Smoking triggers red blood cell death, raising anemia and circulation concerns

A study published in the journal Scientific Reports finds that cigarette smoking can trigger suicidal erythrocyte death, a condition that may increase the risk of anemia and microcirculation impairment.

Study: Smoking is associated with increased eryptosis, suicidal erythrocyte death, in a large population-based cohort. Image Credit: sruilk / Shutterstock


Smoking is a leading cause of premature morbidity and mortality worldwide. Tobacco smoke contains many harmful substances, including carbon monoxide, formaldehyde, acetaldehyde, benzopyrenes, and nicotine, which can enter the bloodstream through inhalation and cause cardiovascular complications. Moreover, carbon monoxide can bind to hemoglobin to form carboxyhemoglobin, which reduces the oxygen-carrying capacity of hemoglobin and subsequently induces hypoxic effects.

Previous studies investigating the impact of smoking on the red blood cell system provide mixed results. While some studies show higher red blood cell indices in smokers compared to non-smokers, some indicate that smoking can induce eryptosis. Eryptosis is a process of erythrocyte (red blood cell) death, characterized by phosphatidylserine externalization and cell shrinkage.

In this large population-based cohort study, scientists have investigated the impact of smoking on eryptosis and vital hematological parameters, including red blood cell count, hematocrit, hemoglobin, mean corpuscular cell volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).  

Study design

The current study included 2,023 participants from the German National Cohort Study (NAKO), which includes more than 205,000 adult participants across 18 study centers in different German states.

Blood samples collected from the participants were analyzed for eryptosis and hematological parameters. Eryptosis was determined using flow cytometry, and red blood cell indices were determined using a hematological analyzer.

Important observations

Among 2,023 participants included in the study, 1,000 were non-smokers, 418 were current smokers, and 605 were ex-smokers.

The comparative analysis between smoking habits and eryptosis revealed that smokers have a moderately higher rate of eryptosis than non-smokers and ex-smokers. Specifically, smokers showed 14% and 19% higher percentages of eryptotic cells compared to non-smokers and ex-smokers, respectively. However, no significant difference in eryptosis was observed between non-smokers and ex-smokers.

Furthermore, the study found a positive association between the number of cigarettes smoked per day and the rate of eryptosis. This association remained the same for both male and female smokers. However, no association between the smoking burden per year and the rate of eryptosis was observed in the entire study population.   

A subgroup analysis including ex-smokers revealed a negative association between the duration of smoking cessation and the rate of eryptosis. The age of smoking cessation and the time since smoking cessation were identified as significant predictors of eryptosis in ex-smokers.

Regarding hematological parameters, no association of eryptosis was observed with erythrocyte count, hemoglobin, hematocrit, and MCV. However, there was a moderately positive association between eryptosis and MCH and MCHC. 

No significant differences in erythrocyte count and hematocrit were observed between smokers, non-smokers, and ex-smokers. However, smokers showed higher levels of hemoglobin, MCV, MCH, and MCHC than the rest.

The daily number of cigarettes smoked, smoking duration, and annual smoking burden showed a moderately positive association with hematocrit, hemoglobin, MCV, and MCH and a negative association with MCHC in current smokers.  

Study significance

The study finds that current smokers have a moderately higher rate of suicidal erythrocyte death than non-smokers and ex-smokers. However, despite higher erythrocyte death, smokers have comparatively higher erythrocyte indices. This indicates that higher eryptosis in smokers has no apparent negative impact on the overall red blood cell system.

According to the available literature, smoking-induced oxidative stress and inflammation may play a role in triggering eryptosis. Carbon monoxide inhaled during smoking has also been found to stimulate eryptosis directly. Moreover, the p38MAPK/Fas signaling pathway has been found to increase the eryptosis rate in smokers.

Despite higher erythrocyte death, the study found fewer erythrocyte counts among smokers. This could be due to enhanced erythropoiesis (the process of producing new erythrocytes) in smokers to compensate for the eryptosis-mediated loss of erythrocytes.

As mentioned by the scientists, including a large number of participants is the study's major strength. However, self-reported smoking status can be subjected to reporting bias. The scientists are looking forward to studying whether increased eryptosis is associated with a higher risk of cardiovascular disease in smokers. 

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.


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  1. Angus McPhail Angus McPhail Australia says:

    We now have Hemoglobinopathy traits, (Inherited), Hemolytic Anemia, Iron; VitB12: and Folate deficiencies, Heavy Menstruation, and now smoking, ALL confound the Diabetes Diagnostic Test HbA1c giving false Lows and highs, These Variant hemoglobin lifespans  mainly found in our Ethnic populations and Woman in general. See" NIDDK ethnicities and A1c"for explanation on carrier traits in susceptible populations, Note the errors that GPs are making in the URL above
    Solution a Fasting A1c with a Fasting glucose test should be implemented. Any discordance between these, Highlights Red blood cell survival problems th PATH LABS and they should be responsible for Alerting GPs that further tests are required such as Fructosamine

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