Evaluation of anemia

Anemia is a hemoglobin (Hb) level two standard deviations below the mean for the age and sex of the patient. Reference ranges vary between laboratories. The World Health Organization (WHO) recommends the following hemoglobin cutoffs to define anemia in the individual:[1]World Health Organization. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240088542

• Hb <10.5 g/dL in children ages 6 to 23 months

• Hb <11 g/dL in children ages 24 to 59 months

• Hb <11.5 g/dL children ages 5 to 11 years

• Hb <12 g/dL in children ages 12 to 14 years

• Hb <12 g/dL in nonpregnant adult females (ages 15 years and over)

• Hb <13 g/dL in adult males (ages 15 years and over)

• Hb <11 g/dL during the first trimester pregnancy

• Hb <10.5 g/dL during the second trimester pregnancy

• Hb <11 g/dL during the third trimester pregnancy

​Adjustments to hemoglobin cut-off values may be required, according to external factors, such as cigarette smoking and the population’s elevation above sea level.[1]World Health Organization. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. Mar 2024 [internet publication]. https://www.who.int/publications/i/item/9789240088542 ​​

Anemia is commonly seen in general medical practice.[2]Gandhi SJ, Hagans I, Nathan K, et al. Prevalence, comorbidity and investigation of anemia in the primary care office. J Clin Med Res. 2017 Dec;9(12):970-80. https://www.doi.org/10.14740/jocmr3221w http://www.ncbi.nlm.nih.gov/pubmed/29163729?tool=bestpractice.com [3]Milovanovic T, Dragasevic S, Nikolic AN, et al. Anemia as a problem: GP approach. Dig Dis. 2022;40(3):370-5. http://www.ncbi.nlm.nih.gov/pubmed/34098557?tool=bestpractice.com ​ Risk factors include extremes of age, female sex, lactation, and pregnancy. The most common cause of anemia globally is dietary iron deficiency.[4]Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015 May 7;372(19):1832-43. http://www.ncbi.nlm.nih.gov/pubmed/25946282?tool=bestpractice.com [5]GBD 2021 Anaemia Collaborators. Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021. Lancet Haematol. 2023 Sep;10(9):e713-34. https://pmc.ncbi.nlm.nih.gov/articles/PMC10465717 http://www.ncbi.nlm.nih.gov/pubmed/37536353?tool=bestpractice.com ​​​​​

Anemia can cause significant morbidity if left untreated, and is often the presenting sign of a more serious underlying condition.[6]Thein M, Ershler WB, Artz AS, et al. Diminished quality of life and physical function in community-dwelling elderly with anemia. Medicine (Baltimore). 2009 Mar;88(2):107-14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893336 http://www.ncbi.nlm.nih.gov/pubmed/19282701?tool=bestpractice.com The rate at which anemia develops is often as important as the severity, as a rapid decline can overwhelm the compensatory mechanisms of the body.

For all population groups combined, the Global Burden of Disease Study (2021) estimated that approximately 24% of the world’s population had some form of anemia, affecting 1.9 billion people.[5]GBD 2021 Anaemia Collaborators. Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021. Lancet Haematol. 2023 Sep;10(9):e713-34. https://pmc.ncbi.nlm.nih.gov/articles/PMC10465717 http://www.ncbi.nlm.nih.gov/pubmed/37536353?tool=bestpractice.com ​​ Sub-Saharan Africa and South Asia are particularly affected.[5]GBD 2021 Anaemia Collaborators. Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021. Lancet Haematol. 2023 Sep;10(9):e713-34. https://pmc.ncbi.nlm.nih.gov/articles/PMC10465717 http://www.ncbi.nlm.nih.gov/pubmed/37536353?tool=bestpractice.com

The WHO estimated that 30.7% of women of reproductive age were anemic in 2023, with the highest prevalence in South-East Asia and Africa.[7]World Health Organization. ​WHO global anaemia estimates: key findings, 2025. Aug 2025 [internet publication]. https://www.who.int/publications/i/item/9789240113930

Globally, in 2019, 40% of children ages 6-59 months were anemic.[8]Stevens GA, Paciorek CJ, Flores-Urrutia MC, et al. National, regional, and global estimates of anaemia by severity in women and children for 2000-19: a pooled analysis of population-representative data. Lancet Glob Health. 2022 May;10(5):e627-39. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(22)00084-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35427520?tool=bestpractice.com

Pathophysiology

Erythropoiesis takes place within the bone marrow and is controlled by the stromal network, cytokines, and the hormone erythropoietin. Through a series of differentiation steps, hematopoietic stem cells become reticulocytes (red blood cells [RBCs] with an intact ribosomal network).

Reticulocytes remain in the bone marrow for 3 days before being released into the circulation. After approximately one day in the circulation, reticulocytes lose their ribosomal network and become mature RBCs, which circulate for 110-120 days before being removed from the circulation by macrophages.[9]Stevens-Hernandez CJ, Bruce LJ. Reticulocyte maturation. Membranes (Basel). 2022 Mar 10;12(3). https://www.doi.org/10.3390/membranes12030311 http://www.ncbi.nlm.nih.gov/pubmed/35323786?tool=bestpractice.com

Anemia develops when the rate of RBC production decreases and/or the rate of RBC loss increases.

Morphological classification of anemia

The most clinically useful classification system is based on the mean corpuscular volume (MCV).[3]Milovanovic T, Dragasevic S, Nikolic AN, et al. Anemia as a problem: GP approach. Dig Dis. 2022;40(3):370-5. http://www.ncbi.nlm.nih.gov/pubmed/34098557?tool=bestpractice.com ​​

• Microcytic (MCV <80 femtoliters [fL]).[Figure caption and citation for the preceding image starts]: Microcytic anemiaFrom the collection of Dr Robert Zaiden; used with permission [Citation ends].

• Normocytic (MCV 80-100 femtoliters [fL]); can be hyperproliferative or hypoproliferative.

  • Hyperproliferative (reticulocyte count >2%): the proportion of circulating reticulocytes increases as part of a compensatory response to increased destruction or loss of RBCs. The cause is usually acute blood loss or hemolysis.

  • Hypoproliferative (reticulocyte count <2%): primarily disorders of decreased RBC production, and the proportion of circulating reticulocytes remains unchanged.

• Macrocytic (MCV >100 femtoliters [fL]); can be megaloblastic or nonmegaloblastic.

  • Megaloblastic: a deficiency of DNA production or maturation resulting in the appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation.

  • Nonmegaloblastic: encompasses all other causes of macrocytic anemia in which DNA synthesis is normal. Megaloblasts and hypersegmented neutrophils are absent.[Figure caption and citation for the preceding image starts]: Megaloblastic macrocytic anemiaFrom the collection of Dr Robert Zaiden; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Classification of anemia: MCV, mean corpuscular volume; fL, femtolitersCreated by the BMJ Knowledge Centre [Citation ends].