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Case Reports
. 2021 Jun 3;384(22):2124-2130.
doi: 10.1056/NEJMoa2104882. Epub 2021 Apr 9.

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

Nina H Schultz  1 , Ingvild H Sørvoll  1 , Annika E Michelsen  1 , Ludvig A Munthe  1 , Fridtjof Lund-Johansen  1 , Maria T Ahlen  1 , Markus Wiedmann  1 , Anne-Hege Aamodt  1 , Thor H Skattør  1 , Geir E Tjønnfjord  1 , Pål A Holme  1
Affiliations
Case Reports

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

Nina H Schultz et al. N Engl J Med. .

Abstract

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.

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Figures

Figure 1
Figure 1. Platelet Count Responses to Treatment.
The vertical dashed line indicates the time at which the results of platelet factor 4 (PF4)–polyanion antibody tests were known. IVIG denotes intravenous immune globulin.
Figure 2
Figure 2. IgG PF4–Polyanion Detection in Serum.
IgG PF4–polyanion antibodies in serum from the patients were measured by enzyme-linked immunosorbent assay. Serum from all the patients showed strong reactivity that was efficiently inhibited (>97%) by the addition of a saturating dose of heparin (100 IU per milliliter). Samples were run in duplicate. A mean optical density of 0.4 or higher indicates the presence of antibodies.
Figure 3
Figure 3. Platelet-Aggregating Potential of Serum in Functional Testing.
Aggregation of donor platelets after incubation with serum from the patients was measured by whole-blood impedance aggregometry. The measurements were performed in the presence of low or high heparin concentrations and in the absence of added heparin (saline). Serum from a healthy donor and serum from a patient with typical heparin-induced thrombocytopenia (HIT) are also shown. The red and blue lines represent duplicate measurements. AU denotes arbitrary units, and AUC the area under the curve.
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