This article explores rare red blood cell disorders, emphasising the significance of identifying uncommon causes and mechanisms of anaemia, especially in geriatric patients.

1. The myeloid series is composed of the following:

• Neutrophils
• Basophils
• Eosinophils
• Red blood cells
• Monocytes
• Macrophages
• Platelets

2. Lymphoid series is composed of lymphocytes(B or T)

In this article, I will be discussing RARE RED BLOOD CELL disorder. Let me first enumerate the known red blood cell disorders as follows:

• Anemia - Hemolytic anemia, Nutritional anemias, Hemolytic anemia
• Red cell membrane disorders
• Hemoglobinopathies
• Disorders of heme production
• Red cell enzyme deficiencies
• Polycythemia
• Hemochromatosis

Among the above disorders, we are quite familiar with anaemia, and hemoglobinopathies, I shall discuss rare red cell disorders which I have not usually come across in my routine practice as a consultant pathologist.

1. Unstable hemoglobins

1. They are autosomal dominant disorders, HbSun Prairie31 and HbBushwick32 are a few observed unstable haemoglobins. Only defective B chains have been found so far.
2. Clinically it presents when infections are treated with antioxidants drugs like sulfonamides. However, most of the cases are never suspected at this point.
3. The clinical and laboratory findings are those of hemolytic anaemia. Laboratory findings like high reticulocyte count, and isopropyl instability test can be done. Unstable haemoglobins can be identified only by DNA analysis only.[1]

2. Autoimmune hemolytic anaemia (AIHA)

1. It is usually suspected in newborns where the Coombs test is often advised. However, they are poorly suspected as age advances without any prior history of hemolytic anaemia.
2. Primary AIHA is seen when there is no known disease associated with hemolysis. Secondary AIHA is seen when hemolysis is directly associated with a disease or a drug which can cause hemolysis.
3. Diagnosis is done by the Coombs test (direct and indirect) both warm and cold antibody type. Once identified there is a good response to glucocorticoid therapy and also by avoiding any drugs which may alleviate hemolysis. [2]

3. Mechanical trauma

1. Clinician usually misses this and also the patients fail to admit thinking that has no relation to the present illness.
2. Cardiac valves mostly artificial mechanical cardiac valves are the most common cause. Sometimes habitual self-inflicting harm or repeated physical abuse may also be the causes.
3. Microangiopathic hemolytic anaemias are usually suspected and treated. The mechanism of anaemia in these situations is the shear stresses that mechanically injure red cells.
4. Schistocytes seen in peripheral smears are the evidence to diagnose anaemia due to trauma. March hematuria and running macrocytosis are some of the terms which are often used but seldom diagnosed. [3]

4. Nutritional anaemia

1. Iron, folic acid and Vit B12 are the major deficiencies in anaemia. Vitamin C is another entity which is required for iron absorption. Although required in traces deficiency of zinc, copper, manganese, molybdenum and cobalt are related to anemia.

2. Clinically epithelial manifestations are associated with zinc deficiency along with iron deficiency like angular cheilosis, glossitis, stomatitis, dysphagia, oesophagal web, hair or nail changes and easy bruising.
3. Zinc is essential during erythropoiesis. Zinc and copper are also related to each other. Excess of zinc may deplete copper. Serum levels of these trace elements can be identified after iron therapy deficiency of all these trace elements leads to a condition known as Related Iron Deficiency Anemia. [4],[5]

5. Anemia of Unknown Etiology

1. Although anaemia is related to some deficiency, all the usual laboratory reports may show normal values. Other tests, such as the level of hepcidin and erythropoietin, may guide the diagnosis and treatment of anaemia.
2. In the elderly elevated levels of pro-inflammatory cytokines may lead to elevated levels of hepcidin which decreases iron absorption from intestinal mucosa.
3. Renal dysfunction may vary erythropoietin level leading to improper stimulation of hematopoiesis.[6]

6. Idiopathic Cytopenia Of Unknown Significance (ICUS) or Clonal Cytopenia Of Unknown Significance (CCUS)

1. These anaemias result from multifactorial causes and are usually seen in the elderly. They are usually diagnoses of exclusion.
2. Somatic mutations increase with age and anemias associated with them are called clonal cytopenia of unknown significance and if no mutations are confirmed it is known as idiopathic cytopenia of unknown significance.
3. The treatment is not promising and the anemia may not respond to all the known therapies known to date. [7]

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

About the author of this article: Dr Ashok K P is a Consultant Pathologist at Trinetri Diagnostic Centre, Gadag, Karnataka.