Investigation and systematic review of temporal associations between vaccination and onset of immune-mediated hemolytic anemia or thrombocytopenia in dogs

Abstract Background Vaccination is implicated in development of human immune-mediated diseases, but studies in dogs yielded conflicting results for immune-mediated hemolytic anemia (IMHA) and thrombocytopenia (ITP). Hypothesis/Objectives To investigate temporal relationships between onset of IMHA or ITP and vaccination in dogs. Animals Client-owned dogs with nonassociative IMHA (n = 295) and ITP (n = 163) at 4 referral hospitals, alongside control dogs (n = 1180 for IMHA, 652 for ITP) presented contemporaneously. Methods Multicenter retrospective case–control study, with meta-analysis of published studies. Proportions vaccinated ≤ 30 days before disease onset were compared to controls, along with times since last vaccine. Results Proportion of dogs vaccinated ≤ 30 days of disease onset was significantly higher in the IMHA group (35/295, 11.9%) compared with controls (72/1180, 6.1%; P = .0015). Dogs with IMHA vaccinated ≤ 30 days of disease onset were more likely to have received a L2 vaccine (Leptospira serovars Canicola and Icterohemorrhagiae) in their last dose than those vaccinated 30 days before onset (P = .04). Meta-analysis indicated dogs with IMHA were 2.48 times (95% CI, 1.69-3.63) more likely to have been vaccinated in the past month than controls, but with high heterogeneity across this and 2 other studies. There was no difference in proportion of ITP dogs and controls vaccinated ≤ 30 days of disease onset, and meta-analysis with 1 other study showed no temporal association, though both analyses were likely underpowered. Conclusions and clinical importance These results support a possible temporal association between vaccination and onset of IMHA in dogs. Our results do not establish a causal relationship between vaccination and IMHA.