"...all doctors should be able to diagnose and treat nutritional deficiencies."

Royal College of Physicians. Nutrition and Patients: A Doctor's Responsibility. London 2002

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Severe Anaemia

Anaemia is a common medical problem and can be due to deficiency of one or more nutrients, blood loss or a variety of medical problems.  As a general rule anaemia of almost any degree requires medical assessment so that the correct cause can be ascertained and appropriate treatment given.

Worldwide anaemia is a major problem affecting approximately one quarter of the world’s population and is most often due to iron deficiency.  Anaemia, from any cause has profound effects on energy level, quality of life and often upon child development.

In developed countries including the UK many millions of people have mild anaemia, which is often due to dietary inadequacy and nutritional deficiencies. 

Severe anaemia is important because it indicates that there may be one or more serious nutritional deficiencies or an underlying medical problem that requires thorough assessment and treatment.

Anaemia Due to Nutritional Deficiencies

Anaemia is very often due to a lack of one or more of three main nutrients – iron, folate and vitamin B12.  Occasionally other nutritional deficiencies may also cause anaemia and each deficiency results in different changes to the red cells making them smaller – microcytic, or larger – macrocytic, paler – hypochromic, or of normal colour – normochromic.  

Nutrient Type of Anaemia Other Features of Deficiency
Iron Microcytic hypochromic red cells and neutrophil hypersegmentation is also possible Low iron stores in bone marrow
Folate Macrocytic anaemia with hypersegmentation of the neutrophils Megaloblastic bone marrow, and a reduced serum vitamin B12
Vitamin B12 Macrocytic anaemia with hypersegmentation of the neutrophils.  Neutropenia and thrombocytopenia may also occur Megaloblastic bone marrow or bone marrow suppression with pancytopenia. Raised serum folate and reduced red cell folate is also possible
Vitamin C Iron deficiency picture or a macrocytic anaemia Reduced iron absorption, increased risk of bruising or bleeding or impairment of folate metabolism
Vitamin A Normochromic normocytic anaemia or iron deficient picture.  Anaemia has been observed in experimental adult vitamin A deficiency Reduced iron absorption, transport, delivery to the bone marrow and reduced production of erythropoietin
Vitamin B2 – riboflavin Normochromic, normocytic anaemia in severe deficiency.  Deficiency is associated with more iron deficiency but not anaemia Mechanism of anaemia is uncertain.  Minor perturbations in riboflavin metabolism may be common in beta-thalassaemia heterozygotes
Vitamin B3 Normochromic normocytic anaemia in case reports.  Lymphopenia and eosinopenia also reported Protein-energy malnutrition may be present. Iron deficiency reduces conversion of tryptophan to nicotinamide
Copper Hypochromia, normocytic, macrocytic or rarely macrocytic red cells, neutropenia and thrombocytopenia Megaloblastic bone marrow changes, ringed sideroblasts and normal iron stores indicating defective iron mobilization.  Reduced iron absorption may also occur
Zinc Anaemia possibly secondary to chronic infection in severe zinc deficiency Poor immune function, poor night vision and loss of appetite 

What is Severe Anaemia

According to Clinical Knowledge Summaries, the NHS funded resource that provides expert guidance for common conditions, iron deficiency anaemia that requires urgent attention includes:

  • Men of any age with unexplained iron deficiency anaemia and a haemoglobin level of 11 g/dl or below – refer urgently (within 2 weeks) to a gastroenterologist
  • Women, who are not menstruating, with an unexplained iron deficiency anaemia and a haemoglobin level of 10 g/dl or below – refer urgently (within 2 weeks) to a gastroenterologist
  • People of any age with dyspepsia who present with iron deficiency anaemia – refer urgently (within 2 weeks) for endoscopy or to a specialist with expertise in upper gastrointestinal cancer
  • People with iron deficiency anaemia without dyspepsia – recognise the possibility of upper gastrointestinal cancer and consider urgent referral for further investigation
  • People with unexplained iron deficiency anaemia who do not fulfil these criteria for urgent referral will still require referral for further investigation.  The urgency of this will require clinical judgement based upon the haemoglobin level and clinical findings.

Other situations that will also require referral to appropriate specialist include:

  • Profound anaemia and heart failure
  • Anaemia due to menorrhagia that fails to respond to treatment
  • Those who are truly intolerant of oral iron supplements
  • Those with anaemia without an obvious and non-sinister cause that fails to respond to treatment or is recurrent

Symptoms and Signs of Anaemia

People vary considerably in their propensity to anaemia and the symptoms that they may experience as a result of becoming anaemic.  Common symptoms of anaemia regardless of the cause include:

  • fatigue
  • lethargy
  • shortness of breath on exercise
  • palpitations
  • sore tongue
  • recurrent mouth ulceration
  • headache
  • loss or change in appetite

Common outward signs of anaemia include:

  • pale appearance
  • changes in the appearance of the tongue, which may have a smooth appearance
  • cracking at the corners of the mouth - angular stomatitis
  • fingernails that are spoon-shaped, easily split or brittle
  • mild diffuse loss of scalp hair in women - alopecia
  • other signs relating to deficiency of folate, vitamin B12 and iron

Tests for Anaemia

The standard test for anaemia is a Full Blood Count, which assess the level of haemoglobin and makes other measures of red cells and white cells which gives important clues as to the possible cause(s) of the anaemia and other information.

Haemoglobin is the iron-rich pigment that carries oxygen from the lungs to the tissues and is found in the red blood cells.  The concentration of haemoglobin varies across the lifespan. 

The World Health Organisation has established normal ranges for children, adults and pregnant women as given in the tables below with adjustments for those who are smoking or living at higher altitude.                                                                    

Haemoglobin and Haematocrit Levels Below which Anaemia is Present in a Population

Age or gender group
Haemoglobin g/dl
Haematocrit mmol/l
l/l
Children 6 months to 59 months
11.0
6.83
0.33
Children 5-11 years
11.5
.13;
0.34
Children 12-14 years
12.0
7.45
0.36
Non-pregnant women
(above 15 years of age)
12.0
7.45
0.36
Pregnant women
11.0
6.83;
0.33
Men (above 15 years of age)
13.0
8.07
0.39

Normal Gestation-Related Changes of Haemoglobin and Haematocrit Values

Gestation (weeks)
12
16
20
24
28
32
36
40
Haemoglobin (g/dl) Mean 12.2 11.8 11.6 11.6 11.8 12.1 12.5 12.9
-2SD (lower end of normal) 10.8 10.4 10.3 10.3 10.5 10.8 11.2 11.6
Haematocrit (l/l) Mean 0.367 0.354 0.348 0.348 0.355 0.364 0.375 0.387
-2SD (lower end of normal) 0.325 0.315 0.310 0.310 0.315 0.325 0.335 0.350

Normal Increases of Haemoglobin and Haematocrit Values Related to Long-Term Altitude Exposure

Altitude (metres) Increase in haemoglobin (g/dl) Increase in haematocrit (l/l)
<1000 0 0
1000 +0.2 +0.005
1500 +0.5 +0.015
2000 +0.8 +0.025
2500 +1.3 +0.040
3000 +1.9 +0.060
3500 +2.7 +0.085
4000 +3.5 +0.110
4500 +4.5 +0.140

Adjustments for Haemoglobin and Haematocrit Values for Smokers

 
Haemoglobin (g/dl)
Haematocrit (l/l)
Non-smoker
0
0
Smoker (all)
+0.3
+0.010
½ - 1 packet/day
+0.3
+0.010
1-2 packets/day
+0.5
+0.015
+2 packets/day
+0.7
+0.020

References:

Iron Deficiency Anaemia: Assessment, Prevention and Control.  A Guide for Programme Managers www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf
www.cks.library.nhs.uk/anaemia_iron_deficiency/view_whole_topic_review
Nutritional Anaemia.  Book Eds: Kraemer K, Zimmerman MB. 2007 http://www.sightandlife.org/pdf/NAbook.pdf
Spivak JL, Jackson DL. Pellagra: an analysis of 18 patients and a review of the literature.  John Hopkins Med J. 1977Jun;140(6):295-309  www.ncbi.nih.gov/pubmed/864902?

General Causes of Anaemia

There are many possible causes and only the main ones are detailed here:

  • Dietary inadequacy of iron, vitamin B12 or folate are all possible causes with dietary lack of iron being particularly common in infants, children and menstruating women
  • Heavy periods result in approximately 10% of menstruating women being anaemic or having mild iron deficiency as their intake can barely keep pace with demand.  The oral contraceptive pill reduces menstrual bleeding and the risk of anaemia developing.  All women with troublesome heavy periods should be assessed
  • Pregnancy often results in mild anaemia due to the high demands of the growing foetus especially in the last 20 weeks and a supplement of iron with folic acid is often given
  • Gastrointestinal blood loss is a common cause especially in older people but can occur at any age.  Possible causes include use of aspirin – even at low dose, non-steroidal anti-inflammatory drugs,  stomach ulcer and cancer of the stomach, colon and rarely elsewhere
  • Malabsorption especially coeliac disease or any gastrointestinal disease resulting in reduced absorption of iron and sometimes vitamin B12 or folate
  • Chronic disorders including diseases affecting the bone marrow, chronic inflammatory disease (e.g. rheumatoid arthritis or chronic infection), endocrine disorders (e.g. hypothyroidism, hypopituitarism and hypoadrenalism) and renal failure
  • Old age may be considered a cause as haemoglobin levels routinely fall in the very elderly >85 years.  This is often due to a deteriorating diet and one or more of the above problems.  Additionally in elderly men a small fall in haemoglobin seems to be related, in part, to the natural fall in testosterone and may be considered normal but only after treatable causes have been excluded. 

As a general rule, haemoglobin levels below 10 g/dl in men or women of any age always require detailed investigation

Prevalence of Anaemia and Related Nutrient Deficiencies in British People

                               
Men
Women
  15-18yrs 19-64yrs 65-84yrs >85yrs 15-18yrs 19-64yrs 65-84yrs >85yrs
Anaemia
Haemoglobin <12.0/13.0g/dl
1% 3% 9% 37% 9% 8% 8% 16%
Severe Anaemia
Haemoglobin <11/10g/dl
0 <1% 1% 11% <1% <1% 1% 1%
Iron Deficiency
Iron saturation <15%
12% 7% 5% 15% 30% 16% 13% 16%
Folate Deficiency
Red cell folate <350nmol/l
12% 5% 27% 30% 14% 5% 28% 34%
Vitamin B12 Deficiency
Plasma B12 <118pmol/l
1% 2% 7% 10% 8% 4% 4% 10%
Vitamin C Deficiency
Plasma Vitamin C <11.0umol/l
3% 5% 12% 20% 4% 3% 12% 18%

 



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