This document provides an overview of an approach to evaluating and classifying a case of anemia. It discusses hematopoiesis and red blood cell production regulated by erythropoietin. For a patient presenting with anemia, the evaluation includes a complete blood count, peripheral smear to examine red blood cell morphology, reticulocyte count, and tests of iron status. Based on history and examination, further testing may include bone marrow examination. Anemias are classified as hypoproliferative due to marrow defects, ineffective erythropoiesis, or decreased red blood cell survival from blood loss or hemolysis based on reticulocyte response and red blood cell findings.

1. Approach to a case of
Anemia
- Dr Rahul Arya
- Assistant Professor
- Department of Medicine

2.  Hematopoiesis is the process by which the formed elements of blood are
produced.
 The process is regulated through a series of steps beginning with the
hematopoietic stem cell.
 Stem cells are capable of producing red cells, all classes of granulocytes,
monocytes, platelets, and the cells of the immune system.
 For red cell production, erythropoietin (EPO) is the primary regulatory hormone.
 EPO is required for the maintenance of committed erythroid progenitor cells that,
in the absence of the hormone, undergo programmed cell death (apoptosis).

3.  In the bone marrow, the first morphologically recognizable erythroid precursor is
the pronormoblast.
 This cell can undergo four to five cell divisions, which result in the production of
16–32 mature red cells.

4. Anemia
WHO Definition:-
Anemia is a condition in which the number of red blood cells
(and consequently their oxygen-carrying capacity) is insufficient
to meet the body’s physiologic needs which vary by age, sex,
altitude, smoking and pregnancy status.

5.  Anemia is a state in which the level of hemoglobin in the
blood is below the normal range appropriate for age and sex
(pregnancy and altitude also should be taken into account).
 The likelihood and severity of anemia are defined based on
the deviation of the patient’s hemoglobin or hematocrit, from
values expected for age and sex matched normal subjects.

6. Clinical Presentation
Sign and Symptoms:-
 Acute Anemia:-
 It is due to blood loss or hemolysis.
 10-15% loss  signs of vascular instability
 > 30% loss  Postural hypotension and Tachycardia
 > 40% loss  signs of hypovolemic shock including confusion,
dyspnea, diaphoresis, tachycardia, hypotension.
 Acute hemolysis- acute back pain, free hemoglobin in the plasma
and urine, and renal failure.

7.  Chronic Anemia:-
 Weakness, Fatigue, Lassitude
 Light headedness, Giddiness, fainting/ syncope
 Anorexia
 Palpitation
 Breathlessness
 Tinnitus
 Lack of concentration
 Tingling sensation in extremities
 Menstrual irregularities

8. APPROACH TO THE PATIENT
 The evaluation of the patient with anemia requires a careful
history and physical examination.

9. History
 Nutritional history related to drugs or alcohol intake and
family history of anemia should always be assessed.
 Geographic backgrounds and ethnic origins.
 Exposure to certain toxic agents or drugs.
 Systemic symptoms like fever, weight loss, night sweats.

10. Physical Examination
 Pallor is present
 Pallor is seen in palpebral conjunctiva.

11.  Also seen at mucous membrane, nail beds and palmar
creases.
 If the palmar creases are lighter in color than the surrounding
skin when the hand is hyperextended, the hemoglobin level is
usually < 8 g/dL.

12.  Icterus- ?hemolytic anemia
 Lymphadenopathy- lymphoproliferative disease
 Pedal edema
 Koilonychia- IDA
 Forceful heartbeat
 Strong peripheral pulses
 Systolic “flow” murmur.
 Splenomegaly
 Hepatomegaly

13. LABORATORY EVALUATION
 Complete blood count (CBC):-
 It includes the hemoglobin, hematocrit, and red cell indices.
 Red cell indices:
o mean cell volume (MCV) in femtoliters,
o mean cell hemoglobin (MCH) in picograms per cell
o mean concentration of hemoglobin per volume of red cells
(MCHC) in grams per deciliter.

14. Normal hemoglobin values

16. Hematocrit
 The hematocrit is the proportion, by volume, of the blood
that consists of red blood cells.
 The hematocrit is expressed as a percentage.
 The percentage by volume of packed red blood cells in a
given sample of blood after centrifugation.
 Normal values-
 Adult male- 47 ± 7
 Adult female- 42 ± 5

18. RBC Indices
mean corpuscular volume (MCV)
mean corpuscular hemoglobin (MCH)
mean corpuscular hemoglobin concentration
(MCHC)
red cell distribution width (RDW).

19. Mean corpuscular volume (MCV)
(Size)
 It measures the average volume of a red blood cell by
dividing the hematocrit by the RBC count
 MCV = (hematocrit × 10) / red cell count
 Normal value  90 ± 8 fL
 Normocytic anemias  normal size
 Microcytic anemias (< 80 fL) small size
 Macrocytic anemias (>100 fL)  large size

21. Mean corpuscular hemoglobin
(MCH)
The average weight of hemoglobin in an RBC.
MCH = (hemoglobin × 10 )/ red cell count.
Normal value = 30 ± 3 pg.

22. Mean corpuscular hemoglobin concentration
(MCHC)
( Color)
 The MCHC measures the average concentration of
hemoglobin in a red blood cell.
 MCHC = (hemoglobin × 10 )/ hematocrit or MCH/MCV.
 The MCHC categorizes red blood cells according to their
concentration of hemoglobin.
 Normochromic
 hypochromic.
 There is no hyperchromic category.

23. Red blood cell distribution width
(RDW)
 RDW is a measure of the variation of RBC size
 Higher RDW values indicate greater variation in size.

24. Peripheral Blood Smear
 Anisocytosis :- RBCs of unequal size.
- The degree of anisocytosis usually correlates with
increases in the RDW
 Poikilocytosis :- RBCs of unequal shape.
- Poikilocytosis suggests a defect in the maturation of red cell
precursors in the bone marrow or fragmentation of circulating
red cells.

26. Microcytic hypochromic Macrocytic normochromic

27.  Polychromasia—red cells that are slightly larger than normal
and grayish blue in color on the Wright-Giemsa stain.
 These cells are reticulocytes that have been prematurely
released from the bone marrow, and their color represents
residual amounts of ribosomal RNA.

28. Reticulocyte Count
 Reticulocytes are red cells that have been recently released
from the bone marrow.
 They are identified by staining with a supravital dye that
precipitates the ribosomal RNA.
 These precipitates appear as blue or black punctate spots
and can be counted manually.
 Normally, the reticulocyte count is 1%.

29.  Elevation of the reticulocyte count above 1% (reticulocytosis)
is a sign of rapid red blood cell production.
 In the face of established anemia, a reticulocyte response less
than two to three times normal indicates an inadequate
marrow response.

30.  Reticulocyte (%) = [Number of Reticulocytes / Number of
Red Blood Cells] X 100.
 Corrected reticulocyte count
= reticulocyte % ×(patient’s hemoglobin/
expected hemoglobin)
Or
=reticulocyte % ×(patient’s hematocrit/
expected hematocrit)

31.  Reticulocyte production index  calculated if
polychromatophilic macrocytes are present.
 This is done to correct for longer Life of prematurely released
reticulocytes in the Blood.
 The reticulocyte count, already corrected for anemia, should
be divided again by 2.

32. Tests of Iron Supply and Storage

33. Bone Marrow Examination

34. Bone Marrow Examination
 Bone marrow aspiration and biopsy.
 It is indicated in patients with hypoproliferative anemia and
normal iron status.
 Marrow examination can diagnose primary marrow disorders
such as myelofibrosis, a red cell maturation defect, or an
infiltrative disease.
 myeloid/erythroid [M/E] ratio.
 Marrow smear or biopsy can be stained for the presence of
iron stores.

35. Classification of anemia

36. The functional classification of anemia has three
major categories.
1) Marrow production defects (hypoproliferation)
2)Red cell maturation defects (ineffective
erythropoiesis) and
3)Decreased red cell survival (blood loss/hemolysis).

37.  A hypoproliferative anemia is typically seen with a low reticulocyte
production index together with little or no change in red cell morphology
(a normocytic, normochromic anemia).
 Maturation disorders typically have a slight to moderately elevated
reticulocyte production index that is accompanied by either macrocytic
or microcytic anemia.
 Increased red blood cell destruction secondary to hemolysis results in an
increase in the reticulocyte production index to at least three times
normal.

39. Thank You