practical approach to anaemia Flashcards
define anaemia
Reduction in the red cell mass or haemoglobin to a level which is insufficient to meet the body’s physiological needs
general mechanisms of anaemia
Defective production of red cells by marrow
Defective proliferation of erythroid precursors
Defective maturation of erythroid precursors
Both of above
Increased rate of red cell destruction (haemolysis)
Increased loss of red cells from circulation (bleeding)
mechanism of anaemia in End stage renal disease
End stage renal disease:
Erythropoietin deficiency
Marrow suppression from uraemia
Increased bleeding from platelet dysfunction
Folate loss during haemodialysis
Haemolysis from marrow suppression & haemodialysis
mechanism of anaemia in crohn’s disease
Crohn’s disease: Anaemia of chronic disease Iron deficiency from bleeding Folate and B12 deficiency Drug treatment – azathioprine, sulfasalazine, methotrexate etc
how is anaemia classified
Anaemia can be classified as follows:
1. By specific cause – eg. iron deficiency anaemia, folate deficiency anaemia.
2. By the morphological abnormalities on the blood film or bone marrow
a. Normocytic (normal sized red cells)
b. Microcytic (small red cell cells)
c. Macrocytic (large red cells)
d. Hypochromic (pale red cells)
e. Megaloblastic (erythroid precursor cells in the marrow with a distinctive morphological appearance)
f. Leucoerythroblastic (denotes the presence of both precursor white and red cell blood cells on a stained blood film)
3. By the underlying pathophysiological process – eg. haemolytic anaemia, aplastic anaemia
Describing anaemia by size of the red cells is the usual method of classifying an undiagnosed anaemia.
Microcytic hypochromic anaemia
Iron deficiency
Thalassaemia syndromes
Anaemia of chronic disease
Sideroblastic anaemia
Macrocytic anaemia
Megaloblastic anaemia :(megaloblastic erythropoiesis)
B12 and folate deficiency
Non-megaloblastic causes: (normoblastic erythropoiesis) Alcohol Liver disease Reticulocytosis Hypothyroidism Cytotoxic drugs Haematological disease (eg. MDS, aplastic anaemia) Other
Normocytic normochromic anaemia
Anaemia of chronic disease
- Chronic infection
- Inflammatory disease (non-infective)
- Malignant disease etc
Chronic kidney disease
Bone marrow failure
Acute blood loss
Other
Key principles of investigation of anaemia
- Full blood count
a. Is the anaemia normocytic, microcytic or normocytic? Helps to narrow
down list of possible causes
b. Are there any other abnormalities of the blood count?
2. Blood
a. Extremely important in the investigation of haematological
abnormalities
b. Morphology of red cell, white cells, platelets
c. Any other abnormalities? (eg. blasts would suggest acute leukaemia)
- Haematinics – serum B12, folate and iron studies
- Biochemistry – U&Es, LFTs, inflammatory markers (if indicated)
initial investigations in anaema
The general approach to investigating iron deficiency (and B12 and folate deficiency) is first to confirm the presence of iron deficiency, then to investigate to find its cause.
Full blood count:
Is it normocytic, microcytic or macrocytic?
Are there other abnormalities – neutropenia, thrombocytopenia ?etc
Blood film:
Red cell morphology – size, shape, other
White cell and platelet morphology
Other (eg. blasts)
Haematinics:
Serum B12, folate, iron studies
.Serum iron, total iron binding capacity (TIBC) and ferritin
a. typical pattern in iron deficiency is LOW serum iron, INCREASED TIBC, and LOW serum ferritin. Note that serum ferritin is an acute phase protein and is therefore raised in acute illness even when iron deficiency is present
b. Transferrin saturation is LOW in iron deficiency – it can be derived from the serum and TIBC or measured directly
Biochemistry:
U&Es
LFTs
where does erythropoieisis occur
In pre-natal life, the liver and spleen are important sites of erythropoiesis. After birth, the bone marrow becomes the sole site of normal erythropoiesis; erythropoiesis that occurs in any other site is abnormal. In children, all sites of the skeleton are involved, but in adults erythropoiesis is limited to the axial skeleton and proximal ends of the femora and humerii. The bone marrow is one of the largest organs in the body and also one of the most active.
process of erythropoiesis
The total maturation time of red cells precursors in the marrow is approximately 7 days. The first 4 days are spent in cell division and the remaining 3 days in maturation and haemoglobin synthesis.
The nucleus is extruded from the developing erythroid precursors to form young red cells called reticulocytes. Reticulocytes remain in the marrow for a further 24 hours, then move into the peripheral circulation where they mature into red cells in approximately 1 day. The life span of mature red cells is around 120 days. Approximately 1% of the total red cell mass is destroyed daily, approximately the same number of reticulocytes enter the circulation daily.
where are reticulocytes found
Erythroid precursors reside in the marrow compartment, with the exception of young red cell known as reticulocytes which occur in small numbers in the peripheral blood compartment (up to about 2% of the red cell population). The presence of earlier erythroid precursors or of increased numbers of reticulocytes in the peripheral blood is abnormal and denotes a pathological state.
normal lifespan of a RBC
120 days. destroyed by macrophages principally in the spleen. bilirubin is produced. transported to liver by serum haptoglobins for metabolism. conjugated bilirubin excreted in bile.
stages of deficiency anaemias
Stages of deficiency
Deficiency states develop in the following order: depletion of tissue stores, development of morphological abnormalities on the blood film and marrow, and anaemia. Note that anaemia is the final expression of the deficiency state. Symptoms and serious complications may be evident before the development of anaemia. It is therefore imperative to investigate and correct the deficiency even when the haemoglobin concentration is normal.
The order is reversed during treatment, with normalisation of the haemoglobin concentration and morphological features ahead of replenishment of tissue stores. It is therefore important to continue replacement treatment for long enough to ensure that tissue stores are replete.
Causes of iron deficiency
- Reduced dietary intake – diets lacking in red meat and green vegetables
- Reduced absorption – causes include coeliac disease, gastrectomy
- Chronic blood loss – any cause of chronic blood loss
a. Menorrhagia is the commonest cause in UK
b. Blood loss from the gastrointestinal tract is also very common. Causes
include peptic ulcers and stomach and colon cancer. Malignancy should be excluded in older patients and patients with a family history of bowel cancer presenting with unexplained iron deficiency
c. Hookworm is commonest cause worldwide - Increased physiological demands where iron stores are borderline and intake
is not sufficient to cope with the increased requirements – pregnancy, prematurity, adolescent growth spurt
Clinical features of iron deficiency
- General symptoms of anaemia – tiredness, exertional dyspnoea etc
- Features of tissue deficiency include
a. angular stomatitis – sore areas at the corners of the mouth
b. koilonychias – brittle, spoon-shaped nails
c. painful glossitis
d. atrophic glossitis
e. dysphagia as a result of pharyngeal web (rare)
f. irritability
g. cognitive impairment in children
Establishing the cause of iron deficiency
The general approach to investigating iron deficiency (and B12 and folate deficiency) is first to confirm the presence of iron deficiency, then to investigate to find its cause.\
Establishing the cause of iron deficiency
- This may be evident from the history – eg. history of poor dietary intake, menorrhagia, chronic blood loss from rectal bleeding, etc.
- Coeliac screen – anti-tissue glutaminase if coeliac disease is suspected. Duodenal biopsies are also diagnostic
- Gastroscopy and/or colonoscopy – in individuals with gastrointestinal symptoms, or with symptoms such as unexplained weight loss. Also in those with unexplained anaemia
- Capsule endoscopy – may be required to investigate possible occult bleeding in areas of the small bowel that are inaccessible to gastroscopy and colonoscopy
- Gynaecological investigations – transvaginal ultrasound, hysteroscopy etc for PV bleeding
- Stool for ova, cysts and parasites – hookworm, schistosomiasis etc. A positive travel history may be relevant
steps of treatment of iron deficiency
This involves:
- Correction of the iron deficiency
- Treatment of the underlying cause
Correction of iron deficiency
Oral iron: The most cost effective treatment is oral iron supplementation, most commonly with ferrous sulphate. The recommended therapeutic dose is 200mg three times daily. It is generally well tolerated and will correct anaemia and morphological abnormalities, and will restore tissue stores if given for a period of several months (eg. 4-6 months). Equally effective alternative preparations including liquid formulations of iron are also available.
Oral iron can cause gastrointestinal side effects notably abdominal bloating and constipation, but diarrhoea may also occur. Some patients are unable to tolerate oral iron because of these side effects.
Poor response to oral iron – causes
- Poor compliance – commonest reason
- Malabsorption
- Wrong diagnosis – (eg. thalassaemia trait being misdiagnosed as iron deficiency)
4.Uncontrolled bleeding – where iron loss outstrips supply
Parenteral iron: Iron replacement may be given parenterally by intravenous infusion. Parenteral iron is indicated when oral iron cannot be tolerated or is ineffective. The main advantage of intravenous iron over oral preparations is that the entire treatment can be given within a day (depending on the product used), compared to several months for oral iron. There is no difference between intravenous iron and oral iron in terms of haemoglobin rise – the rate of rise of haemoglobin is identical for both routes. The main side effect of intravenous iron is anaphylaxis which is rare.
Differential diagnosis of microcytic, hypochromic anaemia
Iron deficiency
- by far the commonest cause in clinical practice in the UK
Thalassaemia syndromes
- this includes the different genotypes (eg. alpha and beta thalassaemia) and grades of severity – trait, intermediate and transfusion-dependent forms
- Beta thalassaemia trait – Hb usually >9g/dl and HbA2 is elevated in the majority of cases
- Note that people with thalassaemia can also become iron deficient; however, persisting microcytosis and hypochromia despite normal iron studies is suggestive of thalassaemia
Anaemia of chronic disease
- Usually normocytic, normochromic
- It is an abnormality of iron distribution where iron is sequestered in macrophages
instead of being released into the circulation
- Typical pattern is LOW serum iron, LOW TIBC and NORMAL OR RAISED serum
ferritin
Sideroblastic anaemia
- In sideroblastic anaemia the MCV may be low, normal or high.
- There is a defect in the incorporation of iron into haemoglobin. Iron therefore
accumulates in the mitochondria.
- Diagnostic feature is ring sideroblasts = marrow red cell precursors with a ring
of iron granules (mitochondria) surrounding the nucleus.
- This disorder may be primary, when it is classified as one of the myelodysplastic syndromes, or secondary to malignancy of any sort, alcohol, drugs, heavy metal poisoning and collagen diseases
