Anemia Introduction Dr. Sachin Kale, MD. Asso. Prof, Dept. of pathology In charge, Central Laboratory, MGM.

Outline Introduction to anemias Introduction to hematology and hematopoiesis Introduction to anemias Iron deficiency anemias Megaloblastic anemia. Sickle cell anemia

Anemias Signifies a decrease in Hb or Hct and represents underlying disease than a specific diagnosis Accepted definitions - Male: < 13.5 g/dl Female: < 12.5 g/dl Pregnancy & Children - ( 6 m – 8 yrs): < 11 g/dl Preterm infants: < 14 ; Full term infant: < 13.5

Anemias SaO2 ( % of heme groups occupied by O2) and PaO2 ( amount of O2 dissolved in plasma) are normal; since O2 exchange in lungs are normal. However oxygen content (total amt of O2 available) is decreased owing to reduction in Hb concentraion.

Mature RBC Anucleate cells Devoid of mitochrondria – lack citric acid cycle, beta oxidation of fatty acid, oxidative phosphorylation Metabolize glucose by anerobic glycosylation – lactate is the end product. Generate glutathione via pentose phosphate shunt.

Mature RBC Reduce heme iron from ferric (+3) to ferrous (+2) state using methemoglobin reductase system Synthesizes 2,3 bisphosphoglycerate via Rappapor-Luebering shunt. ( used for right shifts in O-D curve) ABO & Rh antigens on membranes.

Mature RBC Senescent RBCs are removed mainly by extravascular hemolysis – endproduct is lipid soluble unconjugated bilirubin. Lesser extent – intravascular hemolysis.

Anemia: symptoms Tissue hypoxia Dyspena with exertion Weakness, fatigue, anorexia, insominia, inability to concentrate, and dizziness (CNS hypoxia)

Basic pathophysiological categories of anaemia Blood loss Impaired red cell production Inadequate supply of nutrients essential for eythropoiesis, such as: . iron deficiency vitamin B 12 deficiency folic acid deficiency protein-calorie malnutrition other less common deficiencies

Impaired red cell production Depression of erythropoietic activity Anaemia associated with chronic disorders. such as: infection connective tissue disorders inflammatory disorders disseminated malignancy Anaemia associated with renal failure Aplastic anaemia Anaemia due to inherited disorders, such as thalassaemia

Impaired red cell production Anaemia due to replacement of normal bone marrow by: Leukaemia Lymphoma myeloproliferative disorders Myeloma myelodysplastic disorders

Excessive red cell destruction Due to intrinsic defects in red cells Due to extrinsic effects on red cells

General evidence of hemolysis Evidence of increased HB breakdown: Jaundice and Hyperbilirubinemia Evidence of compensatory erythroid hyperplasia: Reticulocytosis Evidence of damage to red cells: Spherocytosis Fragmentation RBCs Heinz bodies

Classification of anemias Microcytic anemias: ( MCV < 80 fl) Iron deficiency (most common) Thalassemia Anemia of chronic disease Sideroblastic anemia

Classification of anemias Macrocytic anemia (MCV > 100 fl) B12 deficiency Folate deficiency Alcoholic liver disease Hypothyroidism

Normocytic anemia ( MCV 80 – 100 fl) Reti count: (< 2%) Acute blood loss Early iron deficiency Aplastic anemia Anemia of chronic disease Renal disease

Normocytic anemia ( MCV 80 – 100 fl) Reti count: (> 3%) ( Intrinsic RBC defect) Membrane defects Congenital spherocytosis/elliptocytosis Paroxysmal Nocturnal Hemoglobinuria (PNH) Abnormal hemoglobins: Sickle cell disease variants Enzyme deficiencies G6PD & Pyruvate kinase deficiency.

Normocytic anemia ( MCV 80 – 100 fl) Reti count: (> 3%) ( Extrinsic RBC defect) Autoimmune hemolytic anemias ( warm and cold) Paroxysmal cold hemoglobinuria Microangiopathic hemolytic anemia

Work up of anemic patient

Chipmunk facies

RBCs in health and disease

Understanding CBC: the complete blood count Haematocrit is 3 times the HB value: Rule of 3. RBC count usually parallels HB and Hct, In thallasemias RBC count is normal to increased even though Hb is low. RDW: Red cell distribution width WBC count: Total and differential Blood film:

RBC indices MCV: volume of average red cell (fl or um3) MCV = Hctx1000/RBC count ( in millions per ul) MCH: content (wt) of Hb of average red cell MCH = Hb (g/l)/RBC ( in millions per ul) MCHC: average concentration of Hb in given volume of packed cells. MCHC: Hb(g/dl)/Hct

X’s Edition

Question 1

All of the following cause microcytic anemia except Iron deficiency anemia Thalasemia Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Alcoholic liver disease Anemia of chronic disease

All of the following cause microcytic anemia except Iron deficiency anemia Thalasemia Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Alcoholic liver disease Anemia of chronic disease

Question 2

Hereditary spherocytosis All of the following cause normocytic anemia with reti count < 2%, except Aplastic anemia Hereditary spherocytosis Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Acute blood loss Anemia of renal disease

Hereditary spherocytosis All of the following cause normocytic anemia with reti count < 2%, except Aplastic anemia Hereditary spherocytosis Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Acute blood loss Anemia of renal disease

Question 3

Which of the following is True MCV = Hctx1000/RBC count MCH = Hb (g/l)/RBC Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor MCHC: Hb(g/dl)/Hct All of the above

Which of the following is True MCV = Hctx1000/RBC count MCH = Hb (g/l)/RBC Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor MCHC: Hb(g/dl)/Hct All of the above

Question 4

Check up. CBC = Low MCV, Low Hb, WBCs: N 26 yr, female, routine Check up. CBC = Low MCV, Low Hb, WBCs: N

You expect further studies to reveal Positive Sickle screen Increased HbA2 & F Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Normocytic ane. Increased reti Low Sr. Ferritin

You expect further studies to reveal Positive Sickle screen Increased HbA2 & F Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Normocytic ane. Increased reti Low Sr. Ferritin

Question 5

Which of the following is present in both IDA & Thalassemia Low Ferritin concentration Microcytic RBC Indices Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Abnormal Hb electrophoresis All of the above

Which of the following is present in both IDA & Thalassemia Low Ferritin concentration Microcytic RBC Indices Germ cell tumors Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Abnormal Hb electrophoresis All of the above

A well executed CBC followed by its proper interpretation has its worth in gold and a shrewd clinician make use of this simple and cheap test for diagnosing hematological and even non-hematological disorders.. Dr. M. B Agrawal.

“ Mind is like a Parachute - it works only when it is open “ “Eyes can only see, what mind can think! “ 54

Thank you!