Anaemia

Last updated: January 2024

 

Anaemia is defined as a haemoglobin (Hb) level below reference values [1] Citation 1. World Health Organization. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. World Health Organization; 2011. [Accessed June 26, 2023]
https://apps.who.int/iris/handle/10665/85839 [2] Citation 2. World Health Organization. Educational Modules on Clinical Use of Blood. World Health Organization; 2021. [Accessed June 26, 2023]
https://apps.who.int/iris/handle/10665/350246 , which vary depending on age, sex, and pregnancy status (see Table 2).

 

Anaemia may be caused by:

• Decreased production of red blood cells: iron deficiency, nutritional deficiencies (folic acid, vitamin B₁₂, vitamin A), depressed bone marrow function, certain infections (HIV, visceral leishmaniasis), renal failure;
• Loss of red blood cells: acute or chronic haemorrhage (gastrointestinal ulcer, ancylostomiasis, schistosomiasis, etc.);
• Increased destruction of red blood cells (haemolysis): parasitic (malaria), bacterial and viral (HIV) infections; haemoglobinopathies (sickle cell disease, thalassaemia); intolerance to certain drugs (primaquine, dapsone, co-trimoxazole, nitrofurantoin, etc.) in patients with G6PD deficiency.

 

The causes of anaemia are often interlinked.

Clinical features

• Common signs: pallor of the conjunctivae, mucous membranes, palms of hands and soles of feet; fatigue, dizziness, dyspnoea, tachycardia, heart murmur.
• Signs of decompensation: cold extremities, altered mental status, oedema in the lower limbs, respiratory distress, elevated jugular venous pressure, cardiac/coronary failure, shock.
• Significant signs: cheilosis and glossitis (nutritional deficiency), jaundice, hepatosplenomegaly, dark coloured urine (haemolysis), bleeding (maelena, haematuria, etc.), signs of malaria (Chapter 6), etc.

Laboratory

• Hb levels
• Rapid diagnostic test or thick and thin blood films in areas where malaria is endemic.
• Urinary dipstick: check for haemoglobinuria or haematuria.
• If sickle cell disease is suspected (to be done before blood transfusion): rapid diagnostic test (Sickle SCAN®) or, if not available, Emmel test.
• Full blood count (FBC) if available to guide diagnosis.

 

Table 1 - Possible diagnoses with FBC

 

Characteristics	Main diagnoses
Macrocytic	Deficiency (folic acid, vitamin B12), chronic alcoholism
Microcytic	Iron deficiency (malnutrition, chronic haemorrhage), chronic inflammation (HIV infection, cancer), thalassaemia
Normocytic	Acute haemorrhage, renal failure, haemolysis
Reduced number of reticulocytes	Deficiency (iron, folic acid, vitamin B12), spinal tumour, renal failure
Increased or normal number of reticulocytes	Haemolysis, sickle cell disease, thalassaemia
Eosinophilia	Ancylostomiasis, trichuriasis, schistosomiasis, HIV infection, malignant haemopathies

 

Aetiological treatment

Anaemia in itself is not an indication for transfusion. Most anaemias are well tolerated and can be corrected with simple aetiological treatment.
Aetiological treatment may be given alone or together with transfusion.

• Iron deficiency

ferrous salts/folic acid PO, or if not available, ferrous salts PO, for 3 months

Doses are expressed in elemental iron a Citation a. A coformulated tablet of ferrous salts/folic acid contains 185 mg of ferrous fumarate or sulfate (equivalent to 60 mg of elemental iron) and 400 micrograms of folic acid.
A 200 mg tablet of ferrous fumarate or sulfate contains 65 mg of elemental iron.
A 140 mg/5 ml syrup of ferrous fumarate contains 45 mg/5 ml of elemental iron. :

• Children 1 month to < 6 years: 1.5 to 3 mg/kg 2 times daily
• Children 6 to < 12 years: 65 mg 2 times daily
• Children ≥ 12 years and adults: 65 mg 2 to 3 times daily

 

Age	Weight	Treatment
		45 mg/5 ml syrup	60 or 65 mg tablet
1 month to < 1 year	4 to < 10 kg	1.5 ml x 2	–
1 to < 6 years	10 to < 20 kg	2.5 ml x 2	–
6 to < 12 years	20 to < 40 kg	–	1 tab x 2
≥ 12 years and adults	≥ 40 kg		1 tab x 2 or 3

 

• Helminthic infections: see Schistosomiasis and Nematode infections (Chapter 6).
• Folic acid deficiency (rarely isolated)

folic acid PO for 4 months:

• Children under 1 year: 0.5 mg/kg once daily
• Children 1 year and over and adults: 5 mg once daily

• Malaria: see Malaria (Chapter 6). In the event of associated iron deficiency, wait 4 weeks after malaria treatment before prescribing iron supplements.
• Suspected haemolytic anaemia: stop any drug that causes haemolysis in patients with (or that may possibly have) G6PD deficiency.

Blood transfusion

Indications

To decide whether to transfuse, several parameters should be taken into account:

• Clinical tolerance of anaemia
• Underlying conditions (cardiovascular disease, infection, etc.)
• Rate at which anaemia develops.
• Hb levels

If transfusion is indicated, it should be carried out without delay b Citation b. Before transfusing: determine the recipient’s and potential donors’ blood groups/rhesus and carry out screening tests on the donor’s blood for HIV-1 and 2, hepatitis B and C, syphilis and, in endemic areas, malaria and Chagas disease. . For transfusion thresholds, see Table 2.

Volume to be transfused

If presence of haemorrhagic shock: see Shock, Chapter 1. Otherwise:

 

• Children [3] Citation 3. Maitland K, Olupot-Olupot P, Kiguli S, et al. Transfusion Volume for Children with Severe Anemia in Africa. N Engl J Med. 2019;381(5):420-431.
  https://doi.org/10.1056/NEJMoa1900100 :

Transfusion volume is based on presence or absence of fever at any point from the time of ordering blood to the time of transfusion: 

• If no fever (axillary temperature ≤ 37.5 °C) c Citation c. Axillary temperature should be taken at the time of ordering blood and immediately prior to transfusion. : administer either 15 ml/kg of packed red blood cells (PRBC) over 3 hours or 30 ml/kg of whole blood over 4 hours
• If fever (axillary temperature > 37.5 °C) c Citation c. Axillary temperature should be taken at the time of ordering blood and immediately prior to transfusion. : administer either 10 ml/kg of PRBC over 3 hours or 20 ml/kg of whole blood over 4 hours

 

• Adolescents and adults: start with an adult unit of PRBC or whole blood; do not exceed a transfusion rate of 5 ml/kg/hour.

 

Repeat if necessary, depending on clinical condition.

Monitoring

• Monitor the patient’s condition and vital signs (heart rate, blood pressure, respiratory rate, temperature):
  • During the transfusion: 5 minutes after the start of transfusion, then every 15 minutes during the first hour, then every 30 minutes until the end of the transfusion.
  • After the transfusion: 4 to 6 hours after the end of the transfusion.
• Pay attention to signs of transfusion reaction, fluid overload, decompensation or continuing blood loss.
• For children: measure Hb once between 8 and 24 hours after the end of the transfusion or if signs of decompensation or continuing blood loss.
• If signs of circulatory overload appear:
  • Stop temporarily the transfusion.
  • Sit the patient in an upright position.
  • Administer oxygen.
  • Administer furosemide by slow IV injection:
    • Children: 0.5 to 1 mg/kg
    • Adults: 20 to 40 mg

Repeat the injection (same dose) after 2 hours if necessary.

• Once the patient has been stabilised, start the transfusion again after 30 minutes.

Prevention

• Iron (and folic acid) deficiency:
  • Drug supplements:

ferrous salts/folic acid PO, or if not available, ferrous salts PO, as long as the risk of deficiency persists (e.g. pregnancy [4] Citation 4. Word Health Organization. Daily iron and folic acid supplementation in pregnant women. Word Health Organization. Geneva, 2012. [Accessed June 26, 2023]
https://apps.who.int/iris/handle/10665/77770 , malnutrition).

Doses are expressed in elemental iron a Citation a. A coformulated tablet of ferrous salts/folic acid contains 185 mg of ferrous fumarate or sulfate (equivalent to 60 mg of elemental iron) and 400 micrograms of folic acid.
A 200 mg tablet of ferrous fumarate or sulfate contains 65 mg of elemental iron.
A 140 mg/5 ml syrup of ferrous fumarate contains 45 mg/5 ml of elemental iron. :

• Children 1 month to < 12 years: 1 to 2 mg/kg once daily (max. 65 mg daily)
• Children ≥ 12 years and adults: 65 mg once daily

​​

Age	Weight	Prevention
		45 mg/5 ml syrup	60 or 65 mg tablet
1 month to < 1 year	4 to < 10 kg	1 ml	–
1 to < 6 years	10 to < 20 kg	2.5 ml	–
6 to < 12 years	20 to < 40 kg	5 ml	–
≥ 12 years and adults	≥ 40 kg	–	1 tab

 

• Nutritional supplements (if the basic diet is insufficient).

 

• In the event of sickle cell anaemia: see Sickle cell disease (Chapter 12).
• Early treatment of malaria, helminthic infections, etc.

 

Table 2 - Definition of anaemia and transfusion thresholds

 

Patients	Hb levels defining anaemia	Transfusion thresholds
Children 2-6 months	< 9.5 g/dl	Hb < 4 g/dl, even if there are no signs of decompensation Hb ≥ 4 g/dl and < 6 g/dl if there are signs of decompensation or ongoing blood loss or severe malaria or serious bacterial infection or pre-existing heart disease (a) Citation a. Immediate transfusion is not required in children 2 months to 12 years with Hb ≥ 4 g/dl and < 6 g/dl and no sign of decompensation or ongoing blood loss, provided that: • they are closely monitored (including Hb measurements at 8, 24 and 48 hours), and • transfusion preparation (blood grouping, etc.) is carried out without delay in case the child needs to be transfused later on.
Children 6 months-4 years	< 11 g/dl
Children 5-11 years	< 11.5 g/dl
Children 12-14 years	< 12 g/dl
Men (≥ 15 years)	< 13 g/dl	Hb < 7 g/dl if there are signs of decompensation or ongoing blood loss or severe malaria or serious bacterial infection or pre-existing heart disease
Women (≥ 15 years)	< 12 g/dl
Pregnant women	< 11 g/dl (1st and 3rd trimester)   < 10.5 g/dl (2nd trimester)	< 36 weeks Hb ≤ 5 g/dl, even if there are no signs of decompensation Hb > 5 g/dl and < 7 g/dl if there are signs of decompensation or sickle cell disease or severe malaria or serious bacterial infection or pre-existing heart disease
		≥ 36 weeks Hb ≤ 6 g/dl, even if there are no signs of decompensation Hb > 6 g/dl and < 8 g/dl if there are signs of decompensation or sickle cell disease or severe malaria or serious bacterial infection or pre-existing heart disease