Neutrophil to lymphocyte ratio (NLR)

 

The neutrophil to lymphocyte ratio (NLR) is used as a marker of subclinical inflammation. 

 

It is calculated by dividing the number of neutrophils by number of lymphocytes, usually from peripheral blood sample.

Under physiologic stress, the number of neutrophils increases, while the number of lymphocytes decreases.  

The NLR combines both of these changes, making it more sensitive than either alone:

Endogenous cortisol and catecholamines may be major drivers of the NLR.  

Increased levels of cortisol are known to increase the neutrophil count while simultaneously decreasing the lymphocyte count.​

Endogenous catecholamines may cause leukocytosis and lymphopenia.​

Cytokines and other hormones are also likely to be involved.

Thus, NLR is not solely an indication of infection or inflammation, as any cause of physiologic stress may increase the NLR, such as hypovolemic shock.

NLR increases rapidly, less than 6 hours, following acute physiologic stress.

The prompt response time may make NLR a better reflection of acute stress than white blood cell count or bandemia.

NLR may be calculated using either absolute cell counts or percentages.

A normal NLR is roughly 1-3.

An NLR of 6-9 suggests mild stress.

Critically ill patients will often have an NLR of ~9 or higher, occasionally reaching values close to 100.

Clinical situations influence NLR interpretation: inflammatory disorders may tend to elevate NLR more than non-inflammatory disorders. 

NLR has some similarities to bandemia – both may be used to discern physiologic stress in the absence of a grossly abnormal white blood cell count.

The primary advantage of NLR over bandemia might be that it is more reproducibly measurable.  

Exogenous steroid:  May directly increase the NLR.

Active hematologic disorder:  Leukemia, cytotoxic chemotherapy, or granulocyte colony stimulating factor (G-CSF) may affect cell counts.

Higher NLR is independent predictor of mortality in patients undergoing angiography or cardiac revascularization.

In septic shock low  levels of cortisol may correlate with somewhat increased mortality, reflecting  either exhaustion of the adrenal glands or underlying adrenal insufficiency.  

Lack of any cortisol response is pathological, leaving the patient vulnerable to stress.

Intermediate levels of cortisol seem to correlate with the best survival in septic shock.

Highest levels of cortisol correlate with the worst survival, as these patients are under extremely intense physiologic stress.

With septic shock a normal NLR is maladaptive, and carries an unfavorable prognosis.  

Persistent elevation of NLR over several days is a poor prognostic sign, raising a question of treatment failure:

trajectory of intracranial hemorrhage

Among patients with spontaneous intracranial hemorrhage, nonsurvivors experience an increase in NLR over 24-48 hours, whereas survivors had a stable NLR.  

NLR kinetics will vary depending on the natural history of any specific disease.

The NLR used in place of the white blood cell count, has proven to be far more accurate.   

Neutrophil-to-lymphocyte ratio (NLR) is easily calculated from the differential cell count. 

It is a reflection of physiologic stress, perhaps tied most directly to cortisol and catecholamine levels.

Increased NLR is associated with poor prognosis of various cancers.

 

NLR can be used as a prognostic marker for COVID-19, given the significant difference of NLR between those died and recovered from COVID-19. 

 

95% of healthy adults have a ratio between 0.78 and 3.53.

 

 

2.5% of healthy adults having less than 0.78, and 2.5% above 3.53.