Resolution of Canine Acute Bilirubin Encephalopathy and Immune-Mediated Hemolytic Anemia Following Four Plasmapheresis Treatments.

An 8 mo old spayed female mixed-breed dog was presented for pale mucous membranes. The dog was diagnosed with intravascular immune-mediated hemolytic anemia (IMHA) and was started on medical management including corticosteroids, thromboprophylaxis, a packed red blood cell transfusion, and IV immunoglobulin. The dog developed severe hyperbilirubinemia (total bilirubin 48.1 mg/dL) and was referred for centrifugal plasmapheresis. Before treatment, the dog was stuporous to comatose, had intermittent opisthotonos, forelimb extension, and an absent menace consistent with acute bilirubin encephalopathy (ABE). The dog underwent a previously reported protocol of three therapeutic plasma exchange (TPE) treatments 24 hr apart. Moderate improvement was noted in her neurological status, although autoagglutination and hemolysis persisted, and the protocol was deemed inadequate. A fourth TPE treatment was performed on day 6. The following morning, the dog was autoagglutination negative. Her neurological status gradually improved, and she was discharged from the hospital on day 12. The dog remains neurologically normal and continues to do well at home on monotherapy with mycophenolate. Continued plasmapheresis treatments should be offered as a treatment option for severe cases of IMHA in the face of persistent disease, because TPE is able to provide ongoing support and stabilization, particularly in the face of ABE.

Identifying potential biomarkers and therapeutic targets for dogs with sepsis using metabolomics and lipidomics analyses.

Sepsis is a diagnostic and therapeutic challenge and is associated with morbidity and a high risk of death. Metabolomic and lipidomic profiling in sepsis can identify alterations in metabolism and might provide useful insights into the dysregulated host response to infection, but investigations in dogs are limited. We aimed to use untargeted metabolomics and lipidomics to characterize metabolic pathways in dogs with sepsis to identify therapeutic targets and potential diagnostic and prognostic biomarkers. In this prospective observational cohort study, we examined the plasma metabolomes and lipidomes of 20 healthy control dogs and compared them with those of 21 client-owned dogs with sepsis. Patient data including signalment, physical exam findings, clinicopathologic data and clinical outcome were recorded. Metabolites were identified using an untargeted mass spectrometry approach and pathway analysis identified multiple enriched metabolic pathways including pyruvaldehyde degradation; ketone body metabolism; the glucose-alanine cycle; vitamin-K metabolism; arginine and betaine metabolism; the biosynthesis of various amino acid classes including the aromatic amino acids; branched chain amino acids; and metabolism of glutamine/glutamate and the glycerophospholipid phosphatidylethanolamine. Metabolites were identified with high discriminant abilities between groups which could serve as potential biomarkers of sepsis including 13,14-Dihydro-15-keto Prostaglandin A2; 12(13)-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid); and 9-HpODE (9-Hydroxyoctadecadienoic acid). Metabolites with higher abundance in samples from nonsurvivors than survivors included 3-(2-hydroxyethyl) indole, indoxyl sulfate and xanthurenic acid. Untargeted lipidomic profiling revealed multiple sphingomyelin species (SM(d34:0)+H; SM(d36:0)+H; SM(d34:0)+HCOO; and SM(d34:1D3)+HCOO); lysophosphatidylcholine molecules (LPC(18:2)+H) and lipophosphoserine molecules (LPS(20:4)+H) that were discriminating for dogs with sepsis. These biomarkers could aid in the diagnosis of dogs with sepsis, provide prognostic information, or act as potential therapeutic targets.