13 August 2017

Lecture #12b: Enumeration of Blood Cells


EOSINOPHIL COUNT                                                                                                                     

The procedure for eosinophil count consists of diluting the blood with an eosinophil diluting fluid, charging a counting chamber, counting the eosinophils through the microscope, and making the calculation.

Equipment

1.     White cell pipette
2.     Eosinophil diluting fluid
3.     Cotton balls and alcohol
4.     Sucking tube
5.     Puncturing device
6.     Microscope
7.     Counting chamber which maybe any of the following:
a.     Improved Neubauer ruling counting chamber
b.     Fuchs–Rosenthal counting chamber
c.     Speirs–Levy counting chamber

Eosinophil diluting fluid

1. Phloxine diluting fluid

Propylene glycol – 50 ml
Distilled water – 40 ml
1% aqueous solution of phloxine – 10 ml
10% aqueous solution of sodium carbonate – 1 ml

2. Pilot’s solution

This has the same composition as phloxine diluting fluid except that 100 units of heparin should be added. Heparin keeps the cells clumping. Sodium carbonate lyses all white cells except eosinophils. Phloxine stains the eosinophils red. Propylene glycol renders the red cells invisible

3. Dunger’s diluting fluid

2% aq. Eosin – 5 cc
Acetone – 5 cc
Distilled water – 90 cc

4. Manner’s diluting fluid

Urea – 50 g
Distilled water – 100 ml
Trisodium citrate – 0.5 g
Phloxine – 0.1 g

5. Randolph’s diluting fluid

Phloxine – 0.1 g
1% calcium chloride – 100 ml
Propylene glycol – 100 ml

6.     Tannen’s diluting fluid

Neutral red iodide solution (0.2%) – 100 ml
0.1  N NaOH – 2.1 ml

7. Hinklemann’s fluid

Eosin yellow – 0.5 g
Formaldehyde – 0.5 g
95% phenol – 0.5 ml

Any of the following three types of counting chamber may be used

1. Improved Neubauer Ruling Counting Chamber

It has 2 ruled section; each section has an area of 9 sq.mm and a depth of 0.1mm. Therefore, the volume of 1 section is 9 x 0.1 = 0.9 cu.mm. and the volume of 2 sections is 2 x 0.9 = 1.8 cu.mm.

2. Fuchs–Rosenthal Counting Chamber

This counting chamber has 2 ruled sections; each has an area of 16 sq.mm. (has 16 big squares). Each is further subdivided into 16 medium squares. It has a depth of 0.2mm. Therefore, the volume of 1 section is 16 x 0.2 = 3.2 cu.mm. and the volume of 2 sections is 2 x 3.2 = 6.4 cu.mm.





3. Speirs–Levy Counting Chamber

This chamber has 4 sections. Each section has an area of 10 sq.mm. and a depth of 0.2 mm. each sq.mm. is further subdivided into 16 medium squares. Therefore, the volume of 1 section is 10 x 0.2 = 2 cu.mm. and the volume of the four section is 4 x 2 = 8 cu.mm.




Methods of eosinophil count:

1. Randolph’s method

Counting chamber used – Improved Neubauer
No. of squares counted – 9 big squares
Area in sq mm – 9 sq.mm.
Depth of chamber – 0.1 mm
Volume where actual count is done – 0.9 cu.mm.
Area correction factor – 1/9
Depth correction factor – 10
Volume correction factor – 1/0.9
Ratio of dilution – 1: 10
Dilution correction factor – 10

Computation:

E in big squares                      x          10        =          E/cu.mm
        0.9

E/cu.mm         x          0.001   =                       x 109/liter

2. Thorn’s method

Counting chamber used – Fuchs – Rosenthal chamber
No. of squares counted – 16 big squares
Area in sq.mm – 16 sq.mm
Depth of chamber – 0.2 mm
Volume where actual count is done – 3.2 cu.mm
Area correction factor – 1/16
Depth correction factor – 10/2 or 5
Volume correction factor – 1/3.2
Ratio of dilution – 1:10
Dilution factor – 10

Computation

E in 16 big squares     x          10        =          E/cu.mm or ul
           3.2

E/cu.mm         x          0.001   =                        x 109/liter

3. Speir’s method          

Counting chamber – Speirs – Levy chamber
No of squares counted – 4 sections of 10 squares ( 40 squares in all)
Area in sq.mm – 40 sq.mm
Depth of chamber – 0.2 mm
Volume where actual count is done – 8 cu.mm
Area correction factor – 1/40
Depth correction factor – 5
Volume correction factor – 1/8
Ratio of dilution – 1:10
Dilution factor – 10

Formula

E in 40 big squares     x          10        =          E/cu.mm or ul
           3.2

E/cu.mm         x          0.001   =                        x 109/liter

4. Friedman’s method

Technique and method of calculation are the same as Randolph’s method. It uses a diluting fluid which stains the eosinophils only and the unstained leukocytes stay as gray bodies.

5. Pilot’s method

Counting chamber – Improved Neubauer
No. of squares used – 4 sections of 9 squares each
Area in sq.mm. – 16 big squares
Area correction factor – 1/16
Depth factor – 1:10
Volume factor – 3.6

E in 36 big squares     x          10        =          E/cu.mm or ul
           3.2

E/cu.mm         x          0.001   =                        x 109/liter

Formula to obtain the % value of eosinophils

            Eosinophils / cu.mm. x          100      =          % of eosinophils
            Total WBC / cu.mm

Normal value: 0 – 4.5 x 109/liter


Thorn’s ACTH Test


This test is based on the fact that Adrenocorticoptropic Hormone (ACTH) produces in 4 hours a decrease by 50% or more in the eosinophil count of persons with a normally functioning adrenal cortex. It is useful as a diagnostic test in Addison’s disease, as a test for adrenal cortex reserve before surgical procedures, and a test to distinguish functional form organic disease of the adrenal cortex.


ABSOLUTE BASOPHIL COUNT                                                                                                    

Toluidine Blue Method (Cooper’s method)

Cetylpiridium chloride is used to lyse the erythrocytes and to render the basophil granules insoluble. Aluminum sulfate is used as a mordant to improve the staining qualities of toluidine blue. EDTA prevents platelet agglutination.

Staining solution:

            0.1% EDTA in saline solution – Solution I
            Cetylpiridium chloride (0.5%) – 25 ml
            Distilled water – 25 ml
            Toluidine blue (0.8%) in aluminum sulfate – 20 ml

Procedure:

0.08 ml of Solution I and 0.02 ml finger blood is mixed. Add 0.1 ml Solution II. Mix and stopper. Charge 2 Fuchs – Rosenthal chambers using a Pasteur pipette. Allow 5 minutes for the cells to settle.

Computation:

B in 16 big squares     x          5          =          B/cu.mm or ul
           16

Depth of the chamber – 0.2
Depth factor – 5
Volume in cu.mm – 3.2 (one section); 6.4 (2 sections)
No dilution employed so no dilution factor

Neutral Red Method

This is another staining method for basophils. But is has the following disadvantage:

1.     Eosinophils may also stain
2.     Basophil granules may be water soluble
3.     Platelet aggregates may interfere with the count

Indication of basophil count

1. Allergic conditions
2. Sensitization and anaphylaxis
Sensitization leads to an increase in the number of basophils which level too when the sensitization has occurred. If the patient is challenged with the same antigen, the count will fall at the rate depending on the type of reaction. Anaphylaxis leads to a rapid fall.

Normal values:           0 – 0.2 x 109/liter


RETICULOCYTE COUNT                                                                                                    

Reticulocytes are juvenile red cells; they contain remnants of the ribosomes and the ribonucleic acids which were present in larger amounts in the cytoplasm of the nucleated precursors from which they were derived. They possess a network known as reticular filamentous substance or granulo–filamentous substance which can be recognized on supravital staining. This characteristic is utilized for counting reticulocytes. The reticulum may be abundant or sparse depending on the maturation of the erythrocytes.

The number of reticulocytes in the peripheral blood is fairly accurate reflection of erythropoeitic activity, assuming that there is normal release of reticulocytes from the bone marrow, and that remain in circulation for the normal period of time.

The reticulocyte count can be made either with the use of dry or wet method.


Dry method:


The dry method consists of mixing blood and a special staining solution to stain the reticulocytes, using the mixture to make the smear, counterstaiing the smear with Wright’s stain, counting 1,000 red cells with the microscope, and calculating the % of reticulocytes.


Wet method:


The wet method consists of spreading a film of stain on a glass slide, adding a drop of blood, covering the preparation with a coverglass, counting 1,000 red cells with the microscope and calculating the % of reticulocytes.


Methods of reticulocyte count


1. New methylene blue

New Methylene Blue N method

New Methylene Blue N – 0.5 g
Potassium oxalate – 1.4 g
Sodium chloride – 0.8 g
Distilled water – 100 ml

2. Cook, Meyer and Tureen method

Solution A:      1% saline solution of Brilliant Cresyl Blue
Solution B:      1% saline solution of Potassium oxalate

3. Seiverd’s method

a.     1% physiologic saline solution of Brilliant Cresyl Blue
b.     1% methyl alcohol solution of Brillian Cresyl Blue
c.      New methylene blue N solution

4. Rapid method of Schilling

1% alcohol solution of Brilliant Cresyl Blue

5. Sabin’s method

a. Neutral red solution

Neutral red special – 125 mg
Neutral absolute ethyl alcohol – 50 ml

b. Janus Green solution

Janus green special – 125 mg
Neutral absolute alcohol – 62.5 ml

6. Osgood–Welhelm method

New Methylene Blue N method

Computation

            Number of retics counted     x          100      =          % Retics
            1000 red cells (retics & RBC)

            % Retics          x          RBC count/cu.mm      =          retics/cu.mm
                100

            Retics/cu.mm x          0.001               =                      x 109/liter

            Corrected Reticulocyte count:

            % Retics          x          Patient hematocrit     =          Corrected reticulocyte in %
                                                Norma hematocrit

            The normal hematocrit reading is taken to be 45%

            Normal values

                        0.5 – 1.5%                   or        5 – 15 x 10–3 / liter
            25,000 – 75,000          or        25 – 75 x 109/ liter

Importance of Reticulocyte count

1. To determine the response of the pernicious anemia patient to Vitamin B12 therapy
2. To aid in the diagnosis of hemolytic anemia and lead poisoning
3. To determine whether regeneration of erythrocytes is processing normally and whether it occurs at all that is of value in establishing a diagnosis of aplastic anemia.
4. To aid in the diagnosis of acute hemorrhage.

Reticulocyte is increased in: (Reticulocytosis)

1.     Hemolytic anemias
2.     Lead poisoning
3.     Malaria
4.     Parasitic infestations
5.     Toxic granulation

It is increased in

1.     Aplastic anemia
2.     Acute benzol poisoning
3.     Chronic infections


SIDEROCYTE COUNT                                                                                                                     

Siderocytes are erythrocytes containing granules which give a positive Prussian blue or Perls reaction for iron. The iron containing granules of siderocyte appear as basophilic granules. These granules are called Pappenheimer bodies when blood smears are obtained with Romanowsky stain (Wright’s solution) wherein they appear as basophilic rods or grains.

When the smears are first stained for reticulocytes with New Methylene Blue N and then stained with Safranin O, reticulum stains red and siderotic granules stain blue. Therefore, cell may be differentiated into those that:

a. Contain siderotic granules with no reticulum (siderocytes)
b. Those containing reticulum with no siderocytic granules (reticulocytes)
c. Those that contain both reticulum and siderotic granules (reticulated reticulocytes)

Prussian Blue or Perl’s reaction

Douglas or Dacie’s method

      Prussian blue reagent

      20% potassium ferrocyanide solution
      Concentrated HCl

      Safranin O counterstain

      Safranin O       –          0.5 grams
      Distilled water            –          100 ml

Computation:

No. of siderocytes and reticulated siderocytes x          100      =          % siderocytes
1000 red cells (includes siderocytes & reticulocytes

No. of retics and reticulated siderocytes                      
1000 red cells (includes siderocytes and retics  x          100      =          % reticulocytes

No. of siderocytes only (if only one stain was used)     x          100      =          % siderocytes
1000 red cells (including siderocytes)

The siderocyte stain is useful in differentiating anemia due to iron deficiency from anemia or thalassemia or other disorders in which iron accumulates because it is poorly utilized for hemoglobin synthesis.


PLATELET COUNT                                                                                                                          

Blood collection for platelet count

1. For best results, collect the blood with a 20 gauge needle and a siliconized syringe. Transfer the specimen to a small siliconized test tube which is kept cool either in an ice bath or in a refrigerator.

2. Capillary blood from a finger puncture may be diluted directly in a leukocyte or erythrocyte pipette.

3. Collect the blood in a non–siliconized syringe and transfer to a test tube containing EDTA.

Platelets are thin disks, 2 to 5 micrometers in diameter and 5 to 7 femtoliters in volume. They are small, colorless, moderately refractile bodies. When stained, they appear as azure granules with scanty blue cytoplasm.

Platelets are difficult to count because:

1. They are small and hard to distinguish from debris
2. They easily disintegrate
3. They have the tendency to adhere to glass, to any foreign body and particularly to each other

Methods of platelet count

1. Indirect method

In this method, platelets are counted in their relationship to red cells on a fixed smear. This is not reliable because the result depends upon the distribution of platelets and on the red blood cell count.

a. Fonio’s method

Stain used:            14% Magnesium sulfate
                              Wright’s stain

b. Dameshek’s method

Stain used:            Brilliant Cresyl Blue
                              Wright’s stain

c. Olef’s method

Formula

No. of platelets counted on the smear                    x          RBC count/mm3
1000 (red cells counted on the smear)

=          Platelet / cu.mm.

2. Direct method

In this method, the platelets are counted in the counting chamber as in leukocyte or erythrocyte count

a. Reese and Ecker’s method

Diluting fluid:       Sodium citrate – 3.8 g
                              Formalin – 0.9 ml
                              Brilliant Cresyl Blue – 0.1 g
                              Distilled water q.s.ad – 100 ml

b. Leake and Guy’s method

Diluting fluid:       Sodium oxalate – 1.6 g
                              40% Formalin – 94 ml
                              Crystal violet – 0.05 g
           
Computations:

If blood is diluted 1:20 with WBC pipette and 5 medium squares are counted, the formula is:

            No. of P seen in 5 squares     x          5          x          10        x          20
            =          P/cu.mm

If blood is diluted 1:200 with the RBC pipette and 4 big squares (WBC squares) are used, the formula is:

No. of P seen in 4 big squares           x          10        x          200      =          P/cu.mm
            4         

P/cu.mm         x          0.001   =          109/liter

c. Brecker–Cronkite method

In this method, the platelets are identified on the basis of their size, shape and structure with the use of phase – contrast microscope. The platelets under this type of microscope can easily be identified and readily distinguished from debris, precipitated stain and other foreign materials.

Diluting fluid:       1% ammonium oxalate
Ratio of dilution:  1:100

No. of P in 5 squares        x          5          x          10        x          100

=    P/cu.mm         x          0.001   =          x 109/liter

d. Electronic method of platelet counting

(1)   Voltage–pulse counting

Dilution:          1:3000            
                        3 ul blood plus 9 ml isoton or NSS

For platelelt count of less than 250,000/ul, the dilution is 1:300 – 20 ul plasma plus 6 ml diluent.

(2)   Electro–optical counting

Dilution:          1:1500 – in 2M area

Normal values

            Indirect method         250 – 500 x 109/liter
            Direct method                        150 – 450 x 109/liter

Sources of error

1.     Error in sampling
2.     Operator’s error
3.     Error in equipment and reagent
4.     Inherent error or field error

Physiologic variation

1. Platelet count is slightly lower at birth than in older children and adults

2. Platelet count may fall at the time of menstruation. 


No comments: