of HIT antibodies (CLIA, Werfen), a heparin-induced platelet activation assay (HIPA), and a PF4-enhanced washed platelet activation assay (PF4-PAA). Since none of the patients developed positive results in the HIPA-assay and the CLIA-assay, these negative results are not shown in the figure. (A) Patient 1 (female, 38 years) presented with thrombocytopenia associated with arterial and venous thromboses and the platelet count increased rapidly after two doses of IVIG. Persistent PF4-H ELISA positivity was observed. The patient declined repeat vaccination. (B) Patient 2 (female, 76 years) had severe thrombocytopenia and arterial and venous thromboses. Clinical symptoms improved during anticoagulation, without IVIG application. PF4-H ELISA and PF4-PAA declined over time. Second vaccination with BNT162b2 (day 125, Pfizer-BioNTech) was successfully applied under oral anticoagulation after VITT antibodies had become negative and vaccination was well tolerated. (C) Patient 3 (male, 32 years) presented with isolated venous thrombosis without thrombocytopenia. PF4-H ELISA antibodies persisted and successful vaccination with BNT162b2 (day 72, Pfizer-BioNTech) was performed without side effects under oral anticoagulation. (D) Patient 4 (female, 56 years) had thrombocytopenia with high D-dimer levels but venous thromboses were excluded despite severe headache and abdominal pain. She received early oral anticoagulation until day 51 after vaccination. The PF4-PAA was once positive and became quickly negative. Second vaccination with BNT162b2 (day 95, Pfizer-BioNTech) was successfully applied after stop of anticoagulation. IVIG, intravenous immunoglobulin; PF4, platelet factor 4.


Publication History

Received: 03 October 2021

Accepted: 11 November 2021

Accepted Manuscript online:
18 November 2021

Article published online:
21 January 2022

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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