Anaemia / MORPHOLOGICAL/ ETIOLOGICALCLASSIFICATION/ Systemic Disease IN Anaemia.

Anemia

Anemia is not a specific disease. It is a condition in which oxygen carrying capacity of blood is reduced. Anemia is always a sign of an underlying disease, and never a diagnosis. A red cell count of less than 4.0 million/cu.mm (ul) in males and 3.5 million/cu.mm (ul) in females, or hemoglobin content of less than 10.8 g per 100 ml (108g/ L) in males and 9.5 g/100 ml (95 g/L) in females is an indication of anemia. Patients with anemia have similar

clinical symptoms

irrespective of the cause. Fatigue, breathlessness, dizziness and headache are some of the common complaints.

Anemia may be caused due to the following factors

• Increased haemolysis.
• Diminished erythropoiesis.
• Blood loss

Increased haemolysis may be due to hereditary defects such as spherocytosis, or sickle cells, which reduce the life span of the red cell; or may be acquired by the action of haemolytic agents. 

Diminished erythropoiesis is either due to a nutritional deficiency or due to the marrow failure. The nutritional factors essential for erythropoiesis are iron, cobalt, copper, vitamin B12, folic acid, pyridoxine, riboflavin, nicotinic acid, Vit C, proteins and some hormones. The deficiency of these factors may be dietetic, due to defective absorption or due to increased demands, (e.g., during pregnancy or period of growth).

Failure of marrow may be endogenous or due to extraneous toxic factors such as chemicals and drugs. Blood loss may be brought about by trauma or disease and may be acute or chronic in nature.

CLASSIFICATION OF ANEMIA

Generally, anemia are classified on the basis of the appearance of the red cells (morphological classification) or depending on the physiological cause (aetiological classification).

MORPHOLOGICAL CLASSIFICATION OF ANEMIA

Morphological classification of anemia depends on the examination of blood which includes the determination of hemoglobin, enumeration of red cells, red cell indices and the examination of the peripheral blood smear. 

The levels of hemoglobin and red cell count determine the severity of anemia while the examination of smear will give information about the size of the red cells, their hemoglobin content and presence of abnormal red cells. The red cell indices provide important guidelines for morphological classification of anemia.

 

1.Macrocytic, normochromic anemia:- MCV 100 to 160 cu.microns (FL) MCHC 32 to 36 %

Causes

(a) Deficiency of Vitamin B 2 or folic acid,hepatic disease, or antimetabolite drugs. The bone marrow shows abnormal red cell maturation, megaloblastic (increased red cell size) changes.

(b) Chronic liver disease, hypothyroidism etc. where bone marrow does not show abnormal megaloblastic changes.

2. Normocytic, Normochromic Anemia:- MCV 80 to 100 cu.um (fL), MCHC 32 to 36 %

Causes

(a) Sudden blood loss

(b) Haemolytic anaemias

(c) Haemoglobinopathies

 (d) Aplastic anaemia

3. Microcytic Normochromic Anemia:- MCV 69 to 80 cu.um (fL), MCHC 32 to 36 %

Causes

(a) Inflammatory conditions.

(b) Toxic drugs and chemicals

(c) Malignancy

(d) Endocrine disorders

4. Microcytic Hypochromic Anemia:- MCV 60 to 80 cu. um (FL), MCHC 20 to 30 %

Causes

(a) Iron deficiency due to blood loss, improper gastrointestinal absorption, excess demand.

(b) Miscellaneous, such as lead poisoning,thalassaemia.

5. Macrocytic Hypochromic Anemia:- MCV more than 100 cu. um (fL), MCHC less than 30 % Causes Deficiency of iron associated with deficiency of Vitamin B12 or folic acid.

ETIOLOGICAL CLASSIFICATION OF ANEMIA

1.Anemia Resulting from Excessive Destruction of Red Cells:- Due to intracellular defects Hereditary defects of red cell membrane (e.g. spherocytosis,

2.Autoimmune haemolytic anemia (AIHA) :-In AIHA, the defect is extracorpuscular. These anemia occur because of the production of antibodies against the patient's own red cells. The classification of their causes is shown in Table 5.3. The warm antibodies react better at 37°C while cold antibodies are active at 4°C. Warm AIHA Clinical features It is a haemolytic anemia of varying severity occurring at any age. The spleen is enlarged. Warm AIHA is frequently associated with other autoimmune disorders such as systemic lupus erythematosus (SLE).

Laboratory findings

1. Peripheral blood smear is typical of haemolytic anaemia and shows prominent spherocytosis.

2. Direct Coomb's test is positive.

3. Antibodies are best detected at 37°C.

Cold AIHA

Clinical features:-The patients have chronic haemolytic anaemia which increases in cold weather. Peripheral circulation (tip of the nose, ears, fingers, toes) may be affected due to agglutination of red cells in small vessels. Infections such as infectious mononucleosis or mycoplasma pneumonia may precipitate cold AIHA.

Iso-immune haemolytic anemia:- In this type of anaemia, antibodies produced by one person react with the red cells of another.

This can occur in: Transfusion of ABO incompatible blood 

(ii) Haemolytic disease of the new-born(HDN) 

1.Drug-induced immune haemolytic anaemia:- Many drugs can induce the formation of antibodies either against the drug itself or against red cell antigens. These antibodies, in the presence of complement, can bring about lysis of red cells. Drugs which are known to cause haemolytic anaemia include penicillin, cephalothin, phenacetin and methyl DOPA. Haemolytic anaemia gradually disappears when the drug is discontinued.

Paroxysmal nocturnal haemoglobinuria (PNH):-This occurs due to an acquired defect of the red cell membrane that makes it susceptible to complement mediated lysis of red cells. The defect is rare, haemolysis is intravascular and usually occurs at night (nocturnal). PNH is diagnosed by Ham's serum acid test (demonstration of red cell lysis at low pH). White cell, platelet and reticulocyte counts are low.

Paroxysmal cold haemoglobinuria (PCH):- This is similar to PNH but haemolysis occurs after exposure to cold. The patient's blood contains an antibody called Donath-Landsteiner antibody which binds red cells in the cold. The lysis with complement occurs at 37°C. Syphilis and viral infections are predisposing factors.

Classification of auto-immune hemolytic anaemias (AIHA)
Warm antibody	Cold antibody
A.    Idiopathic B.     Secondary to 1.systemic lupus-erthematous (SLE) 2. other auto_immune disease 3.chronic lymphatic leukemia(CLL) 4.lymphoma 5.drug such as methyl DOPA	A. Idiopathic . Secondary to   1.infection mononucleosis   2. mycoplasma pneumonia infection   3. lymphoma   4 .parxymal cold haemoglobinuria (RARE)

3.Miscellaneous haemolytic anemia:- Various causes other than those mentioned earlier can give rise to haemolysis and haemolytic anemia.

These include:

(I) Malaria.

(ii) Bacterial infections

(iii) Extensive burns.

(iv) Overdose with oxidizing drugs

(v) Chemical poisoning

(vi) Snake and spider bites.

4. Aplastic Anemia:-Aplastic anaemia results from aplasia of bone marrow. Haemopoiesis is affected causing reduction in the counts of all blood cell series (anaemia, leucopenia, thrombocytopenia, collectively called pancytopenia).

The causes of aplastic anaemia are divided into two groups:
(i) Primary causes	(ii) Secondary causes
(a) Congenital. (b) Idiopathic-without any obvious precipitating cause.	(a) Exposure to radiation such as radiotherapy, radioactive isotopes. (b) Chemicals: Organic solvents like benzene, hair dyes. (c) Drugs: Such as cyclophosphamide,

6 mercaptopurine, chloramphenicol.

(d) Infections: Viral hepatitis caused by hepatitis A virus and other related viruses.

Clinical features:- It can occur at any age, but is more common around 30 years of age. Infections, either localised (e.g. of the mouth and throat) or generalised, are very common. The lymph nodes, liver and spleen are not enlarged.

Laboratory findings :-

1. Peripheral blood smear shows normocytic or macrocytic (MCV increased) and normochromic red cells. The reticulocyte count is low.

2. Leucopenia: There is a marked decrease in granulocytes, though their morphology is normal.

3. Platelet count is very low (thrombocytopenia).

4. Peripheral blood smear shows no abnormal cells.

5. Bone marrow shows hypoplasia. There is a fatty degeneration of the haemopoietic tissue. The main cell types seen are lymphocytes and plasma cells.

5. Anemia in Systemic Disease:- Anemia may appear as one of the symptoms in various systemic diseases of organs other than bone marrow.

These include:-

(i)Malignant disease.

(ii) Rheumatoid arthritis, SLE and other connective tissue disorders.

(iii) Chronic renal failure.

(iv) Liver disease. (v)Alcoholism.

(vi) Hypothyroidism.

(vii) Tuberculosis.