Definition

Anaemia is functionally defined as the presence of insufficient red blood cells mass to adequately deliver the oxygen to the peripheral. According to World Health Organization haemoglobin of less than 13.0 g/dL in an adult male, less than 12.0 g/dL in adult non pregnant female and less than 11.0 g/dL in pregnant female should be considered as evidence of anaemia.

Normal Haemogram Values

Kinetic Classification

Kinetic classification of anaemia based on reticulocyte production index (RPI) is most relevant clinically. Anaemias can be categorized as either hypoproliferative or hyperproliferative. Hypoproliferative  anaemia are due to impaired RBC production and result from acquired nutritional deficiencies or systemic disease. Hyperproliferative anaemias may be either congenital or acquired, the former being more common in children and the latter in adults.

Clinical Features

Anaemia is never seen in normal person. The signs and symptoms of anaemia will depend on how rapidly it develops its severity and age of the patient. Patient with anaemia usually seeks medical attention because of decreased work or exercise tolerance, shortness of breath, palpitation or fatiguability. In elderly individuals with cardiovascular disease, angina and heart failure may be precipitated. Systolic murmurs are common cardiac sign associated with anaemia. Systolic murmurs are best heard in pulmonary area. The pallor of skin and mucous membrane is a sign of anaemia. Skin and mucosal changes especially in nails and hairs are very common with anaemia. The nails may lose their lustre , become brittle and break easily commonly noticed in chronic iron deficiency anaemia. Headache, faintness, lack of mental concentration, tinnitus and vertigo are common symptoms of severe anaemia.

Diagnosis of Anaemia

The correct diagnosis of anaemia requires a thorough history and physical examination along with complete blood cell count, reticulocyte count, and peripheral blood smear.

i) History and physical examination

A careful history and physical examination will provides clues to the potential cause, as well as underlying systemic disorders like renal failure, diabetes mellitus, malignancy etc.

Dietary history is very important particularly in the young with food-fads and the elderly with anaemia. Drug history is necessary to rule out drug induced bone marrow depression or autoimmune haemolytic anaemia. A past history of gastrectomy or ileal resection may point towards deficiency anaemia. Menstrual or reproductive history is important to assess the iron status. Occupational history may be relevant in the patients exposed to welding, paints, dyes resulting in exposure to lead or other potentially marrow toxic agents. A family history of anaemia, jaundice, gall stones or splenectomy may hint towards the inherited haemolytic anaemia.

On examination, the pallor of the skin may be accompanied by angular cheilities and koilonychia in iron deficiency anaemia and hyperpigmentation of knuckles in megaloblastic anaemia. Presence of jaundice along with pallor would suggest the possibility of haemolytic anaemia. Splenomegaly in adults may indicate an aquire disorder like AIHA, infections like kala-azar, venous congestion or lymphoproliferative or myeloproliferative disorders. There may be exquisite tenderness over the bones specially over sternum suggesting acute leukaemia. The patient presenting with neurological findings, such as loss of vibration or position sense in the extremities should be investigated for early changes of megaloblastic anaemia even in absence of marked reduction of Hb.

ii) Reticulocyte count

The reticulocyte count provides important information about the dynamics of the RBC production as a result of anaemia, and helps in classification and guiding the initial investigation of anaemia. The reticulocyte count can be done manually using supravital stains, or more accurately by automated cell counters and flow cytometers using fluorescent dyes.

iii) Red cell indices

Automated cell counters provides detailed information regarding size, shape and Hb content of RBCs. Mean corpuscular volume in femtoliters and the RBC distribution width are the two important parameters useful in classifying the anaemia. These parameters are useful because relatively reproducible changes in the MCV and RDW are associated with certain types of anaemia.

iv) Peripheral blood smear

Despite the availability of automated cell counters and sophisticated diagnostic testing, the review of well made peripheral blood smear remains one of the most informative and rewarded diagnostics procedure. Only the blood smear reveals the unique morphologic changes occurring with various haemolytic disorders. Microcytic, hypochromic red cells are suggestive of iron deficiency anaemia or thalassaemia whereas macrocytic red cells with ovalocytes are suggestive of megaloblastic anaemia. Target cells may be seen in the cases of liver disease, as well as haemoglobinopathies, including sickle cell disease or thalassaemia.

v) Bone marrow examination

Bone marrow aspiration and biopsy allow for the examination of cellular morphology and marrow architecture, respectively. It is generally avoided in the initial work-up of anaemia because of discomfort involved in the procedure and minimal additional information. It becomes necessary in cases where the possibility of myelodisplasia, leukaemia, or lymphoma is being considered. Bone marrow biopsy is indicated to rule out aplastic anaemia.

vi) Additional tests in work-up of Anaemia

a) Haemolytic work-up
    - Cation exchange Hb-HPLC/Hb electrophoresis, sickling test, coomb’s test, osmotic red cell fragility, test for cold agglutinins.

b) Iron, vitamin B₁₂& folic acid
    - serum iron, iron-binding capacity, transferrine saturation, serum ferritin, marrow iron and serum trasferrine receptors help in differenciating iron deficiency & anaemia due to chronic disorders. Vitamin B₁₂ and folate levels may be estimated in suspected megaloblastic anaemia along with metabolites like homocysteine and methylmalonic acid.

c) Urine and stool examination
    - urine examination for proteins, pus cells, red cells, urobillinogen, and haemosiderin can provide information for anaemia. Stool examination for ova, cyst, and occult blood should be done in iron deficiency anaemia.

Prevention

a proper dietary guidance and balanced diet is the most important factor in preventing occurrence of nutritional anaemias. In addition routine antenatal screening and detection programs should be placed to reduce burden of thalassaemia major and other haemoglobinopathies in society. A detailed history, CBC, and a peripheral blood smear facilitate an efficient diagnosis and lower the chances of unnecessary testings.