CBC, Peripheral Smear, Reticulocyte count, RBC indices, CRP, ESR, Blood Cell morphology

Question 1

is the process by which the formed elements of blood

are produced

Answer 1

Hematopoiesis

Question 2

In the bone marrow, the first morphologically recognizable erythroid precursor is the

Answer 2

pronormoblast. This cell can undergo four to five cell divisions, which result in the production of 16–32 mature red
cells.

Question 3

The mature red cell size

Answer 3

8 μm in diameter, anucleate, discoid in shape, and extremely pliable in order to traverse the microcirculation successfully; its membrane integrity
is maintained by the intracellular generation of ATP.

Normal red cell production results in the daily replacement of 0.8–1% of all circulating red cells in the body, since the average red cell lives 100–120 days. The organ responsible for red cell production is called the erythron.

The erythron is a dynamic organ made up of a rapidly proliferating pool of
marrow erythroid precursor cells and a large mass of mature circulating red blood cells.

Question 4

The physiologic regulator of red cell production, the glycoprotein hormone

Answer 4

EPO, is produced and released by peritubular capillary lining cells within the kidney

A small amount of EPO is produced by hepatocytes. The fundamental stimulus for EPO production is the availability of O2 for tissue metabolic needs

Question 5

Key to EPO gene regulation is

Answer 5

hypoxia-inducible factor (HIF)-1α. In the presence of O2, HIF-1α is hydroxylated at a key proline, allowing HIF-1α to be ubiquitinated and degraded via the proteasome
pathway.

Question 6

EPO level

Answer 6

the normal level being 10–25 U/L. When the hemoglobin concentration falls below
100–120 g/L (10–12 g/dL), plasma EPO levels increase in proportion to the severity of the anemia (Fig. 77-2).

In circulation, EPO has a half-clearance time of 6–9 h. EPO acts by binding to specific receptors
on the surface of marrow erythroid precursors, inducing them to proliferate and to mature

With EPO stimulation, red cell production can increase four- to fivefold within a 1- to 2-week period, but only in the presence of adequate nutrients, especially iron.

Question 7

mean hematocrit value for adult males and females is

Answer 7

47% (standard deviation, ±7%) and that for

adult females is 42% (±5%).

Any single hematocrit or hemoglobin value carries with it a likelihood of associated anemia.

Thus, a hematocrit of <39% in an adult male or <35% in an adult female has only about a 25% chance of being normal. Hematocrit levels are less useful than hemoglobin levels in assessing anemia because they are calculated rather than measured directly

Question 8

(WHO) defines anemia as a

Answer 8

hemoglobin level <130 g/L (13 g/dL) in men and <120 g/L (12 g/dL) in women

Question 9

If blood loss is mild, enhanced O2 delivery is achieved through changes in the O2–hemoglobin dissociation
curve mediated by a decreased pH or increased CO2

Answer 9

(Bohr effect).

Question 10

With acute blood loss, hypovolemia dominates the clinical picture, and the hematocrit and hemoglobin levels do not reflect the volume of blood lost.

Answer 10

Signs of vascular instability appear with acute losses of 10–15% of the total blood volume.

Question 11

% of the blood volume is lost suddenly, patients are unable to compensate with the usual mechanisms of vascular contraction and changes in regional blood flow. The patient prefers to remain supine and will
show postural hypotension and tachycardia

Answer 11

> 30

Question 12

(i.e., >2 L in the average-sized adult), signs of hypovolemic shock including confusion, dyspnea, diaphoresis, hypotension, and tachycardia appear

Answer 12

> 40%

Question 13

Intravascular hemolysis with release of free hemoglobin may be associated

Answer 13

with acute back pain, free hemoglobin in the plasma and urine, and renal failure.

Question 14

because of the intrinsic compensatory
mechanisms that govern the O2–hemoglobin dissociation curve, the gradual onset of anemia—particularly in young patients—may not be associated with signs or symptoms until the anemia is

Answer 14

severe

hemoglobin <70–80 g/L [7–8 g/dL]

Question 15

With chronic anemia, intracellular levels of ___ rise, shifting the dissociation curve to the right and facilitating O2 unloading. This compensatory
mechanism can only maintain normal tissue O2 delivery in the face of a 20–30 g/L (2–3 g/dL) deficit in hemoglobin concentration

Answer 15

2,3-bisphosphoglycerate

Question 16

Chronic inflammatory states (e.g., infection, rheumatoid arthritis, cancer) areassociated with

mild to moderate anemia

whereas lymphoproliferative
disorders, such as chronic lymphocytic leukemia and certain other B cell neoplasms, may be associated with

Answer 16

autoimmune hemolysis

Question 17

The skin and mucous membranes may be pale if the

hemoglobin is

Answer 17

<80–100 g/L (8–10 g/dL).

If the palmar creases are lighter in color than the surrounding skin when the hand is hyperextended, the hemoglobin level is usually <80 g/L (8 g/dL).

Question 18

High-normal hemoglobin values may be
seen in men and women who live at altitude or smoke heavily.
Hemoglobin elevations due to smoking reflect

Answer 18

normal compensation due to the displacement of O2 by CO in hemoglobin binding

Question 19

TIBC; an indirect measure of

Answer 19

serum transferrin),

Question 20

Microcytosis is reflected by a lower than normal MCV

Answer 20

(<80), whereas high values (>100) reflect macrocytosis

The MCH and MCHC reflect defects in hemoglobin synthesis (hypochromia)

Question 21

Mean cell volume (MCV) =

(hematocrit × 10)/(red cell
count × 10^6)

Answer 21

90 ± 8 fL

Question 22

Mean cell hemoglobin (MCH) =

(hemoglobin × 10)/(red
cell count × 10^6)

Answer 22

30 ± 3 pg

Question 23

Mean cell hemoglobin concentration =

(hemoglobin × 10)/hematocrit, or MCH/MCV

Answer 23

33 ± 2%

Question 24

As a complement to the red cell indices, the blood smear also reveals variations in cell size (anisocytosis) and shape (poikilocytosis).

Answer 24

Poikilocytosis suggests a defect
in the maturation of red cell precursors in the bone marrow or
fragmentation of circulating red cells. The blood smear may also
reveal 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,

Question 25

In the absence of a functional spleen, nuclear remnants are not culled from the red cells and remain as small homogeneously staining blue inclusions on Wright stain

Answer 25

Howell-Jolly bodies.

Question 26

Red cells may become fragmented in the presence of foreign bodies in the circulation, such as mechanical heart valves, or in the setting of thermal injury

Answer 26

Red cell fragmentation.

Question 27

Red cell changes in . The left panel | shows a teardrop-shaped cell.

Answer 27

myelofibrosis

Question 28

The red cells in uremia may acquire numerous regularly spaced, small, spiny projections. Such cells, called burr cells or echinocytes, are readily distinguishable from irregularly spiculated acanthocytes

Answer 28

Uremia.

Question 29

Spur cells are recognized as distorted red cells containing several irregularly distributed thornlike projections. Cells with this morphologic abnormality are also called

Answer 29

acanthocytes.

Question 30

This residual RNA is metabolized over the first 24–36 h of the reticulocyte’s life span in circulation. Normally, the reticulocyte count ranges from

Answer 30

1 to 2% and reflects the daily replacement of 0.8–1.0% of the circulating red cell population.

Question 31

if the EPO and erythroid marrow responses to moderate anemia [hemoglobin <100 g/L (10 g/dL)] are intact, the red cell production rate increases to two to three times normal within

Answer 31

10 days following the onset of anemia

Question 32

Correction #1 for Anemia: | This correction produces the corrected reticulocyte count.

Answer 32

In a person whose reticulocyte count is 9%, hemoglobin 7.5 g/dL, and hematocrit 23%, the absolute reticulocyte count = 9 × (7.5/15) [or × (23/45)] = 4.5% Note. This correction is not done if the reticulocyte count is reported in absolute numbers (e.g., 50,000/μL of blood)

Question 33

Correction #2 for Longer Life of Prematurely Released Reticulocytes in the Blood

Answer 33

This correction produces the reticulocyte production index. In a person whose reticulocyte count is 9%, hemoglobin 7.5 gm/dL, and hematocrit 23%, the reticulocyte production index 9x (7.5/15)(hemoglobin correction)/ 2( maturation time concentration) = 2.25

Question 34

Erythroid cells take

Answer 34

∼4.5 days to mature.

Question 35

The normal serum iron ranges

Answer 35

from 9 to 27 μmol/L (50–150 μg/dL), whereas the normal TIBC is 54–64 μmol/L (300–360 μg/dL); the normal transferrin saturation ranges from 25 to 50%. A diurnal variation in the serum iron leads to a variation in the percent transferrin saturation.

Question 36

Adult males have serum ferritin levels that average

Answer 36

∼100 μg/L, corresponding to iron stores of ∼1 g. Adult females have lower serum ferritin levels averaging 30 μg/L, reflecting lower iron stores (∼300 mg). A serum ferritin level of 10–15 μg/L indicates depletion of body iron stores

Question 37

ferritin is also an acute-phase reactant and, in the presence of acute or chronic inflammation, may rise several-fold above baseline levels. As a rule, a serum ferritin >

Answer 37

200 μg/L means there is at least some iron in tissue stores

Question 38

A patient with a hypoproliferative anemia and a reticulocyte production index <2 will demonstrate an M/E ratio of 2 or 3:1. In contrast, patients with hemolytic disease and a

Answer 38

Reticulocyte production index >3 will have an M/E ratio of at least 1:1 Erythroid hyperplasia. This marrow shows an increase in the fraction of cells in the erythroid lineage as might be seen when a normal marrow compensates for acute blood loss or hemolysis. The myeloid/erythroid (M/E) ratio is about 1:1. Myeloid hyperplasia. This marrow shows an increase in the fraction of cells in the myeloid or granulocytic lineage as might be seen in a normal marrow responding to infection. The myeloid/ erythroid (M/E) ratio is >3:1

Question 39

On carefully prepared bone marrow smears, small ferritin granules can normally be seen under oil immersion in 20–40% of developing erythroblasts. Such cells are called

Answer 39

sideroblasts

Question 40

Normal Bone Marrow cells

Answer 40

Note that the nucleated cellular elements account | for ∼40–50% and the fat (clear areas) accounts for ∼50–60% of the area.

Question 41

a reticulocyte production index >2.5 indicates that

Answer 41

hemolysis is most likely A reticulocyte production index <2 indicates either a hypoproliferative anemia or maturation disorder.

Question 42

% of all cases of anemia are hypoproliferative in nature

Answer 42

At least 75%

Question 43

Polycythemia

Answer 43

Concern that the hemoglobin level may be abnormally high is usually triggered at 170 g/L (17 g/dL) for men and 150 g/L (15 g/dL) for women

Question 44

Anemias associated with normocytic and normochromic red cells and an inappropriately low reticulocyte response (reticulocyte index <2–2.5) are

Answer 44

hypoproliferative anemias

Question 45

Normally 80% of iron passing through the plasma transferrin pool is recycled from senescent red cells. Absorption of approximately

Answer 45

1 mg/d is required from the diet in men, and 1.4 mg/d in women to maintain homeostasis. As long as transferrin saturation is maintained between 20 and 60% and erythropoiesis is not increased, use of iron stores is not required Normally, the iron bound to transferrin turns over 6–8 times per day. Assuming a normal plasma iron level of 80–100 μg/dL, the amount of iron passing through the transferrin pool is 20–24 mg/d.

Question 46

Normal blood leukocyte counts are

Answer 46

4.3–10.8 × 109/L, with ``` neutrophils 45–74% bands 0–4%, lymphocytes 16–45% monocytes 4–10% eosinophils 0–7% basophils 0–2%. ```

Question 47

WBC morphology

Answer 47

MYELOBLAST- Prominent nucleoli PROMYELOCYTE-Large cell Primary granules appear MYELOCYTE- Secondary granules appear METAMYELOCYTE- Kidney bean– shaped nucleus NEUTROPHIL-Condensed, multilobed nucleus

Question 48

The primary granules contain hydrolases, elastase, myeloperoxidase, cathepsin G, cationic proteins, and bactericidal/ permeability-increasing protein, which is important for killing gram-negative bacteria.

Answer 48

Azurophil granules also contain defensins, a family of cysteine-rich polypeptides with broad antimicrobial activity against bacteria, fungi, and certain enveloped viruses.

Question 49

Secondary granule

Answer 49

contents are readily released extracellularly, and their mobilization is important in modulating inflammation

Question 50

severe acute bacterial infection, prominent neutrophil cytoplasmic granules, called

Answer 50

toxic granulations, are occasionally seen. Toxic granulations are immature or abnormally staining azurophil granules

Question 51

Cytoplasmic inclusions, also called

Answer 51

Döhle bodies can be seen during infection and are fragments of ribosome-rich endoplasmic reticulum. Döhle bodies are discrete, blue-staining, nongranular areas found in the periphery of the cytoplasm of the neutrophil in infections and other toxic states

Question 52

In this benign disorder, the | majority of granulocytes are bilobed. The nucleus frequently has a spectacle-like, or “pince-nez,” configuration.

Answer 52

Pelger-Hüet anomaly

Question 53

The best place to examine blood cell morphology is the

Answer 53

feathered edge of the blood smear where red cells lie in a single layer, side by side, just barely touching one another but not overlapping

Question 54

The platelets are usually ___ diameter

Answer 54

1–2 μm in diameter and have a blue granulated appearance. There is usually 1 platelet for every 20 or red cells Large platelets may be a sign of rapid platelet turnover,

Question 55

RBC size

Answer 55

One can gauge their size by comparing the red cell to the nucleus of a small lymphocyte. Both are normally about 8 μm wide. Red cells that are smaller than the small lymphocyte nucleus may be microcytic; those larger than the small lymphocyte nucleus may be macrocytic.

Question 56

Macrocytic cells also tend to be more oval than spherical in shape and are sometimes called macroovalocytes.

Answer 56

The automated mean corpuscular volume (MCV) can assist in making a classification. However, some patients may have both iron and vitamin B12 deficiency, which will produce an MCV in the normal range but wide variation in red cell size

Question 57

When the red cells vary greatly in size, anisocytosis is said to be present.

Answer 57

When the red cells vary greatly in shape, poikilocytosis is said to be present. The electronic cell counter provides an independent assessment of variability in red cell size. It measures the range of red cell volumes and reports the results as “red cell distribution width” (RDW) This value is calculated from the MCV; thus, cell width is not being measured but cell volume is The width of the red cell volume distribution curve is what determines the RDW

Question 58

The RDW is calculated as follows:

Answer 58

RDW = (standard deviation of MCV ÷ mean MCV) × 100. In the presence of morphologic anisocytosis, RDW (normally 11–14%) increases to 15–18%.

Question 59

In patients with microcytic anemia, the differential diagnosis is generally between iron deficiency and thalassemia.

Answer 59

In thalassemia, the small red cells are generally of uniform size with a normal small RDW. In iron deficiency, the size variability and the RDW are large a large RDW can suggest a dimorphic anemia when a chronic atrophic gastritis can produce both vitamin B12 malabsorption to produce macrocytic anemia and blood loss to produce iron deficiency. RDW also has been reported as a risk factor for all-cause mortality in population-based studies They are never “hyperchromic.” If more than the normal amount of hemoglobin is made, the cells get larger—they donot become darker.

Question 60

—diffuse fine or coarse blue dots in the red cell | usually representing RNA residue—especially common in lead poisoning

Answer 60

Basophilic stippling

Question 61

—dense blue circular inclusions that represent | nuclear remnants—their presence implies defective splenic function

Answer 61

Howell-Jolly bodies

Question 62

—red cells may be released or pushed out of the marrow prematurely before nuclear extrusion—often implies a myelophthisic process or a vigorous narrow response to anemia, usually hemolytic anemia

Answer 62

Nuclei

Question 63

—the red cell cytoplasm has a bluish hue, reflecting the persistence of ribosomes still actively making hemoglobin in a young red cell

Answer 63

Polychromatophilia

Question 64

Vital stains are necessary to see precipitated hemoglobin called

Answer 64

Heinz bodies.

Question 65

Small red cells without the central | pallor are

Answer 65

spherocytes; they can be seen in hereditary spherocytosis, hemolytic anemias of other causes, and clostridial sepsis

Question 66

____are teardrop-shaped cells that can be seen in hemolytic anemias, severe iron deficiency, thalassemias, myelofibrosis, and myelodysplastic syndromes.

Answer 66

Dacrocytes A teardrop-shaped red blood cell (left panel) and a nucleated red blood cell (right panel) as typically seen with myelofibrosis and extramedullary hematopoiesis

Question 67

___ helmet-shaped cells that reflect microangiopathic | hemolytic anemia or fragmentation on an artificial heart valve

Answer 67

Schistocytes

Question 68

___ spiculated red cells with the spikes evenly spaced; they can represent an artifact of abnormal drying of the blood smear or reflect changes in stored blood. They also can be seen in renal failure and malnutrition and are often reversible.

Answer 68

Echinocytes Echinocytes are found in patients with severe uremia, in glycolytic red cell enzyme defects, and in microangiopathic hemolytic anemia.

Question 69

are spiculated red cells with the spikes irregularly distributed. This process tends to be irreversible and reflects underlying renal disease, abetalipoproteinemia, or splenectomy

Answer 69

Acanthocytes Acanthocytes are present in severe liver disease, in patients with abetalipoproteinemia, and in rare patients with McLeod blood group

Question 70

are elliptical-shaped red cells that can reflect an inherited defect in the red cell membrane, but they also are seen in iron deficiency, myelodysplastic syndromes, megaloblastic anemia, and thalassemias

Answer 70

Elliptocytes Elliptical shape of red cells is related to weakened membrane structure, usually due to mutations in spectrin

Question 71

___ are red cells in which the area of central pallor takes on the morphology of a slit instead of the usual round shape

Answer 71

Stomatocytes Stomatocytes can indicate an inherited red cell membrane defect and also can be seen in alcoholism This often is seen as an artifact in a dehydrated blood smear. These cells can be seen in hemolytic anemias and in conditions in which the red cell is overhydrated or dehydrated

Question 72

___have an area of central pallor that contains a dense center, or bull’s-eye

Answer 72

Target cells These cells are seen classically in thalassemia, but they are also present in iron deficiency, cholestatic liver disease, and some hemoglobinopathies. They also can be generated artifactually by improper slide making Small numbers of target cells are seen with liver disease and thalassemia. Larger numbers are typical of hemoglobin C disease

Question 73

Some patients have red cell clumping (called

Answer 73

agglutination) in which the red cells pile upon one another; it is seen in certain paraproteinemias and autoimmune hemolytic anemias. Another abnormal distribution involves red cells lying in single cell rows on top of one another like stacks of coins. This is called rouleaux formation and reflects abnormal serum protein levels.

Question 74

___are generally the most abundant white cell. They are round, are 10–14 μm wide, and contain a lobulated nucleus with two to five lobes connected by a thin chromatin thread.

Answer 74

Neutrophils Bands are immature neutrophils that have not completed nuclear condensation and have a U-shaped nucleus. Bands reflect a left shift in neutrophil maturation in an effort to make more cells more rapidly Vacuolated neutrophils may be a sign of bacterial sepsis.

Question 75

in WBC | The presence of 1- to 2-μm blue cytoplasmic inclusions, called

Answer 75

Döhle bodies, can reflect infections, burns, or other inflammatory states. If the neutrophil granules are larger than normal and stain a darker blue, “toxic granulations” are said to be present, and they also suggest a systemic inflammation Döhle body. Neutrophil band with Döhle body. The neutrophil with a sausage-shaped nucleus in the center of the field is a band form. Döhle bodies are discrete, blue-staining nongranular areas found in the periphery of the cytoplasm of the neutrophil in infections and other toxic states. They represent aggregates of rough endoplasmic reticulum.

Question 76

The presence of neutrophils with more than five nuclear lobes suggests

Answer 76

Megaloblastic anemia. Large misshapen granules may reflect the inherited Chédiak-Higashi syndrome

Question 77

____are slightly larger than neutrophils, have bilobed nuclei, and contain large red granules.

Answer 77

Eosinophils Diseases of eosinophils are associated with too many of them rather than any morphologic or qualitative change.

Question 78

___are even rarer than eosinophils in the blood. They have large dark blue granules and may be increased as part of chronic myeloid leukemia

Answer 78

Basophils .

Question 79

In the presence of viral infections, more of the lymphocytes are larger, about the size of neutrophils, with abundant cytoplasm and a less condensed nuclear chromatin. These cells are called

Answer 79

reactive lymphocytes About 1% of lymphocytes are larger and contain blue granules in a light blue cytoplasm; they are called large granular lymphocytes.

Question 80

chronic lymphoid leukemia, the small lymphocytes are increased in number, and many of them are ruptured in making the blood smear, leaving a smudge of nuclear material without a surrounding cytoplasm or cell membrane; they are called

Answer 80

smudge cells and are rare in the absence of chronic lymphoid leukemia.

Question 81

___are the largest white blood cells, ranging from 15 to 22μm in diameter. The nucleus can take on a variety of shapes but usually appears to be folded; the cytoplasm is gray

Answer 81

Monocytes

Question 82

(multilobed polymorphonuclear leukocytes) are larger | than normal neutrophils with five or more segmented nuclear lobes.

Answer 82

Hypersegmented neutrophils They are commonly seen with folic acid or vitamin B12 deficiency.

Question 83

Spiculated red cells are of two types:

Answer 83

acanthocytes are contracted dense cells with irregular membrane projections that vary in length and width; echinocytes have small, uniform, and evenly spaced membrane projections

Question 84

__together with a marked increase in the platelet count, are seen in myeloproliferative disorders,

Answer 84

Giant platelets, especially primary thrombocythemia.

Question 85

The percentage of the | space that consists of hematopoietic cells is referred to as

Answer 85

marrow cellularity. In adults, normal marrow cellularity is 35–40%. If demands for increased marrow production occur, cellularity may increase to meet the demand. As people age, the marrow cellularity decreases and the marrow fat increases. Patients >70 years old may have a 20–30% marrow cellularity.

Question 86

Marrow aspirate specimen with a myeloid/erythroid ratio (M/E ratio) of 1:1–2, typical for a patient with a hemolytic anemia or one recovering from blood loss.

Answer 86

Erythroid hyperplasia of the marrow.

Question 87

Marrow aspirate specimen showing a myeloid/erythroid ratio of ≥3:1, suggesting either a loss of red blood cell precursors or an expansion of myeloid elements.

Answer 87

Myeloid hyperplasia of the marrow.

Question 88

An orthochromatic normoblast with a collar of blue granules (mitochondria encrusted with iron) surrounding the nucleus.

Answer 88

Ringed sideroblast.

Question 89

Note prominent | cytoplasmic granules in the leukemia cells.

Answer 89

Acute promyelocytic leukemia.

Question 90

Peripheral blood smear showing | leukemia cells with typical “flower-shaped” nucleus

Answer 90

Adult T cell leukemia.

Question 91

Lymphocytes with frequently convoluted nuclei (Sézary cells) in a patient with advanced mycosis fungoides.

Answer 91

Sézary’s syndrome.

Question 92

A Reed-Sternberg cell is present near the center of the field; a large cell with a bilobed nucleus and prominent nucleoli giving an “owl’s eyes” appearance. The majority of the cells are normal lymphocytes, neutrophils, and eosinophils that form a pleiomorphic cellular infiltrate

Answer 92

Hodgkin’s disease.

Question 93

Erythrocyte sedimentation rate

Answer 93

Females: 0–20 mm/h Males: 0–15 mm/h

Question 94

with low-grade fevers or | possible disease, the most valuable measurements are

Answer 94

the C-reactive protein level and the erythrocyte sedimentation rate. These markers of inflammatory processes are particularly helpful in detecting occult disease. Measurement of circulating IL-6 is useful because IL-6 induces C-reactive protein The erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) level are indirect and direct measures of the acute-phase response, respectively, these markers can be followed serially over time to monitor disease

Question 95

It is noteworthy that the ESR changes relatively

Answer 95

slowly, and its measurement more often than weekly usually is not useful; in contrast, CRP concentrations change rapidly, and daily measurements can be useful in the appropriate context. An extremely elevated ESR (>100 mm/h) has a 90% predictive value for a serious underlying disease (Table 144-3). Work is ongoing to identify other potentially useful inflammatory markers (e.g., procalcitonin, serum amyloid A protein);

Question 96

Causes of an Extremely Elevated Erythrocyte | Sedimentati on Rate (>100 mm/h)

Answer 96

Infectious diseases (35–40) Inflammatory diseases (15–20) Malignancies (15–20) Other (20–35)