Anemia: A Red Blood Cell Disorder

Anemia is a clinical condition in which total number of red blood cells or the quantity of hemoglobin in blood declines than the normal level so the oxygen binding ability of hemoglobin is decreased. The word anemia is taken from a Greek word meaning lack of blood as hemoglobin deficiency prevails in the blood. Hemoglobin present inside the red blood cells normally carries oxygen from lungs to the tissues and anemia causes hypoxia in organs. As all human cells are dependent upon oxygen for survival, anemia can lead to a wide variety of symptoms depending upon degree of destruction caused. Anemia is the most common disorder of blood and different types of anemia are known depending upon the underlying causes. Anemia can be classified in a variety of ways for example, on the basis of morphology of the RBCs, underlying etiologic mechanisms and discernible clinical spectra.

There are three main classes of anemia for example, hemorrhage characterized by excessive blood loss followed by hemolysis where excessive destruction of the blood cells take place and ineffective hematopoiesis identified by deficient production of red blood cells. There are two major approaches for anemia. The first one is kinetic approach which involves evaluation and production, destruction and loss of the red blood cells. The second approach is the morphologic approach which involves characterization of anemia on the basis of size of red blood cells. The morphologic approach involves use of easily available and low cost laboratory tests to identify anemia. The normal level of hemoglobin is typically different in males and females. Males suffer from anemia when the total hemoglobin levels become less than 13.5 gram/100ml while for females it must be less than 12.0 gram/100ml.


Anemia can be classified into following types:

1. Production versus destruction or loss
The kinetic approach gives the most relevant classification of anemia. This approach focuses on the evaluation of several hematological parameters for example, the blood reticulocyte count. This then classifies the defects concerned with decreased RBC production as well as its increased destruction and loss. Clinical signs of destruction of RBCs show hemolysis in the blood smear. Increased level of LDH suggests increased loss of blood cells.

2. Red blood cell size
The morphological approach classifies anemia on the basis of size of RBCs. This can be done either automatically or by analyzing the peripheral blood smear. The size of red blood cells is reflected in terms of mean corpuscular volume (MCV). If the size of cell is less than 80 fl then anemia is said to be microcytic and if it is 80-100 fl then anemia is normocytic. If the size of cell is more than 100 fl then anemia is classified as macrocytic. This approach quickly gives some idea about the cause of anemia for example microcytic anemia is the result of iron deficiency. The peripheral blood smear often gives an idea about the white blood cells. Abnormal picture of white blood cells projects towards a defect in the bone marrow.

a. Microcytic anemia
Microcytic anemia is primarily the result of failure of synthesis or insufficient production of hemoglobin in blood and a number of etiologies are also responsible for it. Iron deficiency anemia is the most common type of anemia which may arise due a number of factors. In this type of clinical condition RBCs appear hypochromic and microcytic when viewed under microscope. Iron deficiency anemia is caused due to insufficient intake or absorption of iron in the body. Iron is very important for hemoglobin production and any insufficiency may result in decreased incorporation of hemoglobin in the red blood cells. In United States about 20% females of childbearing age suffer from iron deficiency anemia while only 2% of males of same age group suffer from this clinical condition.

The prime cause of this form of anemia in the premenopausal women is excessive blood loss during menstrual cycle. Studies have shown that iron deficiency without anemia results in poor performance as well as low IQ in girls, although some socioeconomic factors may also be marked responsible for it. Iron deficiency sometimes also causes abnormal fissuring of angular sections of the lips. Iron deficiency anemia can also result from the bleeding of lesions of gastrointestinal tract. Fecal blood testing, occult blood testing, upper endoscopy and lower endoscopy can help in detection of bleeding of the gastrointestinal tract. In men and post-menopausal women the bleeding may be due to colorectal cancer. Parasitic infestations of parasites namely, Amoeba, hookworm, Schistosoma and whipworm is most common cause of iron deficiency anemia.

b. Macrocytic anemia
Macrocytic anemia can be further divided into megaloblastic and non-megaloblastic macrocytic anemias. The major cause of megaloblastic anemia is failure of DNA synthesis however, RNA synthesis occurs normally and this results in restricted cell division of the progenitor cells. This form of anemia can also be found associated with the neutrophil hypersegmentation. The non-megaloblastic anemia is most commonly found associated with alcoholism. Vitamin B12 deficiency is the most common feature of this type of anemia and the symptoms include peripheral neuropathy and subacute combined degeneration of the cord resulting in balance difficulties of the spinal cord. Other features comprise red and smooth tongue and glossitis. The treatment of the vitamin B12 deficiency anemia was first given by William Murphy. He allowed the dogs to bleed till they became anemic and then fed them a variety of substances in order to cure anemia. He concluded that ingestion of large amounts of liver resulted in diminished symptoms of anemia. George Minot and George Whipple then isolated vitamin B12 from liver and all these three scientists shared the Noble Prize in medicine in 1934.

c. Normocytic
This type of anemia occurs when the overall levels of hemoglobin keep on increasing but the size of red blood cells remain normal. This can be caused by acute blood loss, anemia due to chronic disease, hemolytic anemia and aplastic anemia.

d. Dimorphic anemia
When two or more factors causing anemia act simultaneously at a time then this form of clinical condition comes into play.

e. Heinz body anemia
Heinz bodies are formed in the cytoplasm of RBCs and appear like small dots when viewed under microscope. A number of factors are believed to be responsible for this clinical condition and some drugs may also participate in this form of anemia. It can be triggered in cats and dogs by feeding them on onions and zinc.

f. Hyperanemia
It is a very severe form of anemia characterized by lowered concentration of hematocrit about less than 10%.

g. Refractory anemia
This form of anemia fails to respond against any treatment. It is secondarily associated with the myelodysplastic syndromes. Iron deficiency anemia can also be placed under this category.


Anemia can be classified as a clinical condition with impaired red blood cell production, increased RBC destruction, blood loss and fluid overload. A number of factors act simultaneously to cause anemia. Blood loss is the most frequent symptom of anemia followed by iron deficiency. Anemia of impaired production can occur due to disturbance of proliferation and differentiation of stem cells. This symptom can cause pure red cell aplasia followed by aplastic anemia which affects all types of blood cells. Insufficient production of erythropoietin causes renal failure and anemia of endocrine disorders can also crop up. Disturbance of proliferation and maturation of erythroblasts is responsible for the appearance of pernicious anemia which is a form of megaloblastic anemia caused by vitamin B12 deficiency resulting in impaired vitamin B12 absorption. This form of megaloblastic anemia also causes anemia of folic acid deficiency.

The levels of hematocrit also decline so erythropoietin response also diminishes resulting in anemia of prematurity. It generally occurs in the infants of 2-6 weeks of age. Iron deficiency anemia also causes deficient heme synthesis. Thalassemias cause deficient globin synthesis. Myelophthisic anemia is a very severe form of anemia where bone marrow is replaced by other materials like granulomas or malignant tumors. Anemias of increased red blood destruction are generally classified as hemolytic anemias and are characterized by jaundice and increased levels of low density lipoproteins. Trauma and surgery also cause blood loss and even the gastrointestinal tract lesions also result in chronic blood loss. Fluid overload causes decreased hemoglobin concentration and apparent anemia
Signs and symptoms

Anemia in some individuals may remain hidden as the symptoms do not arise very frequently. The signs and symptoms may depend upon the underlying cause. Individuals suffering from anemia generally show non-specific symptoms like weakness, general malaise and poor concentration. They may also report shortness of breath on exertion. In very severe forms the body compensates for the lack of oxygen carrying capacity of blood cells by increasing the cardiac output. The patient may also complain of palpitation, angina, and intermittent claudication of legs and signs of heart failure. Other prominent symptoms include jaundice, bone deformities or leg ulcers. In severe forms tachycardia, bounding pulse, flow murmurs and cardiac ventricular hypertrophy may also occur. Symptoms of heart failure may also arise. Pica, a symptom of iron deficiency arises after the consumption of non-food items like paper, wax, glass and ice. Chronic anemia may also cause behavioral changes in the children resulting in impaired neurological development. Restless legs syndrome is very common in individuals with iron deficiency anemia. Less frequent symptoms include swelling of legs, arms, chronic heartburn, vomiting, increased sweating and loss of blood in stool.


A complete blood count is typically used for the diagnosis of anemia. Apart from determining the number of red blood cells and hemoglobin levels automatic counters also measure the size of red blood cells by using flow cytometry which gives a clear picture of anemia. Examination of a stained blood smear under microscope also gives a clear cut idea about this disease. Reticulocyte count and kinetic approach are very commonly used in diagnosis. A recticulocyte count is actually a quantitative measure of bone marrow's production of new red blood cells. If automated blood count is not available then reticulocyte count can be taken into consideration for disease diagnosis.


Treatments mainly focus on type and cause of anemia. Iron deficiency anemia arising due to nutritional uptake is generally rare in men and post-menopausal women. Mild to moderate iron deficiency anemia is treated by oral iron supplementation of ferrous sulfate, ferrous fumarate or ferrous gluconate. While taking iron supplements an individual may experience upset stomach as well as darkened feces. Vitamin C increases body's ability to absorb iron so taking orange juice along with iron supplements may be of great help. Vitamin supplements taken orally or intramuscularly can help in replacing some of the specific deficiencies. Chronic anemia can be treated with chemotherapy and the medical experts also advise use of recombinant erythropoietin to stimulate red blood cell production. In very severe cases blood transfusion becomes necessary. Anemia may be genetic. Hereditary disorders shorten the life span of red blood cells and thus, cause anemia. Hereditary disorders can also impair hemoglobin production and cause this disease. Depending upon the degree of genetic abnormality anemias may be mild, moderate and severe.

Navodita Maurice