What is the clinical significance of an elevated neutrophil (white blood cell) to lymphocyte (white blood cell) ratio (NLR) in dogs and cats?

Neutrophil-to-Lymphocyte Ratio in Dogs and Cats

Clinical Significance and Diagnostic Utility

The neutrophil-to-lymphocyte ratio (NLR) serves as a clinically useful biomarker of systemic inflammation in dogs and cats, with elevated values (particularly NLR ≥5.5) indicating more severe inflammatory disease states and helping distinguish between different disease subtypes, particularly in chronic enteropathy where it can differentiate food-responsive from immunosuppressant-responsive disease. 1

Disease-Specific Applications

Chronic Enteropathy in Dogs

• Dogs with steroid-responsive or immunosuppressant-responsive enteropathy (IRE) have significantly higher NLR (median 7.3) compared to dogs with food-responsive enteropathy (FRE, median 3.0), with NLR ≥5.5 providing optimal discrimination between these groups. 1
• NLR correlates with disease severity, being significantly higher in dogs with severe clinical signs compared to mild disease. 1
• Higher NLR values are associated with hypoalbuminemia and correlate with fecal alpha1-proteinase inhibitor concentrations (ρ = 0.47), suggesting intestinal protein loss. 1
• NLR does not correlate with histologic severity scores or serum inflammatory markers, indicating it reflects systemic rather than local intestinal inflammation. 1

Acute Pancreatitis

• Both dogs and cats with acute pancreatitis demonstrate significantly elevated NLR and platelet-to-lymphocyte ratio (PLR) compared to healthy controls. 2
• While NLR and PLR do not predict disease severity as measured by modified BISAP scores, PLR is significantly increased in both dogs and cats with prolonged recovery, and NLR is significantly elevated in cats (but not dogs) with prolonged recovery. 2
• These ratios provide prognostic information about disease course rather than initial severity. 2

Hypertrophic Cardiomyopathy in Cats

• Cats with cardiogenic arterial thromboembolism (CATE) have the highest NLR (median 5.8, range 3.1-12.7) compared to cats with HCM alone or healthy controls. 3
• Cats with HCM have elevated NLR (median 3.3, range 1.8-5.1) compared to healthy controls, suggesting systemic inflammation plays a role in feline HCM. 3
• The platelet-to-neutrophil ratio (PNR) below 40 is a superior prognostic marker in cats with early subclinical HCM, with affected cats having significantly shorter median survival (1093-1185 days) and a 9.8-fold increased risk of cardiac-related mortality. 3
• PNR outperforms both NLR and echocardiographic findings for prognostication in early-stage HCM. 3

Immune-Mediated Hemolytic Anemia in Dogs

• In dogs with primary IMHA, leukocyte ratios (NLR, neutrophil-to-monocyte ratio, monocyte-to-lymphocyte ratio) do not reliably predict survival to discharge when all cases are analyzed together. 4
• However, in untreated dogs (those not receiving immunosuppressants or transfusions before presentation), lower monocyte-to-lymphocyte ratio and higher neutrophil-to-monocyte ratio significantly predict poorer prognosis. 4
• This suggests pre-treatment ratios may have prognostic value, but therapeutic interventions confound interpretation. 4

Physiological Basis

• NLR increases during stress and inflammation because stress hormones cause neutrophils to increase while simultaneously causing lymphocytes to decrease, with lymphocytes showing a biphasic pattern (initial increase, then strong decrease for up to 36 hours) while neutrophils continue rising for 4-6 hours after stress ends. 5
• Fitness level, nutritional status, sex, and temperature influence both baseline white blood cell levels and acute stress responses. 5

Practical Clinical Algorithm

When to Calculate NLR in Dogs and Cats:

1. Chronic diarrhea/enteropathy: Calculate NLR from routine CBC to help predict treatment response

   • NLR <5.5 suggests likely food-responsive disease 1
   • NLR ≥5.5 suggests need for immunosuppressive therapy 1

2. Acute pancreatitis: Calculate both NLR and PLR at presentation and during hospitalization

   • Elevated values confirm diagnosis 2
   • Monitor PLR (and NLR in cats) to predict recovery time 2

3. Feline cardiomyopathy: Calculate PNR (not NLR) at HCM diagnosis

   • PNR <40 indicates high-risk patients requiring closer monitoring 3
   • PNR >40 suggests better long-term prognosis 3

4. IMHA evaluation: Calculate ratios before initiating treatment

   • Post-treatment values are unreliable for prognosis 4

Important Caveats

• NLR is easily calculated from routine complete blood counts, making it a cost-effective and accessible biomarker requiring no additional testing. 3, 1
• Pre-analytical factors including recent steroid administration, stress, and concurrent infections will artificially elevate NLR and confound interpretation. 4, 1
• NLR reflects systemic inflammation but does not localize disease or identify specific etiologies—it must be interpreted within the complete clinical context. 1
• In feline cardiac disease, PNR appears superior to NLR for prognostication, representing a paradigm shift from traditional inflammatory markers. 3