Does vaccination increase dogs' risk of developing immune‐mediated haemolytic anaemia?

You admitted Scout, a four-year-old female neutered English cocker spaniel, yesterday as she was jaundiced, anaemic and collapsed. Her haematocrit was 13 per cent, with prominent spherocytosis on blood smear examination. She was also positive on a saline agglutination test. You diagnosed immune-mediated haemolytic anaemia (IMHA), gave her a blood transfusion and started her on prednisolone. Her owner, Mrs Tebbut, has been on a pet health website and has read about potential adverse reactions to vaccinations. She asks you if Scout's anaemia might have been caused by her booster, which you administered four weeks ago. You wonder whether the recent vaccination could have increased Scout's risk of developing IMHA. In [dogs], does [recent vaccination] [increase the risk of immune-mediated haemolytic anaemia]? The search strategy can be viewed at https://bestbetsforvets.org/bet/599, and is also available as a supplement to this article on Vet Record‘s website at https://bvajournals.onlinelibrary.wiley.com/toc/20427670/2026/198/4 Search last performed: 18 December 2025 Of the four relevant papers identified using this search strategy, one was the previous iteration of this evidence evaluation1 and was therefore excluded. This left three relevant papers to assess. Paper 1: Vaccine-associated immune-mediated haemolytic anaemia in the dog2 Patient group: A total of 58 dogs with idiopathic IMHA that were presented at the University of Pennsylvania Veterinary Hospital between December 1992 and March 1995 were included in the study. Seventy dogs presented during the same period without IMHA, anaemia or other immune diseases were included as controls. Study type: Retrospective case-control study. Outcomes: The length of time that had elapsed between the most recent vaccination and presentation at the hospital was compared between the dogs presenting with idiopathic IMHA and the control dogs. Survival was then compared between dogs presenting with IMHA within a month of their most recent vaccination and those presenting with IMHA more than a month after their most recent vaccination. Key results: The authors of the study state that the distributions for the time from vaccination to presentation were ‘stochastically different’ between the dogs with IMHA and the control dogs. However, it was not possible to assess this as the paper lacks clarity on the statistical testing performed. In the control dogs, there was no significant correlation between the time elapsed since the most recent vaccination and presentation at the hospital. However, dogs with IMHA were more frequently presented within a month of their most recent vaccination than in subsequent months (P<0.001). Of the dogs with IMHA, 26 per cent had been vaccinated less than a month before presentation, 52 per cent had been vaccinated between one and 12 months before presentation and 22 per cent had been vaccinated between 13 and 55 months before presentation. Mortality was not significantly different between dogs that presented with IMHA within a month of their most recent vaccination and those that presented with IMHA more than a month after their most recent vaccination. Study weaknesses: Only a small number of dogs were included in the study, with fewer controls than would be required for an unmatched case-control study. The study is, therefore, likely to be underpowered. In addition, the statistical analysis is poorly described, and there are limited comparisons made with the control group. As this is a retrospective study, there is a higher risk of bias arising from inaccurate or incomplete data collection at the time of care. The control group may also not be representative of the general population. Correlation is used to infer causality between vaccination and IMHA, but there may be other reasons for the observed correlation that were not considered in this study. As such, the findings should be interpreted with caution. Paper 2: Prognostic factors for mortality and thromboembolism in canine immune-mediated haemolytic anaemia: a retrospective study of 72 dogs3 Patient group: A total of 72 dogs with idiopathic IMHA that were presented at the University of Wisconsin Veterinary Hospital between 1987 and 1995 were included in the study. Thirty-three dogs presented during the same period without IMHA were included as controls. Study type: Retrospective case-control study. Outcomes: The length of time that had elapsed between the most recent vaccination and presentation at the hospital was compared between the dogs presenting with IMHA and the control dogs. The factors associated with death in the IMHA patients were also recorded. Key results: No statistically significant difference in the distributions for the time from vaccination to presentation was found between the dogs with IMHA and the control dogs. Approximately 10 per cent of the dogs with IMHA had been vaccinated within a month of disease onset. However, the time interval from the most recent vaccination to disease onset appeared to be relatively randomly distributed when analysed graphically. Study weaknesses: Only a small number of dogs were included in the study, with fewer controls than would be required for an unmatched case-control study. The study is, therefore, likely to be underpowered. There is also limited comparison made between the dogs with IMHA and the control dogs. As this is a retrospective study, there is a higher risk of bias arising from inaccurate or incomplete data collection at the time of care. This issue is compounded by the dogs being drawn from a referral population with incomplete vaccine records. The control group may also not be representative of the general population, which could affect the interpretation of the findings. There is also a lack of data on specific vaccine exposures – different vaccines may not be equal in terms of initiating the development of IMHA. Paper 3: ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats4 Patient group: No specific patient group was studied, as this paper used data curated from multiple published sources to reach a consensus on relevant clinical guidelines. Study type: Clinical guidelines. Outcomes: This study evaluated published evidence regarding the diagnosis of IMHA and putative trigger factors (eg, vaccination). Key results: Only two papers were identified that specifically attempted to evaluate a link between vaccinations and IMHA in dogs, and these have already been assessed in this evidence evaluation. Other papers reviewed reported that vaccines could be a trigger for IMHA, but no evidence of a link between the two was found. However, data from reviewed papers were excluded if vaccination details were not specified or a diagnosis of IMHA was not certain. As such, it is possible that relevant evidence was overlooked. The outcome of the guideline generation process informing the consensus summary was that there is insufficient conclusive evidence of an association between vaccination and IMHA. Study weaknesses: No specific health intentions or target users were identified, nor were any populations identified for whom the guidelines would apply. It was also difficult to determine who was involved in the guideline development group. As no target users were identified, it was unknown whether their views were sought. Little information was provided as to how the body of evidence was assessed. A Delphi study informed the recommendations in the guidelines, but little information was provided on the process, and the outcomes were not discussed. It appears that the GRADE (grading of recommendations assessment, development and evaluation) system was used to assist in recommendation formulation, but not all domains were considered. Facilitators and barriers to the application of the guidelines and monitoring/auditing criteria for assessing guideline implementation were not discussed. Furthermore, no information was provided on how the guidelines would be updated in future. The competing interests of the authors were recorded, but there was no discussion on how these were considered. As such, bias may have been inadvertently introduced. The literature search identified only two papers that compared the vaccination history of dogs with IMHA with that of dogs that did not have the disease. Both of these studies are underpowered and subject to significant bias. Furthermore, the data were collected between 1985 and 1995. Since that time, vaccination formulations and protocols for use have changed considerably, as also may have other risk factors associated with IMHA. The consensus guidelines identified were considered to be of good quality; however, they provide no further evidence of a link between recent vaccination and IMHA. The ‘Evaluating The Evidence’ section of Vet Record aims to answer specific clinical questions using a systematic approach to identify and succinctly summarise the relevant evidence from the scientific literature. The shortcomings of this evidence are also taken into account, thereby enabling vets to incorporate the best available evidence from the literature when making clinical decisions. Please contact us at [email protected] if you have an article you would like us to consider for publication in this section. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.