Low lymphocyte count points to increased mortality risk

Editor’s note: This article, originally posted on Jan. 15, 2020, has been republished to include website enhancements.

Low levels of lymphocytes in the blood could indicate an increased risk for death, according to a study published in CMAJ.

This condition, known as lymphopenia, is often detected during routine blood tests, according to Stig E. Bojesen, MD, clinical professor in the department of clinical medicine at the University of Copenhagen, Denmark, and colleagues. Patients with lymphopenia are usually not referred for further examination because the clinical implications of the condition were previously unknown.

“We do not know whether lymphopenia is a cause of increased mortality or only a marker of generally reduced health, but in both cases, the lymphopenic individual might benefit from increased attention from her or his physician,” Bojesen told Healio Primary Care.

Bojesen and colleagues conducted a prospective cohort study of adults aged 20 to 100 years who were enrolled in the Copenhagen General Population Study between November 2003 and April 2015. They collected data on all participant deaths before Apr. 19, 2018, with information on cause of death available through Dec. 31, 2015.

Participants had their blood drawn and white blood cell counts measured as part of a physical examination.

Researchers defined lymphopenia as a lymphocyte count below the 2.5th percentile (less than 1.1 × 10⁹/L). A high lymphocyte count above the 97.5th percentile (more than 3.7 × 10⁹/L) was categorized as lymphocytosis. Lymphocyte counts between this range (1.1-3.7 × 10⁹/L) fell into the reference category.

To account for declining lymphocyte count with age, researchers calculated the age-adjusted 2.5th percentile for every 10-year age group.

A total of 108,136 individuals with a median age of 68 years were evaluated in the study. Of those, 10,372 died during a median follow-up period of 9 years.

After adjusting for multiple factors, those with lymphopenia had higher risk for all-cause mortality compared with those in the reference group (HR = 1.63; 95% CI, 1.51-1.76).

Those with lymphopenia also had higher risks for mortality from nonhematologic cancer (HR = 1.67; 95% CI, 1.42-1.97), hematologic cancer (HR = 2.79; 95% CI, 1.82-4.28), cardiovascular disease (HR = 1.88; 95% CI, 1.61-2.2), respiratory diseases (HR = 1.88; 95% CI, 1.55-2.29) and infectious diseases (HR = 1.86; 95% CI, 1.53-2.25) compared with those in the reference group. The risk for death was also increased in those with lymphopenia for other causes (HR = 1.5; 95% CI, 1.19-1.88).

Participants with lymphocytosis also experienced an increased risk for mortality compared with the reference group (HR = 1.17; 95% CI, 1.04-1.31).

The risk for all-cause mortality with lymphopenia was more pronounced in participants aged 70 years or younger compared with those aged more than 70 years.

The absolute 2-year risk for all-cause mortality was highest in men and women who smoked, were aged at least 80 years, and had a lymphocyte count below 0.5 × 10⁹/L.

The study authors suggested that lymphopenia may be an indicator for frailty or lead to reduced immune surveillance.

Bojesen told Healio Primary Care that if physicians identify a patient with lymphopenia, they should “take this marker of increased mortality seriously, and, dependent on the individual’s other risk factors, increase clinical surveillance and help to improve the overall health.”