DAVAO DOCTORS COLLEGE

MEDICAL LABORATORY SCIENCE DEPARTMENT

STUDENT NOTES: HEMA 1
MIDTERM PART II
I. ERYTHROPOIESIS

-process by which erythroid precursor cells differentiate to become iii. The synthesis of heme begins in the mitochondria with the
mature RBC. The primary regulator of this process is erythropoietin. formation of D-ALA from glycine and succinyl coenzyme A.
It normally takes 3-5 days for the production of reticulocytes from
pronormoblasts. The reticulocytes remain in BM for 1-2 days before
being released to the circulation. In the peripheral circulation, the
reticulocyte continues to mature for one more day.

MATURATION

1. Pronormoblast / Rubriblast
a. 14-20 um diameter
b. Deeply basophilic cytoplasm
c. Non-granular
d. N/C ratio is 8:1
e. Fine chromatin
f. Usually 1-2 nucleoli
2. Basophilic Normoblast / Prorubricyte
a. 12-17 um diameter
b. intensely basophilic cytoplasm
c. N/C ratio is 6:1
d. Chromatin slightly coarse
e. Nucleoli are usually not visible
3. Polychromatophilic Normoblast / Rubricyte
a. 10-15 um diameter
b. blue-gray to pink-gray cytoplasm
c. N/C ratio is 4:1
d. Last stage of mitosis iv. The globin portion og Hgb is produced on specific ribosomes
4. Orthochromatophilic Normoblast / Metarubricyte in the cytoplasm of the RBC. The globin in each Hgb
a. 7-12 um diameter molecule consists of four polypeptide chains which determine
b. pink cytoplasm the type of hemoglobin formed.
c. N/C ratio is 2:1
d. Small pyknotic nucleus III. ABNORMAL HEMOGLOBIN
e. Last nucleated stage
5. Reticulocyte CarboxyHB (HbCO)  Hb bound to carbon monoxide
a. 7-10 um diameter  Hb affinity for CO is 200X greater
than its affinity to O2
b. pink to slightly pinkish gray cytoplasm
 Tobacco smokers: 1- 10% •
c. contains fine basophilic reticulum RNA, which is REVERSIBLE
d. only demostrated by supravital stain (NMB) MethHb / Hemiglobin (Hi)  Hb iron is in Fe+3 state
6. Mature RBC  Inherited: methHb reductase
a. 6-8 um diameter deficiency
b. pink in color  Acquired: exposure to chemicals
c. non-nucleated, round, biconcave like Chlorate, nitrite/nitrate
 Px is cyanotic; blood is chocolate
II. HEMOGLOBIN STRUCTURE AND SYNTHESIS brown
i. Primary function of the RBC is to manufucture Hgb, which in  Treatment: methelene blue or
turn, transports oxygen to the tissues and CO2 from tissue to ascorbic acid
lungs.  REVERSIBLE
ii. The Hgb molecule is composed of four subunits, each Sulfhemoglobin  Caused by chemical or
 drugs like aromatic amines or
containing heme and globin.
 sulfonamides hemorrhage and
 Can combine with CO to form hemolysis)
carboxysulfHb 3. CELL SHAPE
 IRREVERSIBLE - Poikilocytosis – variation in shape ; decrease ESR

IV. RBC ANOMALIES a. Poikilocytes Secondary to Membrane Abnormalities

1. CELL SIZE i. Acanthocyte/Spur Cell/Thorn Cell/Spike Cell
- Anisocytosis – variation in size - Spheroid with 3-12 irregular spikes or
- RDW – numerical expression that correlates with clublike spicules
the degree of anisocytosis. (NV: 11.5-14.5%) - Abnormal lipid ratios of membrane
i. Normocytic (MCV 80-100 fL) lecithins and sphingomyelins
- Clinical Significance: - IRREVERSIBLE
- Normal condition - Clinical Significance:
- Pathologic condition: a) Abetalipoproteinemia
a) Acute Post b) Alcoholic cirrhosis with HA
Hemorrhagic c) Hepatitis of newborn
Anemia d) Pyruvate kinase deficiency
b) Hemolytic Anemia e) Malabsorption states
c) Aplastic Anemia f) Postsplenectomy state
ii. Microcytic (MCV <80 fL) g) Severy HA assoc. with cirrhosis
- Clinical Significance: and metastatic liver disease
a) Iron Deficiency (spur cells)
Anemia ii. Echinocyte/Burr Cell/Crenated RBC/Sea
b) Thalassemia Urchin cell
c) Anemia of Chronic - Regular 10-30 scalloped short
Disease projections evenly distributed
iii. Macrocytic (MCV >100 fL) - Caused by: depletion of ATP, exposure
- Clinical Significance: to hypertonic solution and artifact in
a) Megaloblastic drying
Anemia - Clinical Significance:
b) Alcoholism a) Renal insufficiency (HUS)
c) Liver Disease iii. Codocyte/Target Cell/Mexican Hat Cell
2. HEMOGLOBIN CONTENT - Bell-shaped
- Anisochromia – variation in hemoglobin - Perioheral rim of Hb surrounded by
i. Normochromic (HCHC=31-36%) clear area and central hemoglobinized
- Seen in normal and area (bull’s eye)
pathologic conditions, A, H A. - Increases in cholesterol and
ii. Hypochromic phospholipid
- Central pallor area exceeds - Excess of surface membrane to
1/3 of the diameter of the volume ratio; decrease OFT
cell. - Clinical Significance:
- Clinical Significance: a) Hemoglobinopathies SS, CC,
a) Thalassemia DD, EE
b) Iron Deficiency b) Thalassemia
Anemia c) Obstructive liver disease
c) Chronic Blood Loss d) Postsplenectomy state
iii. Hyperchromic (MCHC= >36%) e) Iron deficiency anemia
- No central pallor <1/3 iv. Spherocyte/Bronze Cell
- C/C: SPHEROCYTOSIS - Decrease surface area:volume ratio
iv. Polychromasia - A. Spherocytosis – involves
v. Blue-gray coloration autoantibodies and hemolytic anemia
- Clinical Significance: - H. Spherocytosis – deficient spectrin
a) Indicates young (hallmark)
RBC - Increase OFT
b) Increased - Clinical Significance:
erythropoietic a) Hereditary Spehrocytosis
activity or b) Isoimmune and Autoimmune HA
reticulocytosis (ex. c) Severe BURNS
 d) Stored blood for long time b) Hereditary Pyropoikilocytosis
v. Stomatocyte iv. Semilunar bodies/Half-moon or Crescent
- Mouth or slit-like pallor area, bowl-shaped Cell)
in wet preparation. - Large, pale-pink staining ghost of the
- High cellular uptake of sodium and low red cell – the membrane remaining
potassium content. after the contents have been released.
- Abnormal Na+ -K+ transport ratio - Always acquired
- Clinical Significance: - Seen in MALARIA
a) Hereditary Stomatocytosis
b) Rh Null disease c. Poikilocytes Secondary to Abnormal Hb Content
c) Alcoholism i. Drepanocytes/Sickle Cells
d) Obstructive liver disease - Crescent-shaped
e) Cirrhosis - Polymerization of deoxygenated Hb
vi. Elliptocyte/Oat Cell - Clinical Significance:
- Rod or cigar-shaped, pencil or a) Sickle Cell Anemia
sausageshape, narrower than ovalocytes b) SC Disease
- Protein band 4.1 deficiency (hereditary
elliptocytosis) III. CRITERIA FOR RBC EVALUATION
- NOT associated with Hemolysis 1. Descriptive Terms
- Decrease lifespan but functions normally a. Variation in Size, Shape, or Color Content per
- OFT is normal OIO
vii. Ovalocyte i. Slight (<5%)
- Egg-like or oval shaped, wider than ii. Moderate (5-15%)
elliptocyte iii. Marked (>15%)
- Bipolar arrangement of Hb b. •Particular Size variation such as Macrocytes,
- Reduction of membrane cholesterol Poikilocytes, or Schistocytes
- Clinical Significance: i. Occasional (<1%)
a) Megaloblastic BM ii. Few (1-5%)
b) Myelodysplasia iii. Frequent (5-10%)
iv. Many (>10%)
b. Poikilocytes Secondary to Trauma
i. Schistocyte/Schizocyte/Keratocyte/Helmet/
Bite Cell
- Fragmentation produced by damage of
RBC by fibrin, altered vessel walls,
prosthetic heart valves.
- HALLMARK of HA secondary to red cell
fragmentation
- NOT Hereditary
- Clinical Significance:
a) DIC, TTP, BURNS
b) Microangipathic Hemolytic Anemia
ii. Dacryocyte/Dacrocyte (Teardrop Cell)
- Pear-shaped with blunt pointed projection
- Clinical Significance:
a) Myelofibrosis with Myeloid
Metaplasia (MMM)
b) Myelophthisic Anemia
c) Pernicious anemia
d) Tb
e) Tumor in BM
f) B-thalassemia
iii. Microspherocytes/Pyropoikilocytes
- Increase fragmentation at 45’C instead of
49’C
- Decrease MCV
- Clinical Significance:
a) Severe BURNS
IV. RBC INCLUSIONS i. Sideroblastic anemia
ii. MDS
1. Howell-Jolly Bodies iii. Thalassemia
a. Coarse densely stained purple granules, iv. HA
eccentrically located on periphery of membrane v. Defective erythropoiesis
b. Nuclear remnants of DNA – (+) Fuelgen 10. Malaria
c. Clinical Significance: a. Protozoan transmitted by bite of female
i. Megaloblastic Anemia b. Anopheles mosquito
ii. Severe hemolytic process 11. Babesia
iii. Thalessemia a. Protozoan inclusion (B. microti), transmitted from
iv. Accelerated erythropoiesis deer to humans by tick bite.
2. Basophilic Stippling
a. Dark blue granules V. MISCELLANEOUS
b. Precipitation of ribosomes and RNA
c. Clinical Significance: 1. . Autoagglutination – clumping of RBC
i. Lead poisoning a. Cold agglutinin syndrome
ii. Pyrimidine-5-nucleotidase deficiency i. PAP by M. pneumonia – anti I
iii. Heavy metal poisoning b. AIHA
iv. Thalassemia 2. Rouleaux – RBCs in stack of coin arrangement
3. Cabot Ring a. Multiply Myeloma
a. Rings, loops, figure of eight, red to purple b. Waldenstrom’s Macroglobulinemia
b. Remnant of microtubules of mitotic spindle
c. Clinical Significance: References:
i. Dyserythropoiesis
ii. Megaloblastic anemia Lotspeich-Steininger, C., Steine-Martin, E. A., Koepke, J., Clinical
4. Heinz Bodies Hematology, Principles, Procedures and Correlations, JB Lippincott
a. Deep purple irregularly shaped inculsions Company, East Washington Square, Philadelphia, Pennsylvania,
b. Precipitated, denatures Hb due to oxidative injury USA, 1992, pp 59-106
c. CANNOT be seen in Wright’s stain
Rodak, B., Fritsma, G., Keohane, L., Hematology, Clinical Principles
d. Requires supravital stain
and Applications, 4th Edition, 2012, Elsevier Saunders, Missouri,
e. Clinical Significance:
USA, pp 87-100
i. Hereditary defects in Hexose
ii. Monophosphate Shunt Denila, H., Hematology for Medical Laboratory Science, Philippines,
iii. G6PD deficiency pp 20-26
iv. Unstable Hemoglobins
5. Hemoglobin C Crystals
a. Tetragonal, rectangular rod shaped dense
staining crystals (bar of gold, clam shell)
b. Seen in Hb C disease
6. Hemoglobin SC Crystals
a. “washington monument” shape
7. Ringed Sideroblast
a. nRBC that contains nonheme iron particles
b. excessive iron overload in mitochondria of
normoblast
c. due to defective heme synthesis
d. Hemosiderin – needed for the identification
e. Clinical Significance:
i. Sideroblastic anemia
ii. MDS
8. Siderocyte
a. Non-nucleated cell containing iron granules
b. Seen in sideroblastic anemia and MDS.
9. Pappenheimer Bodies
a. Basophilic inclusions that aggregate in small
clusters near periphery with Wright’s stain.
b. Unused iron deposits.
c. Clinical Significance: