Dr. YK Amdekar writes on pallor and its significance as a common physical finding that can aid in the diagnosis of anaemia.

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Before you begin, take this quick quiz to test your knowledge.

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What is pallor?

Pallor refers to a subjective feeling of paleness or whitish hue instead of pinkish hue to the skin. It is not the equivalent of anaemia. It most commonly occurs due to reduced haemoglobin- anaemia but, may also be caused by peripheral vasoconstriction as what happens in rising fever or due to sudden stress or shock. At times, stretched skin due to severe oedema also looks pale to simulate anaemia and is referred to as waxy pallor.

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What is anaemia?

Anaemia refers to decreased red blood cell mass lower than age-appropriate standard norms that is accompanied with reduced haemoglobin. It results in decreased oxygen carrying capacity. It is important to note that haemoglobin in normal newborn is as high as 16-17 Gm%. At 3 months of age, it comes down to as low as 10 Gm% and then slowly rises to adult level over the next few years. So, 10 Gm% haemoglobin in newborn is anaemia and at 3 months it is normal because it is a physiological dip as a result of decreased erythropoiesis due to increased tissue oxygenation and reduced production of erythropoietin.

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How to make sure that pallor is due to anaemia

It is easy to note that paleness due to rising fever or shock is restricted only to the periphery and also, the skin seems cold in a sick-looking child. Severe oedema is obvious cannot be missed.

Besides the skin looking pale, mucous membranes are also pale due to anaemia. However, conjunctiva may not appear pale despite anaemia in case of conjunctivitis. Also, the mucous membrane in the mouth does not look pale due to glossitis. Hence, it is important to look for anaemia in multiple sites for correct interpretation.

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Is it possible to assess severity of anaemia on clinical examination?

It is difficult to assess the degree of anaemia in a dark-skinned individual. However creases on the palm may offer some clue. Normally creases are well seen in normal individuals while they are not very visible in an anaemic person as they also become pale. It is best to compare your own palm with that of the patient to get a fair idea of anaemia and also to some extent the degree of anemia, though one must note that such a clinical sign is not very sensitive and not a substitute to haemoglobin estimation.

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Physiology of anaemia

It is important to know basic physiology that would help in diagnosing the type of anaemia. Stem cells in the bone marrow go through several maturation phases (progenitor cell to erythroblast to normoblast to reticulocyte to mature RBC). Haemoglobin is incorporated in the late stages of normoblast and continues to be present in reticulocytes and RBCs.

The life of a reticulocyte in peripheral circulation is just one day while the life of an RBC is about 120 days. Naturally, there are many RBCs in peripheral blood smear but very few reticulocytes. Routinely, there are no normoblasts in peripheral circulation. When RBCs are lysed at the end of their life, haemoglobin is released, globin a protein is stored in the body and heme is broken down to iron and biliverdin. Iron is also stored and biliverdin forms bilirubin that needs to be conjugated by liver enzyme to make it water-soluble and excreted via urine and stool.

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Clinical relevance of physiology of anaemia

It is obvious from physiology that increased haemolysis of RBCs will produce lots of unconjugated bilirubin that cannot be handled by the liver and so result in jaundice. It is haemolytic jaundice in spite of the liver being normal but not being able to handle excessive load of lysed RBCs. This being unconjugated bilirubin is not water-soluble and so can’t be excreted in urine. Thus urine is not dark-coloured in haemolytic anemia.

Increased number of reticulocytes or presence of normoblasts in peripheral blood smear suggests increased bone marrow production to compensate for increased RBCs destruction as what happens in haemolytic anaemia. Thus jaundice is not necessarily a liver disease.

On the other hand, if there are small number of RBCs along with decreased number of WBCs and platelets, it would suggest bone marrow suppression as what happens in aplastic anaemia. Presence of blast cells in peripheral blood smear would suggest leukaemia.

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Types of haemoglobin

There are three types of haemoglobin-

• HbA (98 to 99% of total haemoglobin in adults) seen in normal individuals beyond the age of 2 to 4 months, consisting of alpha and beta chains
• HbA2 consisting of alpha and delta chains that is also present in normal individuals beyond 2 to 4 months but is in small amount- just 1 to 2% of total haemoglobin
• HbF (foetal haemoglobin) found up to 2 to 4 months of age, consisting of alpha and gamma chains, and disappears thereafter in normal individuals

Persistence of foetal hemoglobin beyond 4 months of age or increased amount of HbA2 (beyond 2% of total haemoglobin) suggests abnormality.

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Nutrients necessary to form haemoglobin

Iron, vitamin B12, and folate are major nutrients required to form haemoglobin, deficiency of which leads to significant anaemia. Less than 10% iron in food is absorbed through intestines in iron-sufficient individuals as the process of absorption is hindered by the presence of calcium and phytates in the diet. However, nature maintains balance by increasing iron absorption in iron-deficient individuals. Heme iron (from non-vegetarian food) is better absorbed than non-heme iron. Vegetarian food lacks in vitamin B12 unless the person consumes an adequate amount of dairy products. It is absorbed in the ileum and not jejuum (most other nutrients are absorbed through the jejunum). Other factors that contribute to a smaller extent, include vitamin C, few micronutrients and thyroxin, deficiency of which cause mild degree of anaemia.

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Types of anemia and their clinical correlates

Deficiency anemia: It is the most common type of anaemia and is mainly caused due to a diet deficient in iron, B12 or folate. At times it may also be a result of deficient digestion and/or absorption despite adequate intake as is the case in intestinal diseases. It may also be due to loss of blood as what happens in hookworm infestation or intestinal bleeding. Thus, mere supplementation may not suffice in case of intestinal pathological conditions. Such patients present with refractory anaemia. Iron deficiency anaemia presents with platenychia or koilonychia while B12 deficiency has knuckle pigmentation. There is no hepatosplenomegaly and the patient does not look so sick.

Bone marrow disorders: They result either from marrow suppression as in aplastic anaemia or due to infiltration of marrow as in leukaemia or other similar disorders. Such patients present with purpuric spots or other bleeding manifestations and are sick looking. Infiltrative marrow disorders present with hepatosplenomegaly while aplasia has no organomegaly.

Haemolytic anaemia: It is either due to congenital abnormality as in thalassemia, other haemoglobinopathies or spherocytosis while it be acquired due to antibody-mediated destruction as in autoimmune haemolytic anaemia. Such patients present with mild jaundice besides severe anaemia and have hepatosplenomegaly. Those with congenital disorder are not sick-looking, but short with abnormal facial characteristics due to extramedullary erythropoiesis necessary to compensate excessive haemolysis.

The following table summarises the above findings:

	Liver	Spleen	Jaundice	Sick	Others
Iron deficiency	-	-	-	no	nail signs
B12 deficiency	-	-	-	no	knuckle sign
Congenital hemolytic	++	++	+	no	facial signs
Aquired hemolytic	++	++	+	mild	-
Aplastic	-	-	-	sick	-
Leukemia	++	++	-	sick	purpura

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Blood- Basic investigations

	WBC	Platelets	MCV	RDW	Others
Iron deficiency	N	N	low	high	micro-hypo
B12 deficiency	low	low	high	high	micro
Hemolytic	N	N	variable	N	micro-hypo
Bone marrow	low	low	variable	variable	blasts

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Treatment

Deficiency anaemia needs relevant supplementation. Oral iron therapy works well as iron absorption is enhanced in the deficient state. Parenteral therapy is not indicated and packed cell blood transfusion is not necessary unless the child presents with cardiac failure that is rare. B12 deficiency often needs parenteral therapy as absorption depends on intrinsic gastric factor. However, oral treatment must be tried first. Folate deficiency is treated with oral supplements. Diet modification is important to prevent recurrence. Other types of anaemia need specialised care and should be left to specialists.

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Practice pearls

1. Pallor is not equivalent of anaemia. Subjective assessment in mild or moderate anaemia is not dependable, especially in dark-skinned individuals.
2. Creases on palms offer clues to severity of anaemia to some extent.
3. A simple algorithm (depicted above) helps in clinical diagnosis of the type of anaemia.
4. CBC and peripheral blood smear almost confirms the type of anemia, but may need further specilised tests to fine-tune the diagnosis.
5. Oral supplementation in deficiency anaemia is adequate and in case of refractory deficiency anaemia, one must rule out intestinal disorders.
6. Specialised care is necessary for other types of anaemia.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.