Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

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.

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. 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. 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.