Article Author:
Jake Turner
Article Editor:
Madhu Badireddy
1/16/2019 10:19:28 PM
PubMed Link:


Anemia is defined as reduction in hemoglobin (Hb) or hematocrit (HCT) or RBC count. Anemia is a not a diagnosis but a presentation of underlying conition. It can be subdivided into macrocytic versus microcytic or normocytic.

Normal Hb-specific laboratory cut-offs will differ slightly, but in general, the normal ranges are as follows:

  • 13.5 to 18.0 g/dL in men
  • 12.0 to 15.0 g/dL in women
  • 11.0 to 16.0 g/dL in children
  • Varied in pregnancy depending on the trimester, but generally greater than 10.0 g/dL.

Although there are conditions where much lower hemoglobin levels are acceptable, patients require a transfusion if they are symptomatic with a hemoglobin of less than 7.0 g/dL, or less than 8.0 g/dL if they have cardiac disease due to the increased risk of impaired perfusion of the myocardium in anemia.


The etiology of anemia can be broadly split into acute anemia or chronic anemia.

Acute causes include acute blood loss, radiotherapy, infections, and other causes of hemolysis, for example, hemolytic crises in sickle cell patients.

Chronic causes can be chronic blood loss as with menorrhagia or slow gastrointestinal (GI) bleeding, dietary deficiency including low iron, folate, or B12, or anemia of chronic disease.

Anemia can also caused by problems with the kidneys which leads to reduced erythropoietin production.

Certain medications, alcohol, and cancer invading the bone marrow can also cause bone marrow suppression, leading to reduced production of red blood cells.

Certain nonhematological diseases can cause anemia, for example, inflammatory bowel disease affecting the terminal ileum (classically Crohn's disease) [1], leading to impaired B12 absorption.

Etiology of anemia based on mean corpuscular volume (MCV) of RBC

1. Microcytic anemia (MCV <80 fL) 

  • Iron defeciency anemia [0]
  • Anemia of chronic disease
  • Siderobalstic anemia [0]
  • Thalassemia

2. Normocytic anemia (MCV 80-100 fL)

  • Anemia of chronic disease
  • Bone marrow suppression

3. Macrtocytic anemia (MCV >100 fL)

  • Alcohol and liver disease
  • Hypithyroidism
  • Folic acid and Vitmain B12 deficiency[4]
  • Drug induced


Classically, mild iron-deficiency anemia is seen in women of childbearing age, usually due to a poor dietary intake of iron and monthly loss during their periods. Anemia is also common in elderly patients, often due to poor nutrition. Other at-risk groups include people with alcoholism, the homeless population, and those experiencing neglect or abuse. New-onset anemia, especially in those over 55 years of age, needs investigating and should be considered to be due to cancer until proven otherwise.

Anemia is an extremely common disease affecting up to one-third of the global population. In many cases, it is mild and asymptomatic and requires no management further than oral iron replacement or dietary changes.


The pathophysiology of anemia varies greatly depending on the primary cause. For instance, in acute hemorrhagic anemia, it is the restoration of blood volume with intracellular and extracellular fluid that dilutes the remaining red blood cells (RBCs) to create anemia. In iron-deficiency anemia, because there is not enough iron to produce fully functional hemoglobin, fewer red cells mature and those that do often contain less hemoglobin, hence the hypochromic nature of iron-deficiency anemia. In anemia of chronic disease, prolonged inflammation causes changes in intracellular iron metabolism that leads to reduced levels of iron in the bloodstream. This is likely because iron is extremely good for bacterial growth and infections, so reducing the iron content of the blood can help to slow the spread of infection. Unfortunately, in chronic disease states, this process backfires and leads to prolonged iron deficiency-type anemias.

RBC are produced in the bone marrow and released into circulation. Approximately 1% of RBC are removed from circulation per day. Imbalance in production to removal or destruction of RBC leads to anemia [5]

1. Increased RBC destruction

  • Hemolytic anemia, acquired versus inherited

2. Decreased RBC production

  • Ineffective erythropoiesis
  • Malnutrition and malabsorption
  • Bone marrow disorders
  • Hormonal problems

3. Blood loss

  • Surgery
  • Trauma
  • Gastrointestinal bleeding[6]
  • Menstrual bleeding

History and Physical

Classically, patients with anemia will present with vague symptoms of weakness, tiredness, and lethargy. If severe, patients may complain of shortness of breath, especially on exertion, near syncope and reduced exercise tolerance. They may also complain of looking pale and feeling unwell. If patients with anemia complain of chest pain, then they would require urgent evaluation for ischaemic heart disease, as the decreased oxygen carrying capacity of the blood leads to an increase in cardiac work, along with decreased perfusion of the myocardium.

Physical examination can reveal pallor, jaundice, tachycardia, tachyapnea and even orthostatic hypotension in patients with severe anemia.


The main investigations required are laboratory blood work-up.

This includes

1. Complete blood count (CBC) including differentials to look for microcytic or macrocytic anemia and hypochromic or normochromic anemia.

2. Comprehensive metabolic panel.

3. Iron studies which include serum iron, iron banding capacity, serum ferritin and transferrin levels.

4. Vitamin B12 and folic acid levels and TSH.

5. Stool for occult blood.

A peripheral blood smear can also be useful in identifying other causes of anemia, such as sickle cell disease, Heinz body anemia or other, other hemoglobinopathies [0]

Anemia in neonates requires a slightly different evaluation and should include assessment of conjugated bilirubin levels because neonates are at risk of kernicterus and other issues secondary to the breakdown products of heme, and anemia may be an initial finding of hemolysis.

Other work up that might be needed include hemoglobin electrophoresis, bone marrow examination, esophagogastroduodenoscopy, colonoscopy and imaging studies if malignancy suspected.

Treatment / Management

Management depends on the cause of the anemia. If due to dietary deficiency, oral supplementation is preferred (iron, B12, and folate), although intravenous (IV) iron can also be given if a rapid resolution is needed. If a patient is unstable and severely anemic, consider a blood transfusion as well as supplementation. If due to blood loss, minimize the blood loss; if menorrhagia, give mefenamic acid and tranexamic acid to reduce blood loss. If due to other factors, treat those as appropriate, and consider supplementation with iron, B12, and folate to help repopulate the red blood cells.

Differential Diagnosis

Hemolysis during phlebotomy may lead to a falsely low red cell count, as may significant hemodilution, for example, in septic patients requiring large volume fluid resuscitation. In acute anemia from trauma, anemia may not immediately be present on blood tests, as the fluid shifts have not had time to occur to normalize the circulating volume, thus diluting the number of red blood cells remaining.


The prognosis for anemia is generally very good. Therapy with substrate replacement (iron, B12, folate) should begin immediately and be continued for at least 6 months after the patient's iron levels return to normal. Patients requiring transfusions should be placed onto iron, B12, and folate; although, their iron levels will need careful monitoring if they undergo subsequent transfusions, as they are at risk of iron toxicity.

Note that in many patients, especially menstruating women, a degree of mild anemia may not be rectifiable, and as long as this is asymptomatic then this should be tolerated.

Severe anemia from a young age may lead to chronic problems related to impaired neurological development. This is unlikely to be completely amenable to medical management, and in these cases, the focus should be on prevention.


Anemia if undiagnosed or left untreated for prolonged period of time can lead to multiorgan failure and can even lead to death. Pregnant women with anemia can go into premature labour and low birth weight babies[0]. Complications are more predominant in older population due to multiple comorbidities [0].


Gastroenterologist if GI bleed suspected. Nephologist if anemia of chronic disease suspected. Hematologist if bone marrow disorders suspected. Gynecologist if menorrhagia suspected.

Deterrence and Patient Education

Patients should be educated on the cause of their anemia, and simple lifestyle modifications that may help with this. For instance, in vegan and vegetarian patients, supplemental iron may be needed for long-term relapse prevention.

Pearls and Other Issues

Always send blood films in patients with unclear etiology of anemia.

Start haematinics early (iron, B12, and folate).

Inform patients of the side effects of iron therapy, including constipation and black stools.

Consider screening for sickle cell and thalassemia in patients with unexplained anemia or with a family history of these diseases.

Vitamin C aids iron absorption, so coadministration of vitamin C with iron, or encouraging the patients to take iron supplements with orange juice, will aid therapy.

Enhancing Healthcare Team Outcomes

Anemia can be caused my multiple conditions as mentioned above. Identifying cause and treating appropritely is very crucial in management of anemia. This need a good team work between patient, patient's primary care physicians and consultant physician based on the cause (Gastroenterologist, Nephrologist, Hematologist or Gynecologist). Taking all necessary medications along with lifestyle modifications and frequent follow up with team of doctors is important to prevent development of complications. 


[1] Bengi G,Keyvan H,Durmaz SB,Akpınar H, Frequency, types, and treatment of anemia in Turkish patients with inflammatory bowel disease. World journal of gastroenterology. 2018 Sep 28     [PubMed PMID: 30271083]
[4] Engebretsen KV,Blom-Høgestøl IK,Hewitt S,Risstad H,Moum B,Kristinsson JA,Mala T, Anemia following Roux-en-Y gastric bypass for morbid obesity; a 5-year follow-up study. Scandinavian journal of gastroenterology. 2018 Aug     [PubMed PMID: 30231804]
[5] Badireddy M,Baradhi KM, Chronic Anemia 2018 Jan;     [PubMed PMID: 30521224]
[6] Amin SK,Antunes C, Gastrointestinal Bleeding, Lower . 2018 Jan     [PubMed PMID: 28846221]