Vaccine-Induced Immune Thrombotic Thrombocytopenia Caused by Zoetis PR-VAC PLUS in Pseudorabies Virus-Free Danish Purebred Pigs.

Abstract

This case report highlights a potential vaccine safety concern associated with the Pseudorabies virus (PRV) live vaccine, which warrants further investigation for comprehensive understanding. Vaccine-induced immune thrombotic thrombocytopenia (VITT), a novel syndrome of adverse events following adenovirus vector COVID-19 vaccines, was observed after vaccination with Zoetis PR-VAC PLUS. This led to a 100% morbidity and high mortality among PRV-free Danish purebred pigs from Danish Genetics Co. Clinical signs and gross presentations due to the post-thrombotic syndrome (PTS) and pulmonary embolism (PE) included (1) PE causing severe pulmonary oedema, which led to shortness of breath and respiratory failure. PTS causing (2) osteochondrosis (OCD)/leg weakness syndrome; (3) acute gastric ulcers and bleeding; (4) haemorrhagic bowel syndrome; (5) myocardial infarction or heart failure and (6) noticeable varicose veins. (7) Thrombocytopenia along with reddish or purplish spots appeared. Definitive diagnosis was based on the following as human medicine: (1) clinical signs appearing 4-42 days post-vaccination; (2) thrombocytopenia; (3) presence of thrombus in lung vessels, alveolar septa vessels, gastric vessels and small intestine, as well as other organs, as confirmed by histopathologic examination; (4) positive result from anti-heparin/PF4 ELISA testing. VITT in pigs, not previously reported, could be attributed to several factors: (1) Differences in diagnosing pigs compared to humans, especially considering that VITT associated with COVID-19 vaccines has only recently been identified. (2) Challenges in linking clinical signs such as pulmonary oedema, OCD/leg weakness, gastric ulcers and haemorrhagic bowel syndrome to thrombosis. (3) Delayed onset of clinical signs 4-42 days post-vaccination, unlike common vaccine side effects. (4) Clinical signs were varied and illogical, and ranged from mild to moderate with low mortality if there were no other complications or conditions. (5) Difficulty in diagnosing the condition due to the presence of common pathogens like PRRSV and PCV2. (6) Breeding/genetic factors can be an issue when breeders with strong immunity, who may also be highly sensitive to VITT, are selected. The potential problem of VITT might not be detected because no PR vaccine is used in Denmark.