normal and abnormal barrett w. dick, m.d. director, hematology laboratories memorial medical center...
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ERYTHROPOIESISNormal and abnormal
Barrett W. Dick, M.D.Director, Hematology LaboratoriesMemorial Medical CenterSpringfield. IL Clinical Professor, Pathology and MedicineSouthern Illinois School of Medicine
RBC development
Increasing cytoplasmic hemoglobin
Decreasing cytoplasmic RNA
POLYCHROMATOPHILIA VS. NORMAL
Immature red cells are bigger, bluer and have less central pallor than mature rbc.
NOTE: On the left is a diagrammatic representation of a young red cell, usually described as “polychromatophilic”. Note that it is larger and bluer than a mature red cell on the right. This is due to its RNA content.
Reticulocytes vs. Polychromasia
Reticulocytes vs. Polychromasia
Reticulocytes require special techniques for measurement
The two terms are not equivalent but frequently, but incorrectly, used as equivalent
Estimating polychromasia from a stained blood smear is not a substitute for performing a reticulocyte count. The correlation is poor.
Increased Polychromasia
Polychromatophilic Rbc
Blood Smear Examination
Too thick Too thin
Area behind “feather edge”-
Just right.
Smear ExaminationFeather EdgeThin Area
Low Power Examination Of Blood Smear
Performed at 10X magnification Evaluate quality of smear- appropriate thin area Check for increased rouleaux formation Scan for white cell distribution- even With practice can estimate the white count and
differential: at very least make sure they correlate with machine count and/or manual diff
Thin Area of Smear
10X mag
Ideal Area of Blood Smear
Red cells close, evenly spaced without significant overlapping
50X Oil
Increased Rouleaux Formation
Some degree of rouleaux formation is normal; this is increased
High Power Examination
Scan performed at no lower than 40X coverslipped smear or 50X oil Estimate the differential and look for
qualitative Wbc abnormalities Rbc morphology Platelet estimate
Perform a differential at 100X if specimen has been flagged as being abnormal- 200 cells.
Normal Rbc
Rbc variation
Anisocytosis- Variation in size Poikilocytosis- Variation in shape
Slight variation of size and shape is normal. When abnormalities are reported, what it should mean is that more than normal variation is present.
Normal Size Distribution
50 100 200RBC
NOTE: This illustrates a normal red cell distribution with the horizontal scale representing cubic micra. The RDW is by convention a mathematical expression of the width of the curve near the base.
Red Cell Size
Red cell size can only be measured accurately using electronic instrumentation to measure the volume (MCV).
On blood smear examination, the size estimate is based on diameter, which is not very accurate and does not correlate well with the MCV
Small lymphocyte nuclei are a rough guide to normal Rbc diameter
Microcytic Rbc
7.5 mu
Avr.diameter of normal Rbc= 7.5 mu
Microcytic, Hypochromic Rbc
Microcytic Hypochromic Rbc
Hypochromia is the most frequently overcalled abnormality on blood smears, usually due to technical factors
When real, usually due to advanced iron deficiency Men: Hgb<10g/dl Women: Hgb<8g/dl
Rarely in our population- thalassemia major
Macrocytic Rbc
This smear also illustrates increased variation in size (anisocytosis) and increased variation in shape (poikilocytosis).
Abnormal red cell shapes- poikilocytosis
Elliptocytes (ovalocytes)
Elliptocytes are a common non-specific abnormality. Hereditary elliptocytosis is also relatively common and is usually not hemolytic. The hereditary form is more common in peoples of African origin
Burr Cells, Acanthocytes, Crenated Cells
Terms that are frequently, but incorrectly, used interchangeably. When strictly defined the terms can have specific clinical correlations.
Acanthocyte
Burr Cell Crenated Rbc
Burr Cells
Burr cells have rounded, blunt projections at the edges and have central pallor
Burr Cells
Uremia Liver disease Metabolic
imbalance
Acanthocytes
Acanthocytes look like spherocytes with irregularly spaced, thin, spiny projections
Acanthocyte
Differential Dx for Acanthocytes
Liver Disease Post-Splenectomy aBeta
lipoproteinemia
Crenated Red Cells
Crenated red cells have the appearance of sea urchin eggs: short, evenly-spaced, broad-based spikes projecting in three dimensions. They are seen in some severely ill patients with marked electrolyte abnormalities. In a reference laboratory setting, they are a frequent manifestation of a poorly preserved specimen..
Post-Splenectomy
Howell-Jolly Bodies Acanthocytes Target Cells Lymphocytosis
Post-Splenectomy
Howell-Jolly Body
Target Cells
Target Cells
Liver disease and/or hyperbilirubinemia
Post-splenectomy Hemoglobinopathies
Hemoglobin C syndromes:▪ AC, SC, C-thal▪ NOT thalassemia minor, <1% of cases
Spherocytes
The cells are small in diameter but not in volume. Because of their spherical shape they do not flatten on the slide.
Differential Dx- Spherocytes
Hereditary Spherocytosis Autoimmune hemolysis Alloimmune hemolysis-
Newborns with ABO incompatibility Delayed transfusion reactions
Thermal injury- burn patients Occasionally- non-specific with
transfused red cells
Osmotic Fragility Test
Microspherocytes secondary to severe thermal injury
Tear Drop Cells
Common in disorders associated with marrow infiltration and splenomegaly
Coarse Basophilic Stippling
Coarse stippling is usually associated with some form of dyserythropoeisis.
Schistocytes- Rbc fragments, so-called “Microangiopathic Hemolytic Anemias”
TTP /HUS Vasculitis Partially thrombosed vessels including
heart chambers Sever cardiac valve abnormalities or
malfunctioning prosthesis DIC- rarely; most often associated with
chronic DIC
Schistocytes
Schistocytes- Rbc fragments
Pocked (Pitted”) Red Cells
These cells look like spherocytes with bites in the edges, aka, “bite” cells. This is due to removal of denatured hemoglobin by the pitting function of the spleen
Heinz Body Hemolytic Anemias
Heinz Bodies are denatured hemoglobin usually due an oxidant. They are removed by the spleen causing deformed rbc- “pitted” rbc, aka “pocked” or “bite” cells
Hereditary G6PD deficiency: hemolysis is usually drug
induced or can be induced non-specifically by stress, such as infection
Unstable hemoglobins Acquired: oxidant drug-induced without a hgb
or enyzmatic abnormality
Common Hemoglobinopathies with Peripheral Blood Abnormalities
Thalassemia minor- microcytosis with mild or no anemia; worldwide in distribution
Hemoglobin AC- Target cells, sometimes spherocytes (few); from West Africa
Hemoglobin AE or EE- Microcytosis and target cells with minimal or no anemia: from SE Asia
Hemoglobin SS- Sickle cells with variable anemia
Hemoglobin SC- Target cells, spherocytes, sometimes sickle cells depending on the severity; may be asymptomatic
Thalassemia minor
Mild or no anemia with microcytosis. The prevalence of target cells in this disorder is markedly overstated in texts and in the literature
Sickle Cell Anemia
S-C Disease
SC crystals have a characteristic appearance with blunted, rhomboidal ends
Screening for Hemoglobinopathies
Thal minor CANNOT be diagnosed by Hgb electrophoresis in the overwhelming majority of patients; it is a diagnosis of exclusion: R/O iron deficiency
Hemoglobin electrophoresis is the procedure of choice for testing for other hemoglobin abnormalities; quick tests are not recommended
Screening for Hemoglobinopathies
A F S A2 D C G E
Malaria
Malaria
Malaria
Platelet overlying a red cell
These are frequently mistaken for malaria parasites