AstraZeneca coronavirus vaccine rarely causes immune thrombotic thrombocytopenia

1. ChAdOx1 nCov-19 vaccine has been linked to immune thrombotic thrombocytopenia in patients after vaccination resembling autoimmune heparin-induced thrombocytopenia.

2. Treatment options for this disorder include high-dose intravenous immune globulin and anticoagulants approved for the treatment of heparin-induced thrombocytopenia.

Evidence Rating Level: 4 (Below Average)   

Study Rundown: Vaccines are the first-line defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). At the beginning of April 2021, more than 82 million vaccine doses had been administered in the European Union with one-quarter of the vaccine recipients in Germany receiving the ChAdOx1 nCov-19 vaccine. Beginning in late February 2021, cases of thrombotic events in combination with thrombocytopenia were observed in patients who have received the ChAdOx1 nCov-19 vaccine. As such, this case series study presented the data of the thrombotic events related to the vaccine. Immune thrombotic thrombocytopenia was reported in 11 patients after vaccination with the ChAdOx1 nCov-19 vaccine. Besides one patient who suffered a fatal intracranial hemorrhage, all other patients presented with one or more thrombotic events. The serum of these patients showed strong reactivity to platelet factor 4 (PF4)-heparin antibodies, a test used in the diagnosis of heparin-induced thrombocytopenia (HIT). However, none of the patients had prior exposure to heparin. The study suggested this immune disorder is driven by platelet-activating antibodies against PF4, which may occur after free DNA complexes with PF4 forming anti-PF4 antibodies. They suggest naming this condition vaccine-induced immune thrombotic thrombocytopenia (VITT). A strength of this study is in the formulation of a potential therapeutic framework for VITT, namely using non-heparin anticoagulants when treating these patients. The study was limited by a small sample size of 11 patients. Nonetheless, the study’s results are significant as it provides data on a potentially serious adverse event after ChAdOx1 nCov-19 vaccine administration.

Click to read the study in NEJM

Relevant Reading: Bilateral superior ophthalmic vein thrombosis, ischaemic stroke, and immune thrombocytopenia after ChAdOx1 nCoV-19 vaccination

In-Depth [case series]: The study provided a case series study of patients who developed thrombotic events in combination with thrombocytopenia in Germany and Austria after the administration of the ChAdOx1 nCov-19 vaccine. The index case occurred in mid-February 2021 where a patient was admitted for fever and epigastric discomfort. By March 15, 2021, 11 patients from Germany and Austria presented 5 to 16 days, after vaccination, with either thrombosis or thrombocytopenia. This case series study aimed to investigate the clinical and laboratory factors of these patients. The median age for the patients was 36 years (range, 22 to 49 years), and nine of the 11 patients were women. Overall, there were nine events of cerebral venous thrombosis, three events of splanchnic-vein thrombosis, three events of pulmonary embolism, and one event of fatal intracranial hemorrhage. From the then patients with one or more thromboses, six patients died. The serum of nine patients showed strong reactivity on PF4-heparin enzyme-linked immunosorbent assay (ELISA) with an optical density greater than 3.00 units (reference value, <0.50). Using platelets derived from healthy donor whole blood, a platelet activation assay was performing using four of the serum samples from the thrombotic patients. The platelet activation assay showed increased reactivity in the presence of PF4, independent of heparin, and inhibition with low molecular weight heparin or intravenous immune globulin. These results were validated in 24 patients who tested positive with PF4-heparin ELISA after vaccination. Lastly, the serum of two of the original 11 patients was affinity-purified for antibodies using immobilized PF4 or immobilized PF4-heparin. In the presence of PF4, the purified antibodies strongly activated platelets, however the same was not found in the presence of heparin alone. Overall, the ChAdOx1 nCov-19 vaccine has the potential to result in immune thrombotic thrombocytopenia that resembles autoimmune heparin-induced thrombocytopenia. Based on the case study, the incidence of serious adverse events was rare; however, health care providers should be cautious in screening patients administered the vaccine for the thrombotic adverse event.

Image: PD

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