Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

SPS commentary:

The researchers suggest these findings have several important clinical implications. Firstly, clinicians should be aware that in some patients, venous or arterial thrombosis can develop at unusual sites such as the brain or abdomen, which becomes clinically apparent ~5 to 20 days after vaccination. If such a reaction is accompanied by thrombocytopenia, it can represent an adverse effect of the preceding Covid-19 vaccination. Second, ELISA to detect PF4–heparin antibodies in patients with heparin-induced thrombocytopenia is widely available and can be used to investigate patients for potential post-vaccination thrombocytopenia or thrombosis associated with antibodies against PF4. Third, these antibodies recognize PF4 and the addition of PF4 greatly enhances their detectability in a platelet-activation assay. Since vaccination of millions of persons will be complicated by a background of thrombotic events unrelated to vaccination, a PF4-dependent ELISA or a PF4-enhanced platelet-activation assay may be used to confirm the diagnosis of vaccine-induced immune thrombotic thrombocytopenia through this novel mechanism of post-vaccination formation of platelet-activating antibodies against PF4. They stress that although treatment decisions such as administering intravenous immune globulin and starting anticoagulation do not need to await laboratory diagnosis, detection of these unusual platelet-activating antibodies will be highly relevant for case identification and future risk–benefit assessment of this and other vaccines.

This is one of two reports in the New England Journal of Medicine that provides detailed observations of patients who developed thrombotic thrombocytopenia after receiving the AstraZeneca vaccine and have speculated about a possible mechanism. The other report describes 5 Norwegian cases (age 32 to 54 years) of severe venous thrombosis and thrombocytopenia 7 to 10 days after first vaccine dose, all whom had high level of antibodies to platelet factor 4–polyanion complexes, but no previous exposure to heparin.