Hyperbilirubinemia and neurologic signs in dogs with non-associative immune-mediated hemolytic anemia: 81 cases (2015-2024)

Background: Bilirubin encephalopathy is a poorly recognized complication in dogs with immune-mediated hemolytic-anemia (IMHA).

Hypothesis/Objectives: Assess serial trends of hyperbilirubinemia and the association between bilirubin concentrations and neurologic signs in dogs with IMHA.

Animals: Eighty one dogs with non-associative IMHA and hyperbilirubinemia.

Methods: Multicenter retrospective cohort study. The signalment, clinical signs, clinicopathological data, treatment, and outcome were evaluated. Bilirubin concentrations were recorded at the baseline, peak, initial decrease, and normalization. Univariable logistic regression was used to determine the association between neurologic signs and hyperbilirubinemia.

Results: The median bilirubin concentrations at the baseline, peak, and initial decrease were 2.5 (IQR, 1.4–4.8), 3.7 (IQR, 1.8–24.2), and 1.1 mg/dL (IQR, 0.5–4.3; 43, 64, and 19 μmol/L), respectively. Twenty percent (16/81) of dogs developed neurologic signs. Neurologic signs included stupor, non-ambulatory tetraparesis, and generalized seizures. A significant association was found between the presence of neurologic signs and the baseline, peak, and fold-change of bilirubin concentration (P < .001). The odds of having neurologic signs were 12.2 (95% CI, 3.1-48.2) for dogs with baseline bilirubin concentrations ≥3.3 mg/dL (≥57.5 μmol/L), and 93.3 (95% CI, 11.0-795.5) for dogs with peak bilirubin concentrations ≥13.9 mg/dL (≥239.5 μmol/L).

Conclusions and clinical importance: Although the causation of the neurologic signs cannot be attributed solely to bilirubin based on our study, these findings emphasize the importance of monitoring serum bilirubin concentrations and the development of neurologic signs in dogs with IMHA. The results reflect findings in our study population and may not be directly applicable to all dogs with IMHA. © The Author(s) 2026.