Haematology Group C Wedyan Meshreky Helen Naguib Sharon Naguib

A 25 year old female was referred for evaluation of recently discovered anaemia. She had never been pregnant and had noted no change in menstrual flow & no intermenstrual bleeding. Her diet was normal and she took no medications. She denied any change in bowel habit or symptoms of GI/urinary blood loss. There were no abnormal physical findings. Blood film – hypochromic, microcytic cells. There was marked anisocytosis with moderate numbers of pencil and target cells. An occasional Howell-Jolly body and moderate numbers of hypersegmented neutrophils were noted.

Hb:65 g/L ( ) MCV:74 fL (80-100) WCC:4.5X 10 9 /L ( X10 9 /L) WCC differential Normal Platelets: 500 X10 9 /L ( X10 9 /L) Iron deficiency anaemia is suspected. Is the MCV result consistent with a diagnosis of iron deficiency - explain?

Microcytosis Presence of smaller than normal RBC, possessing a variable central pallor (hypochromic) Normal RBC are 7-8  m, but microcytic cells are <7  m in diameter

Normal vs Microcytic RBC

MCV MCV: average volume of a single RBC Reference interval: fL An MCV below this range indicates microcytosis

Causes Commonly caused by iron deficiency anaemia, thalassaemia and anaemia of chronic disease Rare: lead poisoning, sideroblastic anaemia and Haemoglobin E This px’s MCV=74fL therefore consistent with diagnosis of iron deficiency anaemia

Blood film: hypochromic, microcytic cells, marked anisocytosis and moderate numbers of pencil and target cells Hypochromia characterised by the presence of a central pallor in the RBC

Anisocytosis Variation in the size of RBCs, without a change in cell shape.

Anisocytosis.. Mainly associated with 2 conditions: - young RBC or polychromatophils or - smaller RBC such as microcytes It is a feature of many anaemias and other blood conditions but does not have much diagnostic value

Anisocytosis.. The red cell distribution width (RDW) is a qualitative measure of the degree of anisocytosis Useful in the differential diagnosis of microcytic anaemia. Most cases of iron deficiency anaemia have a raised RDW, whereas in thalassaemia RDW is normal Anisocytosis is often due to low Vit. B12, folic acid and iron

Blood film – There was a moderate numbers of pencil and target cells and an occasional Howell-Jolly body

PENCIL/CIGAR CELLS Morphology: Red cells shaped like a cigar or pencil Found in: Iron deficiency Anaemia

TARGET CELLS Morphology: Abnormal red blood cells (discoid shaped) resembling targets

TARGET CELLS (2) Found in: Chronic disease including - liver disease - obstructive jaundice - certain endocrinopathies - iron deficiency anaemia - post-splenectomy - thalassemia (hemoglobinopath)

HOWELL-JOLLY BODY Morphology: Round, purple staining nuclear fragments of DNA in the RBC, due to abnormal cell division.

HOWELL-JOLLY BODY Single Howell-Jolly Body: - Haemolytic anemia. - Post splenectomy, - Splenic atrophy. Multiple Howell-Jolly Bodies: - Megaloblastic anemia

Causes of Iron Deficiency Anaemia Increased iron demand (growth or pregnancy) Blood loss (peptic ulcers, hookworms, haemorrhoids, menstruation etc) Inadequate intake of Folate & B12 & Iron Iron, B12 and folate are needed for Hb synthesis and RBC production & maturation Chronic diseases,bone marrow disorders etc

Does this patient also have B 12 or Folate deficiency? Results:

Folate Body stores very little (4 weeks supply) Maintenance of folate stores is dependent on dietary intake. Absorbed in small bowel and circulates in free form or loosely bound to albumin. Essential for DNA synthesis and aa metabolism.

Folate Deficiency May be due to: Dietary folate deficiency Coeliac disease Alcoholism Pregnancy Hypothyroidism Drugs (eg. Phenytoin, trimethoprim) Liver disease

Vitamin B 12 In contrast to folate, the body stores large amounts (2-6yrs supply) Anaemia due to B12 deficiency takes ~2yrs to develop due to large stores in liver Deficiency of B12 or folate impairs Thymidine Synthase function, hence interupts DNA synthesis   megaloblastic anaemia

Serum Ferritin Most specific biochemical test that correlates with total iron stores in the body Low levels ( <15ug/L) reflect depleted iron stores.

Data is typical of Iron deficiency Anaemia Microcytic (MCV < 80fL) Low Hb (65g/L) Raised Platelets (500x10*9/L) Low Serum Ferritin (5ug/L) Hypochromic cells on blood film Folate deficiency (2nmol/L)

Treatment Establish cause of anaemia and treat underlying cause. Iron supplementation. Increase dietary intake of Iron, Folate & B12.