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Case Presentation
A 5‐year‐old female spayed domestic long hair cat presented to the University of Minnesota Emergency Service with reported signs of lethargy, inappetence and increased hiding behaviour. At presentation, the patient was mildly dehydrated (approximately 5%) and was pyrexic (104.9°F), while the remainder of the physical exam was unremarkable. A complete blood cell count (CBC) (Table 1) revealed mild leucocytosis (19,730/µL; reference interval [RI]: 1830–16,270/µL) characterised by mild neutrophilia (990/µL; RI: 0–800/µL) and moderate thrombocytopenia (86,000/µL; RI: 110,000–413,000/µL). A serum biochemistry panel revealed marked elevations in alanine aminotransferase (ALT) (14,184 U/L; RI: 16–127 U/L) and aspartate aminotransferase (AST) (17,365 U/L; RI: 14–42 U/L). Additional abnormalities included a mild increase in total bilirubin (0.9 mg/dL; RI: 0.0–0.3 mg/dL), mild hyperglycaemia (201 mg/dL; RI: 74–143 mg/dL), mild hypokalaemia (3.8 mmol/L; RI: 3.9–5.3 mmol/L) and mild hypophosphatemia (2.8 mg/dL; RI: 3.3–7.8 mg/dL). Coagulation testing demonstrated markedly prolonged prothrombin time (> 150.0 s; 8.2–9.9 s) and partial thromboplastin time (>150.0 s; 10.0–21.9 s) with marked hypofibrinogenemia (40 mg/dL; 77–206 mg/dL). Urine was collected by cystocentesis for urinalysis as part of a complete diagnostic workup, which revealed hypersthenuric urine (specific gravity of 1.050), bilirubinuria (2+) and proteinuria (3+); all other urinalysis parameters were unremarkable. Additional infectious disease testing was performed. In‐house testing for feline leukaemia virus antigen and feline immunodeficiency virus antibody was negative. Send‐out CSU enzyme‐linked immunosorbent assay (ELISA) for toxoplasmosis IgG and IgM titres were negative.
TABLE 1. Serial laboratory data from a domestic long‐haired cat that presented with fever, severe liver disease and blue‒green neutrophilic inclusions on peripheral blood smear.
| Test | Day 1 | Day 3 | Day 5 | Reference intervals (RI) | Day 9 a | Reference intervals (RI) | Day 279 b | Reference intervals (RI) |
|---|---|---|---|---|---|---|---|---|
| CBC | ||||||||
| WBC | 19.73 H | 9.2 | 7.83 | 1.83–16.27 × 10 3 /µL | 6.4 | 3.9–19.0 × 10 3 /µL | 7.8 | 3.9–19 × 10 3 /µL |
| Neutrophils | 16.97 H | 5.24 | 5.25 | 1.20–13.20 × 10 3 /µL | 2.976 | 2.62–15.17 × 10 3 /µL | 3.409 | 2.62–15.1 × 10 3 /µL |
| Band neutrophils | 0.99 H | 0.00 | 0.16 | 0.00–0.16 × 10 3 /µL | ND | ND | ||
| Lymphocytes | 0.79 | 2.67 | 1.72 | 0.20–9.40 × 10 3 /µL | 3.053 | 0.85–5.85 × 10 3 /µL | 3.791 | 0.65–6.86 × 10 3 /µL |
| Monocytes | 0.99 H | 0.64 | 0.16 | 0.00–0.80 × 10 3 /µL | 0.083 | 0.04–0.53 × 10 3 /µL | 0.117 | 0.042–0.46 × 10 3 /µL |
| Eosinophils | 0.00 | 0.55 | 0.55 | 0.00–1.90 × 10 3 /µL | 0.224 | 0.09–2.18 × 10 3 /µL | 0.452 | 0.209–1.214 × 10 3 /µL |
| Basophils | 0.00 | 0.09 | 0.00 | 0.00–0.30 × 10 3 /µL | 0.064 | 1–0.1 × 10 3 /µL | 0.031 | High range: 0.1 |
| Nucleated RBC | 0/100 WBC | 0/100 WBC | 0/100 WBC | No RI | ND | ND | ||
| RBC | 8.08 | 6.85 | 7.25 | 6.44–10.36 × 10 6 /µL | 7.91 | 7.12–1.46 × 10 6 /µL | 8.39 | 6.5–11.53 × 10 6 /µL |
| HGB | 14.0 | 12.0 | 12.4 | 9.8–16.8 g/dL | 13.7 | 10.3–16.2 g/dL | 14.8 | 10.6–16.7 g/dL |
| HCT | 40.8 | 34.0 | 35.8 | 29.5%–47.0% | 42.8 | 28.2%–52.7% | 46.7 | 31%–51% |
| MCV | 50.5 H | 49.7 | 49.4 | 37.4–50.4 fL | 54 | 39–56 fL | 56 H | 38–53 fL |
| MCH | 17.4 | 17.5 | 17.2 | 14.0–18.0 pg | 17.3 H | 12.6–16.5 pg | 17.6 H | 12.3–17.3 pg |
| MCHC | 34.3 | 35.3 | 34.7 | 32.1–39.7 g/dL | 32.0 | 28.5–37.8 g/dL | 31.7 | 29.1–35.7 g/dL |
| RDW | 14.6 | 14.5 | 14.7 | No RI % | ND | No RI | 18.1 | 10%–26% |
| % Reticulocytes | 0.72 | 0.38 | 0.35 | 0.10%–0.80% | 0.6 | No RI | 0.1 | No RI |
| Reticulocytes | 0.058 | 0.026 | 0.025 | 0.004–0.066 × 10 6 /µL | 0.047 | 0.003–0.05 × 10 6 /µL | 0.008 | High range: 0.07 |
| Platelet count | 86 L | 92 L | 90 L | 110–413 × 10 3 /µL | 150 L | 155–641 × 10 3 /µL | 176 | 100–440 × 10 3 /µL |
| Chemistry | ||||||||
| BUN | 27 | 7 L | 13 | 12–39 mg/dL | 17 | 16–37 mg/dL | 21 | 16–37 mg/dL |
| Creatinine | 1.1 | 0.7 | 0.9 | 0.5–2.1 mg/dL | 0.9 | 0.9–2.3 mg/dL | 1.7 | 0.9–2.3 mg/dL |
| Calcium | 9.9 | 9.4 | 9.7 | 8.3–10.9 mg/dL | 9.9 | 8.2–11.2 mg/dL | 10.6 | 8.2–11.2 mg/dL |
| Phosphorus | 2.8 L | 3.3 | 4.6 | 3.3–7.8 mg/dL | 4.8 | 2.9–6.3 mg/dL | 4.0 | 2.9–6.3 mg/dL |
| Magnesium | 1.9 | 2.1 | 2.2 | 1.6–2.4 mg/dL | ND | ND | ||
| Total protein | 7.7 | 7.9 | 7.8 | 5.9–8.2 g/dL | 8.7 | 6.3–8.8 g/dL | 8.4 | 6.3–8.8 g/dL |
| Albumin | 3.4 | 3.4 | 3.1 | 2.4–4.1 g/dL | 3.1 | 2.6–3.9 g/dL | 3.8 | 2.6–3.9 g/dL |
| Globulin | 4.3 | 4.5 | 4.7 | 2.5–5.3 g/dL | 5.6 | 3.0–5.9 g/dL | 4.6 | 3–5.9 g/dL |
| Sodium | 148 | 149 | 156 | 147–158 mmol/L | 155 | 147–157 mmol/L | 153 | 147–157 mmol/L |
| Chloride | 116 | 116 | 123 | 113–123 mmol/L | 120 | 114–126 mmol/L | 119 | 114–126 mmol/L |
| Potassium | 3.8 L | 4.0 | 4.1 | 3.9–5.3 mmol/L | 4.4 | 3.7–5.7 mmol/L | 4.2 | 3.7–5.2 mmol/L |
| Bicarbonate | 18.4 | 15.6 | 17.3 | 12.0–20.0 mmol/L | 16 | 12–22 L mmol/L | 16 | 12–22 L mmol/L |
| Anion gap | 17 L | 21 | 20 | 19–30 | 23 | 12–25 | 22 | 12–25 |
| Total bilirubin | 0.9 H | 3.2 H | 3.1 H | 0.0–0.3 mg/dL | 1.2 H | 0.0–0.3 mg/dL | 0.1 | High range: 0.3 mg/dL |
| ALP | 27 | 30 | 135 H | 2–88 U/L | 147 H | 12–59 U/L | 23 | 12–59 U/L |
| GGT | 3 | < 3 | < 3 | 0–3 U/L | 1 | 0–6 U/L | 1 | High range: 6 U/L |
| ALT | 14,184 H | 8727 H | 3283 H | 16–127 U/L | 898 H | 27–158 U/L | 44 | 27–158 U/L |
| AST | 17,365 H | 2372 H | 447 H | 14–42 U/L | 182 H | 16–67 U/L | 12 | 16–67 U/L |
| CK | 124 | 157 | 70 | 54–744 U/L | 44 L | 64–440 U/L | 56 L | 64–440 U/L |
| Glucose | 201 H | 89 | 87 | 74–143 mg/dL | 77 | 72–175 mg/dL | 92 | 72–175 mg/dL |
| Cholesterol | 74 | 95 | 74 | 56–226 mg/dL | 130 | 91–305 mg/dL | 202 | 91–305 mg/dL |
| Amylase | 608 | 544 L | 614 | 555–1600 U/L | 835 | 623–2239 U/L | ND | |
| Coagulation | ||||||||
| PT | > 150.0 H | ND | ND | 8.2–9.9 s | ND | ND | ND | ND |
| APTT | > 150.0 H | ND | ND | 10.0–21.9 s | ND | ND | ND | ND |
| Fibrinogen | 40 L | ND | ND | 77–206 mg/dL | ND | ND | ND | ND |
Peripheral blood smear slides were stained with Wright‐Giemsa stain. Slide review demonstrated unremarkable changes to the erythrocytes. The thrombocytes were mildly decreased in density, with a moderate number of macroplatelets observed. Leucocytes were mildly increased in density and comprised predominantly segmented neutrophils and occasional bands. Neutrophils often display mild to moderate toxicity characterised by cytoplasmic vacuolisation, increased cytoplasmic basophilia and occasional Döhle bodies. Moderate numbers of neutrophils contain variable amounts of round to angular blue‒green inclusions in the cytoplasm (Figure 1). These blue‒green inclusions ranged in size from 0.61 to 2.18 µm in diameter, and the number of inclusions per cell ranged from 1 to 12. Approximately 5% of neutrophils (out of 100 evaluated) in the monolayer contained these blue‒green inclusions.
[图：Representative neutrophils with blue‒green inclusions (arrow) throughout the patient's peripheral blood smear. Wright‐Gi]
To further characterise the composition of the neutrophilic inclusions, special stains and autofluorescence analysis were performed. The Wright‐Giemsa‐stained slides were destained in methanol overnight. The inclusions were negative for iron on Prussian blue staining (Figure 2). The inclusions demonstrated autofluorescence when excited across a wavelength range of 400–650 nm (Figure 3). Unstained slides were submitted to the University of California, Davis, for Sudan black staining, and the inclusions stained positively (Figure 3).
[图：Representative neutrophils with multiple tan inclusions (arrow) are negative for Prussian blue staining, ×100 objective.]
[图：Intrinsic autofluorescence of the patient's neutrophils (Rows A–B) from a peripheral blood smear and positive control he]
Thoracic and abdominal point‐of‐care ultrasound was unremarkable except for a subjectively small and hypoechoic liver. Based on the clinical decision of the receiving clinicians, the cat was admitted to the critical care service and initially treated with PlasmaLyte + 15 mEq/L KCL intravenously (IV) at 30 mL/h, ondansetron 0.50 mg/kg IV q8, famotidine 1 mg/kg IV q12, vitamin K at 1 mg/kg subcutaneously (SQ) q12, cerenia 1 mg/kg IV q24, N‐acetylcysteine 140 mg/kg IV once and then 70 mg/kg IV q6. A one‐time transfusion of 20 mL of fresh frozen plasma, transfused over 4 h, was also given due to the markedly prolonged coagulation times and desire to proactively reduce the risk of bleeding in case any abdominal fine‐needle aspirates (FNA) would be pursued. The cat was hospitalised for two nights with the following additional treatments: clindamycin 14 mg/kg q12 IV, vitamin E at 400 IU given by mouth (PO) q24, vitamin C at 28.6 mg/kg PO q8 and B complex 0.3 mL diluted 1:10 in LRS IV q24. Repeat blood work (Table 1) on Day 3 of hospitalisation revealed normalised leucocyte values, static platelet count (92,000/µL), and improvement in liver enzymes (ALT—8727 H U/L, AST—2372 U/L) with a mild decrease in BUN value (7 mg/dL). Clinically, the cat was significantly improved in light of the blood work values, discharged on Day 3 and sent home with clindamycin 25 mg/mL oral solution for 10 days, transdermal mirtazapine for 7 days, S‐adenosyl chew 26 mg/kg PO q24 for 14 days and ondansetron 0.5 mg/kg PO q8 for 7 days. A complete CBC and serum biochemistry panel were rechecked on Days 5, 9 and 279 after discharge, and the results are included in Table 1. Values displayed a continual trend of improving platelet counts and liver enzymes. The owner reported that on Day 9, there was a noticeable improvement in the cat's overall appearance and health, which remained consistent with the last follow‐up obtained on Day 279.
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Discussion
Green‒blue neutrophilic inclusions are infrequently reported in human medicine but are believed to be an early prognostic indicator of sudden mortality (Hodgson et al. 2015). These inclusions have been associated with acute hepatic failure, lactic acidosis with multisystem organ failure after trauma, and Escherichia coli‐associated septic shock in people (Hodgson et al. 2015; Soos et al. 2019). Green‒blue neutrophil inclusions are rarely reported in veterinary medicine. A single publication reporting these inclusions in canine leucocytes identified them in dogs with severe hepatocellular damage, the majority of which were euthanised shortly after presentation (Sebastian et al. 2024). In dogs, these inclusions are described as lipofuscin‐like substances that are positive for autofluorescence and Prussian blue negative (Sebastian et al. 2024).
Although the exact mechanism of the formation of these lipofuscin‐like inclusions remains unknown, one theory proposes that acute hepatic injury leads to the release of lipofuscin from necrotic hepatocytes, which is subsequently phagocytosed by macrophages and neutrophils, resulting in the formation of blue‒green cytoplasmic inclusion bodies (Soos et al. 2019). In dogs and cats, lipofuscin pigment is present in both normal and injured hepatocytes (Masserdotti 2025; Courtman and Quilez 2025) and often results from oxidative degradation of membranous organelles within hepatocyte lysosomes during degenerative processes (Goldfischer and Bernstein 1969). Lipofuscin is commonly thought of as the ‘wear and tear pigment and a normal aging product of cellular turnover’ (Raskin et al. 2022). In cats, lipofuscin is seen in hepatocytes after a few years of age, and the amount seen can depend on the nature of the hepatocellular injury (Masserdotti 2025).
Lipofuscin is an autofluorescent, lipid‐rich pigment composed of oxidised proteins and lipids (Masserdotti 2025; Courtman and Quilez 2025). Positive Sudan black staining and autofluorescence, with emission extending from 570 to 605 nm following excitation at 366 nm, are well‐established characteristics of lipofuscin in human tissues (Salmonowicz and Passos 2017; Skoczyńska et al. 2017; Jung et al. 2007; Terman and Brunk 2004). A previous report in dogs similarly documented lipofuscin within peripheral blood neutrophils that was negative for Prussian blue staining, and the pigment was autofluorescent (Sebastian et al. 2024). In the presented case, the neutrophil inclusions were negative for Prussian blue staining, positive for Sudan black staining, and demonstrated autofluorescence, which collectively indicates lipofuscin as the most likely composition of the blue‒green neutrophilic inclusions. Additional diagnostics not performed in this case that could be considered in future investigations include electron microscopy, which has been used in human studies to identify lipofuscin within peripheral blood neutrophils (Hodgson et al. 2015).
This cat presented with a marked ALT elevation of 14,184 U/L, which decreased dramatically to 898 U/L by Day 9 and normalised by Day 279. ALT elevations of this severity have been reported to gradually decline toward normal over a 2‐ to 3‐week period following resolution of the inciting insult (Center 2007). The initial magnitude of the ALT and AST elevations indicates marked acute hepatocellular injury in this patient, and as cholestatic enzymes (ALP and GGT) were within the reference intervals, these findings are most consistent with a primary liver insult. Liver enzyme elevations of this magnitude in cats are associated with hepatocellular necrosis, hepatitis and hepatic toxicity (i.e., acetaminophen) (Center 2007). One potential cause of the elevated liver enzyme activities in this patient was hepatitis. Feline hepatitis can develop secondary to a variety of aetiologies, including infectious agents (viral, bacterial, protozoal and fungal), idiopathic processes and hepatotoxin exposure (Rondeau 2015). Although no history of toxin exposure was identified, the other potential causes of hepatitis could not be definitively excluded. As liver biopsy and histopathology were not performed, the exact cause for the elevations was not determined.
In conclusion, this report describes blue‒green neutrophilic inclusions in a cat with fever and severe acute hepatopathy that underwent complete disease resolution and demonstrated long‐term survival. To our knowledge, this represents the first reported case of blue‒green neutrophilic inclusions in a cat with severe liver disease. Moreover, this case further illustrates the prognostic heterogeneity of this finding, although a larger number of feline cases are needed to fully characterise the relationship between these inclusions and clinical outcomes.
Author Contributions
Zynia R. Alvarez: conceptualisation, investigation, writing – original draft, writing – review and editing, methodology, resources, project administration, visualisation, data curation, formal analysis, software. Kimberly M. Demos‐Davies: project administration, resources, supervision, methodology, writing – review and editing, visualisation, conceptualisation, investigation, writing – original draft, data curation, formal analysis, software. Ian M. Hubbard: data curation, resources, methodology. Davis M. Seelig: conceptualisation, supervision, writing – review and editing, writing – original draft. Angela D. Gwynn: conceptualisation, investigation, writing – original draft, writing – review and editing, supervision, data curation, resources, project administration, formal analysis, funding acquisition.
Funding
The authors have nothing to report.
Consent
The authors have nothing to report.
Conflicts of Interest
The authors declare no conflicts of interest.