Bisc 341 - Hematology - Test 2

Front 1

Objectives of first anemia ppt:

Back 1

Describe the characteristics and significance of the following classes of anemias and identify the most common examples of each class:

*Megaloblastic anemias

*Hemolytic anemias - both inherited and acquired

Describe the diagnostic roles of folic acid assay, Vitamin B12 assay, Reticulocyte count, ESR, and Hemoglobin electrophoreisis

Front 2

Megaloblastic anemias have two major divisions. What are they?

Back 2

Vitamin B12 Deficiency and Folic Acid Deficiency

Front 3

What does Megaloblastic refer to?

Back 3

Abnormal bone marrow red cell precursors that show altered DNA synthesis; very large blood cells because DNA synthesis is inhibited and the cell continues growing without division.

Front 4

What are the characteristics of red cells in megaloblastic anemia?

Back 4

Abnormal nuclear maturation

Imbalance between nuclear and cytoplasmic maturation (n/c ratio?)

This is bc the absense of B12 or Folate impairs DNA synthesis, slowing down each step of maturation.

Front 5

What are some cellular results of megaloblastic anemia?

Back 5

Large nucleus, increased cytoplasmic RNA, early hemoglobin synthesis

Many cells never undergo mitosis and breakdown in bone marrow, so serum LDH is increased

Front 6

What other cell types does Megaloblastic anemia affect?

Back 6

Myelogenous white cells, megakaryocytes (producing leukopenia and neutrophilic hypersegmentation and thrombocytopenia)

Front 7

True or False: Megakaryocyte fragments and giant platelets can be seen on peripherial blood smears

Back 7

True

Front 8

What type of Anemia is depicted in this image?

Back 8

Megaloblastic Anemia

Front 9

True or False: Neurological symptoms are rate in megaloblastic anemia

Back 9

False; they are common. They may even occur in the absence of hematological symptoms.

Front 10

How is megaloblastic anemia diagnosed?

Back 10

Serum Cobalamin (B12) or Folate is measured

Front 11

Megaloblastic Anemia caused by B12 deficiency is associated with these disorders:

Back 11

-Parasitic infection (D. latum), which causes increased cobalamin (B12) usage

-Malabsorption syndromes

-Nutritional deficiency

-Pernicious anemia, associated with chronic atrophic gastritis (disease with auto-antibodies to intrinsic factor which is needed to absorb B12)

BASICALLY, something is stopping B12 from being absorbed, it is not consumed enough.

Front 12

Megaloblastic Anemia caused by folic acid deficiency is associated with:

Back 12

-Abnormal absorption

-Increased utilization (pregnancy)

-Treatment with antimetabolites that act as folic acid antagonists

BASICALLY, not absorbed enough, overused, or depleted by drugs

Front 13

Normal red cell maturation relies on two factors. What are they?

Back 13

Vitamin B12, Folate

Front 14

Where does Vitamin B12 occur?

Back 14

Naturally, in meats, eggs, and dairy.

Front 15

Where are folates found?

Back 15

Yeast, leafy vegetables, organ meats

Front 16

What is the most common megaloblastic anemia?

Back 16

Pernicious anemia; its laboratory findings are similar to other types of megaloblastic anemias and will look the same regardless of cause (B12 or folic acid deficiency)

Front 17

True or False: In megaloblastic anemia, Hemoglobin and red counts are extremely high

Back 17

False, they are extremely low.

Front 18

How is hematocrit affected by megaloblastic anemia? (MCV, MCH, MCHC)

Back 18

Hematocrit may not reflect the actual red cell decrease because the cells are so large.

MCV - as high as 130 (normal: 80-100)

MCH - varies, but is usually increased (normal: 27-31)

MCHC - usually normal (normal: 32-26)

Front 19

How does megaloblastic anemia affect platelets?

Back 19

Platelet counts are moderately decreased

Front 20

How are white cells affected by megaloblastic anemia?

Back 20

Leukopenia, usually neutropenia (low WBC count, particularly neutrophils that fight bacterial and fungal infections)

Front 21

What would a megaloblastic anemia smear look like? Describe the features.

Back 21

-Moderate to significant anisocytosis (blood cells are unequal in size) and poikilocytosis (abnormally shaped blood cells), with many macrocytes (large cells) and ovalocytes (oval shaped and hgb rich)

-Erythroid precursors, mostly metarubicytes (nucleated RBC)

-Red cell inclusions such as basophilic stippling, Howell-Jolly bodies, and Cabot Rings

-Leukocytes show hypersegmentation and an increase in eosinophils

-Platelets may be decreased with giant forms present

-Reticulocyte count is low

-Pancytopenia will occur in advanced cases (reduction in red cells, white cells, platelets)

-Dimorphic red cell population w/ high RDW (red cell distribution width)

Front 22

What type of anemia is this?

Back 22

Megaloblastic anemia

Front 23

What occurs in the bone marrow as a result of megaloblastic anemia?

Back 23

-Hypercellular with megaloblastic changes in the erythroid line or all lines

-RBC precursors are enlarged with decreased n/c ratio

-Giant metamyelocytes with large, incompletely segmented nuclei

-Increased iron stores

Front 24

What are the chemistry results for megaloblastic anemia cases? Consider LDH, bilirubin, and uric acid levels.

Back 24

-Extremely high LDH

-Increased unconjugated bilirubin (due to intramedullary hemolysis)

-Uric acid levels are low, secondary to decreased DNA synthesis

Front 25

What tests can be performed to diagnose megaloblastic anemia?

Back 25

-Vitamin B12 assay

-Folate Assay

-Schilling test (to detect B12 and intrinsic factor deficiency)

[Radio-labeled B12 is given. If the urine specimen shows little radio-label, then there is a B12 deficiency. If radio-label appears in urine, a second test is given. If the urine is clear, the diagnosis is pernicious anemia. If radiolabel appears in the urine, there is a malabsorption syndrome]

Front 26

How is megaloblastic anemia treated?

Back 26

-The patient is given B12 or folate

-After treatment, the reticulocyte count begins to increase in 2-3 days and it will peak at 5-8 days.

-Hematocrit will begin to increase in 1 week and will normalize in 4-8 weeks.

Front 27

What is hemolytic anemia characterized by?

Back 27

-An increase in red cell destruction, initiated primarily by cells being trapped in the liver or spleen. This produces a decrease in the normal erythrocyte lifespan.

Front 28

What is the bone marrow response to increased red cell destruction?

Back 28

Increased bone marrow activity will occur to compensate for the decrease of red cells. If the bone marrow fails to keep up with the red cell destruction, anemia develops.

Front 29

Hemolysis of the red cell involves the alteration of the membrane. The causes for this alteration can be divided into two categories. What are they?

Back 29

-Intrinsic hemolytic anemia (inherited)

-Extrinsic hemolytic anemia (outside factors affected the cell)

Front 30

Describe the destruction sites of red cells.

Back 30

Intravascular (within circulating blood) or extravascular (outside circulating blood)

Front 31

List some causes of inherited hemolytic anemia.

Back 31

-Membrane defects (Heriditary spherocytosis [spherical blood cells], elliptocytosis [ellipse shaped blood cells], stomatocytosis [blood cells are leaky], Rh null disease)

-Enzyme defects (G6PD deficiency [favism, normally protects red blood cells), pyruvate kinase deficiency, methemoglobin reductasse deficiency [ferric rather than ferrous hbg; difficulty releasing oxygen to tissues])

BASICALLY, can affect membrane structure, enzymes, or hemoglobin molecule

Front 32

Normal red cell membranes allow the cell to be flexible, resilient, and undergo numerous passages through the spleen. They normally survive for 120 days. When the cell membrane becomes instable and inflexible, what happens?

Back 32

The spleen must remove the cell. The rate of hemolysis is increased and will exceed the bone marrow's ability to replace the cells. Anemia will occur.

Front 33

The ability of a red cell to deform and return to normal is determined by:

Back 33

-Membrane flexibility (structure and functional integrity of membrane skeleton)

-Cytoplasmic viscosity (determined by hbg)

-Cell surface area to volume ratio

Front 34

-In this disorder, cases can range from almost normal trait carriers to severe anemics.

-A membrane protein defect can cause a loss of portions of RBC membrane.

-Hemolysis is extravascular, occurring only in the spleen.

-Decreased surface area to volume ratio causes the cell to deform (reduced flexibility)

-Abnormal permeability to Na+ ions, allowing lots of sodium in (10x)

Back 34

Heriditary spherocytosis

Front 35

What is the MCH, MCV, and MCHC in heriditary spherocytosis patients?

Back 35

-MCV is normal to slightly decreased

-MCH is normal

-MCHC is greater than 36%

Front 36

How is heriditary spherocytosis diagnosed?

Back 36

Osmotic fragility test, splenectomy can correct the patient's anemia and hemolysis in severe cases but the basic membrane defect will remain and spherocytes may still be present.

Front 37

-Caused by a defect in the membrane skeleton

-Most prominent peripherial blood smear finding is an increase in malformed cells (over 25% of population)

-Membrane may fragment under circulation stress and produce RBC fragments

Back 37

Hereditary elliptocytosis

Front 38

True or False: Cells have a normal lifespan when affected with hereditary elliptocytosis

Back 38

True

Front 39

True or False: About 60% of patients with hereditary elliptocytosis will have significant chronic hemolytic anemia

Back 39

False, only about 10%

Front 40

How is hereditary elliptocytosis treated in symptomatic patients, and what are the results?

Back 40

Splenectomy; hemolysis is prevented (most patients show little to no hemolysis in the first place) but elliptocytes will remain

Front 41

-This disorder can be seen in the genetic defect, thalassemia [abnormal hemoglobin production], lead poisoning, and alcoholic cirrhosis.

-The blood cells contain increased sodium and decreased potassium

-The cells are overhydrated

-The anemia is usually mild

-Bilirubin is increased and reticulocytosis is moderate

-The smear shows 10-50% abnormal cells characteristic of this anemia type

Back 41

Hereditary stomatocytosis

Front 42

What is the MCHC and MCV like in hereditary stomatocytosis?

Back 42

MCHC is decreased, MCV is increased

Front 43

-This is a rare hereditary disorder associated with stomatocytosis, spherocytosis, and the deletion of all Rh-Hr determinants on RBC.

-The result is mild anemia (Hbg 11-13 g/dl)

-Reticulocytes are moderately increased.

Back 43

Rh_null Disease

Front 44

Red cells in Rh_null disease are of these types.

Back 44

Spheroidal or stomatocytic

Front 45

The levels of this type of hemoglobin are elevated in Rh null Disease.

Back 45

Hgb F

Front 46

These are types of enzyme defects causing Hemolytic Anemia.

Back 46

G6PD, Pyruvate Kinase, Methemoglobin Reductase

Front 47

-Development of this type of hemolytic anemia is related to drug intake and oxidant stress when patients have this type of defect.

-Red cells cannot compensate for unstable enzymes bc they lack the organelles

-An excess of oxidized glutathione accumulates and forms insoluble complexes with hemoglobin -> Heinz Bodies form

Back 47

G6PD Deficiency

Front 48

These substances can cause anemia in G6PD deficient patients.

Back 48

Primaquine, Chloramphenicol, Quinine, Quinidine, and Fava Beans

Front 49

Describe the lab findings in G6PD Deficient patients. Consider G6PD levels, autohemolysis tests, and bodies that would be present on a stain. Also note what is indicated in the image that may be a clue to diagnosis.

Back 49

-G6PD levels reduced

-Positive autohemolysis test

-Presence of Heinz bodies on a supravital stain (NOT visible on Wright's stain)

-Bite bodies

Front 50

-This enzyme deficiency results in the deficiency in generating ATP.

-Results in water loss and cell shrinkage, shape distortion, and rigidity in membrane

-Premature red cell destruction in the spleen and liver resulting in hematolytic anemia

-Peripherial smear will look normochromic, normocytic with varying degrees of polychromatophilia [ The extra staining is due to too many immature red blood cells (RBCs) called reticulocytes. These cells have a blue colored center.]

-Blood smear looks normal

-Infants in the US are screened for this at birth

Back 50

Pyruvate Kinase (PKU)

Front 51

-In this enzyme deficiency, about 1% of circulating hemoglobin in normal individuals is this type (ferric iron instead of ferrous iron)

-The predominant clinical effect is cyanosis because oxygen cannot effectively be carried to tissues

Back 51

Methemoglobin Reductase Deficiency

Front 52

What are some causes of acquired hemolytic anemia?

Back 52

-Chemicals, drugs, venoms

-Infectious microorganisms

-Immune mechanisms

-Physical agents

-Trauma

*See Slide 55, Anemias powerpoint*

Front 53

True or False: Intravascular hemolysis can result from exposure to environmental agents and persists even after the condition is no longer present.

Back 53

False, conditions usually cease once the threat is gone.

Front 54

Quinine sensitivity can cause this.

Back 54

Hemolytic Uremic Syndrome

Front 55

What are symptoms of Adult Hemolytic Uremic Syndrome?

Back 55

Microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neutropenia, low grade DIC [Disseminated intravascular coagulation]

Front 56

Drugs: What is the preferred target for drug-induced antibodies?

Back 56

Platelets, but white cells, red cells, and other tissues are sometimes affected

Front 57

Chemicals: What effect can chemicals (lead from gasoline, paint, and industrial products) have on blood production?

Back 57

Interfere with ATP production and inhibit heme synthesis

Front 58

Venoms: Venoms from some type of snakes contain this, which can produce intravascular hemolysis and initiate DIC [Disseminated intravascular coagulation]

Back 58

Hemolysins

Front 59

True or False: Infectious Microorganisms (viruses, bacteria, and protozoa) can cause the destruction of red blood cells

Back 59

True

Front 60

This infectious microorganism can rupture red cells.

Back 60

Intraerythrocytic protozoa (malaria)

Front 61

This infectious microorganism releases a hemolytic toxin, in some cases.

Back 61

Clostridium perfringens

Front 62

This infectious microorganism has emerged as a major cause of hemolyric-uremic syndrome.

Back 62

E. coli O157:H7

Front 63

The immune hemolytic anemias are grouped according to the presence of these things.

Back 63

Auto-antibodies, iso-antibodies, and drug related antibodies.

Front 64

This is caused by an altered immune response which results in the production of antibodies against one's own red cells, resulting in hemolysis.

Back 64

Autoimmune hemolytic anemia

Front 65

This type of anemia has been associated with Mycoplasma pneumonia and infectious mononucleosis.

Back 65

Autoimmune Hemolytic Anemia

Front 66

True or False: Autoimmune Hemolytic Anemia can be caused by cold antibodies only.

Back 66

False; can be caused by warm or cold antibodies

Front 67

Usually, warm antibodies are in this class. Hemolysis occurs in this body part.

Back 67

IgG; the spleen *See chart on slide 65 on Anemias ppt*

Front 68

Cold antibodies are this class. Hemolysis usually occurs in this way.

Back 68

IgM; intravascularly

Front 69

This type of anemia usually occurs in newborns because of maternal antibodies crossing the placenta that are directed against antigens on the baby's cells.

Back 69

Isoimmune Hemolytic Anemia

Front 70

Isoimmune Hemolytic Anemia is the most common cause of this type of blood incompatibility reactions between mother and baby.

Back 70

ABO incompatibility

Front 71

This type of anemia may occur following administration of insulin, antihistamines and sulfonamides.

Back 71

Drug Induced Hemolytic Anemia

Front 72

Drug Induced Hemolytic Anemia is this class and results in this event.

Back 72

IgM; hemolysis

Front 73

Hemolysis can occur within 24 hours of this event. In addition to hemolysis, what else occurs?

Back 73

Suffering severe burns; because the red cells become fragile after heat exposure, they form fragments and microspheres. These are removed by the spleen and a rapid drop in circulating red cell volume occurs

Front 74

This is an example of a traumatic of microantiopathic hemolytic anemia. It's a consumptive coagulopathy that involves the deposition of microthombi in the blood cells. These deposits damage circulating red cells.

Back 74

DIC

Front 75

Traumatic injury from repeated impact of the capillary bed can produce red cell damage. What are some examples/causes of this?

Back 75

-March anemia (diagnosed in soldiers after intense marches)

-Long distance runners

-High impact sports

Front 76

How long do normal red cells last in circulation?

Back 76

120 days

Front 77

True or False: As the cell ages, membrane changes occur that cause the spleen to recognize and signal for phagocytic destruction of the cell

Back 77

True

Front 78

Most red cell destruction is [intravascular/extravascular]

Back 78

Extravascular

Front 79

What occurs when red cells are destroyed?

Back 79

-Red cell is reduced back to heme and globin

-Globin is reduced into amino acids and recycled to make new proteins

-Heme is broken into iron + CO +biliverdin

-Iron is recycled into new hemoglobin

-Biliverdin is converted to bilirubin and ultimately excreted in the billary system

*Make a chart later; see slide 73 in first ppt*

Front 80

When the RBC destruction is increased, the formation of this exceeds the liver's ability to conjugate it. This produces elevated levels of the substance in the blood, causing jaundice.

Back 80

Unconjugated billirubin

Front 81

If intravascular hemolysis occurs, this is present in the blood.

Back 81

Free hemoglobin

Front 82

What happens to free hemoglobin in the blood?

Back 82

It is rapidly bound to the carrier protein Haptoglobin; a large complex that cannot pass through the renal glomeruli

Front 83

This is a large complex that cannot pass though the renal glomeruli. It binds to free hemoglobin.

Back 83

Haptoglobin

Front 84

If the amount of intravascular hemoglobin exceeds the amount of haptoglobin present, what may happen?

Back 84

The remaining free hemoglobin may pass through the glomeruli and be excreted in the urine

Front 85

A patient with hemolytic anemia is expected to have these symptoms, as determined by diagnostic tests:

Back 85

-Decreased hemoglobin

-Decreased hematocrit

-Decreased red cell count

-Blood smear showing spherocytes (hallmark abnormality of hemolytic anemias)

Front 86

What is the hallmark abnormality of hemolytic anemia?

Back 86

Spherocytes

Front 87

What are some red cell abnormalities that explicitly described in the chapter?

Back 87

-Acanthrocytes

-Schistocytes

-Polychromasia

-Target Cells

-Early red cells

-Increased reticulocyte count

Front 88

Clinical Chemistry Assays are affected by red cell destruction caused by hemolytic anemia. What would these tests indicate about unconjugated biirubin and serum haptoglobin?

Back 88

Unconjugated Bilirubin - rarely exceed 3-4 mg/dl

Serum Haptoglobin - Decreased levels in the presence of free hemoglobin

Front 89

This is an intravascular hemolytic disorder that is characterized by intermittent sleep-associated blood in the urine.

Back 89

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Front 90

In PNH, these events occur:

Back 90

-Red cell defect that renders the red cells to be very sensitive to the complement

-25% of cases will evolve into or from aplastic anemia

-10% will develop acute myelogenous leukemia

Front 91

Some clinical manifestations of Paroxysmal Nocturnal Hemoglobinuria (PNH) may include:

Back 91

-Chronic Hemolysis

-Thrombosis

-Recurrent Infections

-Tendency toward bone marrow aplasia

Front 92

Describe laboratory findings regarding Paroxysmal Nocturnal Hemoglobinuria (PNH)

Back 92

-Severe anemia HGB - less than 6 g/dl

-Blood smears show hypochromic microcytic cells (result of iron deficiency)

-Sucrose hemolysis and Hamm tests show increased hemolysis

-Hemosiderinuria (excretion of iron from red cell destruction; a classic sign of chronic intravascular hemolysis)

Front 93

What is a classic sign of chronic intravascular hemolysis?

Back 93

Hemosiderinuria (Excretion of iron from red cell destruction) [Brown urine]

Front 94

What are the treatment options for Paroxysmal Nocturnal Hemoglobinuria?

Back 94

Transfusion therapy, antibiotics, anticoagulants

Front 95

Objectives of second anemia ppt:

Back 95

-Describe the clinical signs and symptoms of anemia and common lab tests used to assess anemia

-Describe the characteristics and significance of the following classes of anemia and idenfity the most common examples

*Anemia of blood loss

*Aplastic anemia

*Hypochromic anemias

*Anemias related to iron metabolism

Front 96

Anemia is considered to be present under which condition?

Back 96

When the hemoglobin concentration is below the normal reference range.

Front 97

What are the three causes of anemia?

Back 97

-Blood Loss

-Impaired red cell production

-Accelerated destruction of red cells (Hemolysis)

Front 98

True or False: Anemia often causes many disorders.

Back 98

False, anemia is more often a sign or symptom of an underlying disorder

Front 99

What are the signs and symptoms of anemia a result of?

Back 99

Diminished oxygen delivery to tissues, decreased hemoglobin, lowered blood volume

Front 100

True or False: Anemics will always show symptoms

Back 100

False, if anemia develops slowly, a patient may not show any signs or symptoms until Hgb reaches concentrations as low as 6 g/dl

Note: Normal levels:

* Adult males: 14 to 18 gm/dL
* Adult women: 12 to 16 gm/dL

Front 101

Usual signs and symptoms of anemia include:

Back 101

-Fatigue

-Dizziness

-Weakness

-Headache

-Pallor

-Low blood pressure

-Slight fever

-Edema

Front 102

How is anemia physiologically defined?

Back 102

A condition in which the circulating blood lacks the ability to adequately oxygenate the body tissues

Front 103

Three major laboratory manifestations of anemia are:

Back 103

-Decreased hemoglobin concentration

-Decreased packed cell volume (hematocrit)

-Decreased red cell count

Front 104

Addition to hemoglobin tests, hematocrit tests, and a packed red cell count, these tests are also performed when diagnosing anemia:

Back 104

-Red cell indices (MCV, MCHC, MCH)

-Red cell histogram

-Red cell distribution (RDW)

Front 105

Erythrocyte changes are reported in this way:

Back 105

Semiquantitatively; (Moderate, Marked, Mild) (1+, 2+, 3+, 4+)

Front 106

There are two types of anemias of blood loss. What are they?

Back 106

Anemia from acute blood loss

Anemia from chronic blood loss

Front 107

This type of anemia is associated with traumatic conditions such as accidents or severe injury. It does not occur immediately.

Back 107

Acute blood loss anemia

Front 108

Severe hemmorage of more than ____% of circulating blood volume reduces the total blood volume and produces these problems.

Back 108

20; shock and related cardiovascular problems

Front 109

Severe acute bleeding can be fatal because this may occur. How can it be remedied?

Back 109

Collapse of the circulatory system; immediate expansion of blood volume is required

Front 110

How does the body respond to acute blood loss?

Back 110

It will adjust to the situation by expanding the circulatory volume, which produces the subsequent anemia. Fluid from extravascular spaces enter the blood circulation and dilutes the remaining cells.

Front 111

True or False: Lab findings for patients with acute and chronic bleeding are very similar, sometimes identical.

Back 111

False; they can vary.

Front 112

Describe the difference in lab findings between acute and chronic blood loss anemia.

Back 112

Front 113

What is the first hematologic change that can be seen in an patient suffering from acute blood loss anemia?

Back 113

A fall in platelet count; this is due to platelets being used by the body in an effort to stop the bleeding

NOTE: The platelet levels may rise as the bone marrow responds (within an hour of blood loss)

Front 114

What is the second change seen in acute blood loss anemic patients?

Back 114

An increase in the WBC count and a "shift to the left" (leukocytosis)

NOTE: Hemoglobin and Hematocrit do not decrease immediately, but will decrease as the tissue fluids move into blood circulation (within 48-72 hours)

Front 115

What will an acute blood loss anemic patient's smear look like after 24 hours? MCV? MCH? MCHC?

Back 115

Normochromic and normocytic blood cells, assuming the patient was healthy beforehand. MCV, MCH, and MCHC will also appear normal.

Front 116

How many days does it take reticulocytes to enter circulation after acute blood loss has occurred?

Back 116

3-5 days

Front 117

At what day is the maximum number of reticulocytes present in circulation following acute blood loss?

Back 117

10 days

Front 118

How many days will it take for WBC count to return to normal after acute blood loss?

Back 118

2-4 days

Front 119

How long will it take for the "shift to the left" to no longer be present following acute blood loss?

Back 119

2 weeks

Front 120

This type of anemia is caused as a result of GI tract disorders and/or in women with heavy menstruation or UT abnormalities. The bleeding extends over a period of time, usually months, and occurs in small amounts.

Back 120

Chronic Blood Loss Anemia

Front 121

How is blood volume affected by chronic blood loss? How is the rate of red cell replenishment affected? How is the reticulocyte level affected?

Back 121

Blood volume is unaffected because loss is slow; red cells are replenished at a slower rate than acute loss; reticulocytes may be normal or slightly increased

Front 122

What would the red cells look like in a patient with chronic blood loss anemia?

Back 122

Hypochromic and microcytic

Front 123

CASE STUDY 1: A 38 year old white woman was treated in the emergency department for severe lacerations and possible abdominal injuries sustained in an automobile accident. She was admitted to the hospital for observation and further evaluation. On admission, a complete blood count, urinalysis, and radiograph series were ordered.

LAB DATA:

Hemoglobin: 10.5 g/dl

Hct: 0.34 L/L

RBC: 3.8 * 10^12/L

WBC: 12 * 10^9/L

MCV: 89.6 fL

MCH: 27.6 pg

MCHC: 31%

The Peripherial Blood Smear showed essentially normal RBC morphology and platelet distribution. 48 hours later, the tests were re-ordered. These were the results:

Hct: 0.26 L/L

RBC: 2.9 * 10^12/L

WBC: 15.5 * 10^9/L

The RBC indices were all within normal ranges. Peripherial blood smears indicated that morphology was mostly normal aside from some polychromatophillia. The distribution of platelets was 0.60*10^12/L. The laparotomy determined that the patient had liver and spleen injuries.

1. Why was the patient's hemoglobin and hematocrit normal on admission, but decreased after 48 hours?

2. What is the significance of the patient's increased leukocyte (WBC) and thrombocyte (platelet) count?

3. What is the reason for the polychromatophilia noted on the 48 hour film?

Back 123

1.The body adjusts to severe hemorrhaging by expanding the circulating volume at the expense of the extravascular fluid. The volume adjustment produces a delayed anemia. As the extravascular fluid enters the blood stream, it dilutes the RBCs. The hemoglobin and hematocrit become decreased after 48 hours and 72 hours in some cases.

2. In acute blood loss, the platelets and circulating granulocytes increase within a few hours. Immature WBCs may also be seen. Increased leukocytes and platelets are a normal body's response to stress. The body continually strives to maintain homeostatis.

3. Acute blood loss immediately begins to stimulate a healthy, normal bone marrow. Reticulocytosis becomes apparent within 24 hours and peaks at 7-10 days after severe blod loss. When erythrocyte restoration is completed, reticulocytosis ceases. Reticulocytes are seen as polychromasia or polychromatophilic RBCs when the RBCs are stained with a Wright stain. A supervital stain such as a new methylene blue stain needs to be used to visibly demonstrate reticulocytes in erythrocytes.

DIAGNOSIS: Acute blood loss

Front 124

CASE STUDY 2: A 55 year old white male college professor has been experiencing fatigue and shortness of breath when walking over the past several months. Getting more sleep at night did not help. He reported eating a balanced diet of fruits, vegetables, meat, and dairy products. Upon physical examination, he appeared slightly pale but no other abnormalities. His primary care physician ordered a complete blood count, urinalysis, and fecal occult blood (x3) tests.

LAB FINDINGS:

Hemoglobin 12.5 g/dl

Hematocrit 0.32 L/L

RBC 4.2 * 10^12/L

WBC normal

MCV 42 FL

MCH 29.7 pg

Urinalysis normal

Fetal occult blood POSITIVE

1. What is the most likely cause of this patient's anemia

2. What type of red blood cell morphology would be expected on a peripheral blood smear?

3. What follow-up tests should be conducted?

Back 124

1. The most likely cause of this patient's anemia is chronic blood loss. The source of the bleeding could be the GI tract, in view of the fact that he had a positive test result for fecal blood.

2. Hypochromic, microcytic red blood cells would be expected on the peripheral blood smear.

3. The source of the fecal blood needs to be located. In this case, the patient had a follow-up colonoscopy that revealed a number of non-malignant, bleeding polyps.

Front 125

This is one of a group of disorders known as hypoproliferative disorders that are characterized by a decreased production of blood cells.

Back 125

Aplastic Anemia

Front 126

Other anemias in the category of hypoproliferative disorders, aside from Aplastic Anemia, are caused by deficiencies of:

Back 126

-Erythropoietin

-Iron

-Folic Acid

-Vitamin B12

Front 127

The major form of aplastic anemia is:

Back 127

Idiopathic (of unknown origin)

Front 128

Aside from idiopathic aplastic anemia, what are the two other forms discussed in class?

Back 128

Iatrogenic (drug related) and Constitutional (congenital or genetic predisposition to bone marrow failure)

Front 129

This type of anemia occurs after drug exposure or exposure to cytotoxic chemicals, seen in chemotherapy or radiation therapy.

Back 129

Iatrogenic Aplastic Anemia

Front 130

How do chemicals result in iatrogenic aplastic anemia?

Back 130

Chemicals can injure proliferating and quiescent hematopoietic cells which can lead to the damage of DNA and ultimately cell death.

Front 131

What are some examples of Iatrogenic agents?

Back 131

-Benzene and Benzene derivatives

-Trinitrotolune

-Insecticides and weed killers

-Inorganic arsenic

-Antimetabolites (antifolate compounds and analogues of purines and pyrimidines)

-Antibiotics

Front 132

This type of anemia is characterized by total bone marrow failure with a reduction in circulating levels of red blood cells, white blood cells, and platelets. It is uncommon.

Back 132

Aplastic Anemia

Front 133

What are the two onset types of aplastic anemia?

Back 133

Acute (profound pancytopenia and rapid progresion to death) or insidious (chronic disease course)

Front 134

Signs and symptoms of Aplastic Anemia depend on the degree of deficiencies. They include:

Back 134

-Bleeding from thrombocytopenia

-Infection from neutropenia

-Anemia (obviously? huh.)

Front 135

True or False: Sphenomegaly and lymphadeopathy are present in patients with aplastic anemia.

Back 135

False; they are absent

Front 136

What are aplastic anemia survivors predisposed to?

Back 136

Paroxysmal nocturnal hemoglobinuria (PNH), Myelodysplasia, and acute myelogenous leukemia

Front 137

Describe the laboratory findings of Aplastic Anemia.

Back 137

-Caused by damage to the hematopoietic tissue of bone marrow that results in deficient blood cell production

-Pancytopenia - all cell lines are affected

***IF ONLY ONE CELL LINE IS INVOLVED, it is usually the red cell line***

-If two or more cell lines are affected, it's referred to as severe aplastic anemia

-Red cells: normochromic and normocytic [in some cases, there may be varying degrees of anisocytosis and poikilocytosis or macrocytosis

-Serum iron is increased [this is a valuable early sign of erythroid hypoplasia and reflects decreased plasma iron turnover]

-Bone Marrow exam shows very few early erythroid and myeloid cells, few to none megakaryocytes

Front 138

True or False: Aplastic Anemia is a poor prognosis, with a high mortality rate.

Back 138

True

Front 139

What are some complications of aplastic anemia?

Back 139

-Infections

-Bleeding

-Problems from iron overload and repeated transfusions

Front 140

What are some modern treatment options for aplastic anemia that have improved its mortality rate?

Back 140

Immunosuppressant therapy and bone marrow transplant

Front 141

This is a congenital form of aplastic anemia.

Back 141

Fanconi's Anemia

Front 142

What are the clinical signs of Fanconi's Anemia?

Back 142

-Low birth weight

-Skin hyperpigmentation

-Short stature

Other manifestations:

-Skeletal disorders

-Renal malformations

-Microcephaly

-Hypogonadism

-Mental retardation

-Strabismus

Front 143

Describe the lab findings of Fanconi's Anemia

Back 143

-Progressive pancytopenia usually apparent by age 5

-Hemoglobin concentration 5-6 g/dl at diagnosis

Front 144

What is the treatment for Fanconi's Anemia?

Back 144

Bone marrow transplant or cord blood treatment

Front 145

This is the hypoproliferation of the red cell line without a corresponding decrease in other cell lines.

Back 145

Pure red cell aplasia

Front 146

Some causes of red cell aplasia are:

Back 146

-Congenital - Diamond-Blackfan syndrome

-Acquired chronic - Idiopathic, associated with thymoma and lymphoma

-Acute (transient) - parvovirus, other infections, drugs, riboflavin deficiency

Front 147

This is a rare congenital form of red cell aplasia, resulting from a defective stem cell, probably the committed erythroid stem cell. It is characterized by a slowly progressive refractory anemia with no concurrent leukopenia or thrombocytopenia

Back 147

Diamond-Blackfan Syndrome

Front 148

This is the deficiency of red blood cells that does not readily yield to treatment

Back 148

Refractory anemia

Front 149

Describe the lab results for Diamond-Blackfan syndrome

Back 149

-Occurs in early infancy

-Severe normochromic, slightly macrocytic anemia

-Bone marrow shows reduction in erythroid precursors but normal granulocytic and megakaryocytic lines

-Fetal Hgb is elevated (5-25%)

-Most patients respond to steroid treatments

Front 150

This is one of the most commonly encountered deficiency-related anemias.

Back 150

Iron deficiency anemia

Front 151

What are the four conditions that can result in iron deficiency anemia?

Back 151

-Nutritional deficiency

-Faulty or incomplete iron absorption

-Increased demand for iron that is not met

-Excessive loss of iron

Front 152

Dietary iron has two sources. What are they?

Back 152

Non-heme iron and heme iron

Front 153

What are the two forms that iron is stored?

Back 153

Ferritin and hemosiderin

Front 154

What are the clinical signs and symptoms of iron deficiency in children?

Back 154

Psychomotor and mental impairment in the first two years of life and Pica

Front 155

Describe the lab findings in iron deficient anemia.

Back 155

-Decreased Hbg and Hct

-Red cell counts are normal initially, but will decrease as the iron deficient state continues

-Decreased MCV, MCH, MCHC

-Hypochromic, microcytic cells

-Platelets are normal

-Leukocytes are normal

-Reticulocytes are decreased or normal

-Bone marrow exam reveals marked decrease in sustainable iron

Front 156

Describe the chemistry-based lab findings for iron deficiency anemia.

Back 156

-Serum iron: significantly decreased

-Total iron binding capacity: increased

-Percent saturation: Significantly decreased

-Serum ferretin: decreased***

***Currently accepted lab test for iron deficiency diagnosis; significantly decreased levels is highly specific for iron deficiency

Front 157

True or False: Any inflammatory condition that lasts for at least two weeks can produce anemia.

Back 157

False; lasts for 1-2 months

Front 158

Anemia of inflammation can result from:

Back 158

-Decreased release of iron from the RE system -> decreased iron supply to bone marrow

-Inappropriately decreased erythropoietin production

-Suppression of erythropoiesis by cytokines (from the inflammatory response)

Front 159

Anemia associated with malignancy can be caused by:

Back 159

-Decreased red cell production because of bone marrow infiltrated by a tumor

-Release of cytokines by microphages in response to a tumor

-Increased red cell destruction due to hemolytic anemia

-Acute and chronic blood loss

-Toxic effects of treatment

Front 160

Describe the lab results for anemia of inflammation.

Back 160

-Mild hypoprolific anemia with hematocrit around 30%

-Normochromic, normocytic anemia, but sometimes hypochromic, microcytic

-Bone marrow does not show erythroid hyperplastia or reticulocytosis

-Normal or increased iron stores in bone marrow

Front 161

Describe the lab results for patients with malignancies.

Back 161

-In patients with malignancies, immature red and white cells can be seen

-Abnormal red cell morphology

-Low serum iron

-Total iron binding capacity is decreased

-Transferrin levels are decreased

Front 162

Describe treatment options for patients with anemia of inflammation.

Back 162

-Treatment of the underlying cause

-If severe - blood transfusion

-Iron therapy is NOT effective bc the patient is not utilizing iron effectively

-Another option: erythropoeitin injections

Front 163

This type of anemia is associated with mitochondrial iron loading in the marrow erythroid precursors (ringed sideroblasts) and ineffective erythropoeisis.

The body has adequate iron, but it is unable to incorporate it into hemoglobin. Iron enters the developing red cell, but then accumulates in the mitochondria of the normoblast.

-There is a decrease in the enzyme delta ALA synthetase.

Back 163

Sideroblastic anemia

Front 164

What are some causes of sideroblastic anemia?

Back 164

-Congenital defects

-Acquired defects

-Malignant marrow disorders

-Drugs

-Toxins (alcohol or chronic lead poisoning)

Front 165

How is sideroblastic anemia diagnosed?

Back 165

-Variable red cell indices with microcytic hypochromic red cell picture

-Increased serum iron and ferritin

-Characteristic ringed sideroblast in bone marrow when stained for iron

Front 166

Describe the lab findings of sideroblastic anemia.

Back 166

-Ringed sideroblast seen in bone marrow with a Prussian Blue stain

-Increased erythtopoietic activity in bone marrow

-Bone marrow will appear hypercellular, but the number of circulating reticulocytes is not elevated

-Mature red cells are hypochromic with normocytic and microcytic cells (dimorphic population)

-Target cells, basophilic stippling, dimorphic red cells are seen

-10-40% of the nucleated red cells in the bone marrow are ringed sideroblasts

-Leukocytes and platelets are usually normal

-Iron and serum ferritin levels are increased

Front 167

This is a hereditary disorder of metabolism that produces inappropriately increased GI absorption of iron. It causes a progressive iron overload and excessive accumulation of iron in various organs.

Back 167

Hereditary hemochromatosis

Front 168

Describe the lab findings of hemochromatosis

Back 168

-Serum iron and total iron binding are increased

-Ferritin levels are increased

Front 169

Describe the treatment options for hemochromatosis.

Back 169

Therapeutic phlebotomy or iron chelation therapy

Front 170

Objectives of Hematoglobinpathies Powerpoint:

Back 170

-Describe hemoglobin defects and the effects of hemoglobinpathies that have a normal red cell function

-Correlate lab data to the disease state

-Describe lab findings in thalassemias

Front 171

What are the two most common hemoglobinpathies?

Back 171

Sickle cell anemia/trait and thalassemiaW

Front 172

What do most hemoglobinpathies arise from?

Back 172

Single amino acid substitutions

Front 173

What are the two ways in which these diseases can be inherited and how do they present in the child?

Back 173

-Autosomal dominant (will produce hemolytic disease in the heterozygous state)

-Autosomal resessive (needs to be in the homozygous state to produce disease)

Front 174

What is the distinction between disease state and trait condition in hemoglobinopathies?

Back 174

Homozygous occurence of the gene (s/s) or possession of a heterozygous dominant gene that produces a hemolytic condition = DISEASE

Heterozygous and normally asymptomatic state (S/s) = TRAIT

In sickle cell anemia, the trait must be inherited from both parents in order to have the disease

Front 175

What are the percentages for normal adult hemoglobin? (A, A1, A2, F)

Back 175

Hb A - 95-98%

Hb A1 - 3-6%

Hb A2 - 2-3%

Hb F - <1%

Front 176

What is sickle cell disease characterized by?

Back 176

-Production of Hb S

-Anemia

-Acute and chronic tissue damage secondary to the blockage of blood flow due to abnormally shaped cells

Front 177

What are common variants of sickle cell disease?

Back 177

-Hemoglobin SC disease

-Beta-ThalassemiaT

Front 178

True or False: Every state in the US screens the blood of newborns for sickle cell disease

Back 178

True

Front 179

This is the cause of sickling on red blood cells.

Back 179

-When Hb S is deoxygenated, it becomes polymerized and produces sickling

Front 180

What is sickling promoted by?

Back 180

-Extremely reduced oxygen conditions (low oxygen tension)

-Increased acidity in the blood (low pH)

-Inreased 2,3-DPG

-High cellular concentrations of hemoglobins

-Loss of cell water

-Hemoglobin C

Front 181

True or False: When sickled cells receive oxygen, they return to the normal shape

Back 181

True

Front 182

Repeated cycles of sickling and unsickling leads to permanent damage of the red cell. What are some side effects of this?

Back 182

Hemolysis, anemia, necrosis of body tissues due to lack of oxygen

Front 183

Describe the laboratory results for sickle cell anemia.

Back 183

-Hgb decreased

-Hct decreased

-Red cell count decreased

-Persistent increase in wbc

-Red cell morphology includes anisocytosis, poikilocytosis and hypochromia

-Target cells, microcytes, polyhromatophilia, basophilic stippling

-Sickle cells during crisis

-Reticulocytes may be increased; increased MCV

-Increased unconjugated bilirubin

-Increased methamalbumin

-Haptoglobin decreased

-Increased LDH, AST

-Increased urine urobilinogen

Front 184

List other diagnostic tests to determine if a patient has sickle cell anemia.

Back 184

-Sickle cell screening tests

-Hemoglobin electrophoreisis

-Alkali denaturation

-Acid elution tests

Front 185

Describe the results of the hemoglobin electrophoresis test for a sickle cell disease patient.

Back 185

-Hemoglobin Electrophoresis:

*80-95% Hgb S

*0-20% Hgb F

*Normal small amt of Hgb A2

Front 186

How can newborns be screened for sickle cell disease?

Back 186

-Specimen obtained by heel stick

-Cord blood

-Electrophoresis at alkaline pH using cellulose acetate

-Confirmation by electrophoresis at acid pH on citrate agar

Front 187

This type of sickle cell screening is used only on adults and children, not newborns.

Back 187

Metabisulfite sickle cell screening

Front 188

Describe methods to manage sickle cell disease.

Back 188

-Early detection and treatment of infections

-Oral folate supplementation

-Regular vaccines and check-ups

-Treatment of pain crisis using:

*Hydration

*Analgesics

*Oxygenation

*Transfusion therapy

*Hydroxyurea (stimulates Hb F production)

Front 189

This is a disorder in which the patient inherits a sickle gene from one parent and a gene for this disorder from the other parent. It results in severe hemolytic anemia.

Back 189

Sickle-Beta Thalassemia

Front 190

Describe blood smear results for Sickle-Beta Thalassemia.

Back 190

-Hypochromic, microcytic red cells with polychromatophilia

-Target cells, stippling - rarely sickle cells

-60-90% is Hb S

-Splenectomy may be beneficial

Front 191

In this disease, patients only have HbS and HbC. Hgb A is absent, Hgb F is normal or increased. Mild anemia occurs in only 10% of patients and sickle cells are rarely seen. 50% of the cells are target cells and the spleen remains functional. Mild to moderate hemolysis. Target cells and plump sickle forms are seen on smears.

Back 191

Sickle C disease

Front 192

This condition occurs when the patient inherits one HbS gene and one normal gene. With this condition, they have immunity to P. falciparum malaria. 35% of the cells contain HgbS.

Back 192

Sickle cell trait

Front 193

Thalassemia symptoms are caused by an abnormality in:

Back 193

The rate of synthesis of the globin chains, characterized by the absence or decrease in the synthesis of one of the two constituent globin subunits of the normal hemoglobin

Front 194

In this type of thalassemia, there is decreased synthesis of a certain type of alpha globulin. This results in the accelerated red cell destruction because of the formation of insoluble Hb H (excess beta chains) in red cells.

Back 194

Alpha thalassemia

Front 195

True or False: Beta thalassemia is more severe than alpha thalassemia.

Back 195

True; there is decreased beta globulin synthesis and alpha chains will precipitate, causing more problems with the beta chains

Front 196

Patents with Beta Thalassemia produce lots of this type of hemoglobin

Back 196

Hgb F

Front 197

Describe the laboratory findings for Beta Thalassemia.

Back 197

-Decreased hemoglobin

-Decreased hematocrit

-Decreased red cell count

Smears will show:

-Anisocytosis

-Poikilocytosis

-Hypochromia

-Target cells

-Polychromatophilia

-Nucleated red cells

-Microcytic

-Hypochromic

-MCV - Reduced

-MCH - reduced

-MCHC - reduced

-RDW increased due to anisocytosis

-Reticulocytes are increased

-Bilirubin and iron are increased

-Ferritin is increased

-Hemoglobin electrophoresis shows increased Hgb F and decreased Hgb A

Front 198

How can Beta Thalassemia be treated?

Back 198

-Regular blood transfusions, which may cause iron accumulation problems

-Chelation therapy

Front 199

In this situation, only one abnormal gene is passed to the offspring. Patients can produce an adequate amount of alpha chains for hemoglobin synthesis.

Back 199

Silent carrier state of alpha thalassemia

Front 200

What are conditions for alpha thalassemia trait?

Back 200

-Two missing genes

-Imbalance in production, Beta chains accumulate

Front 201

What occurs when a patient has Hemoglobin H disease?

Back 201

-Three gene deletions are present

-Hb H is formed (4 beta chains)

-Hemoglobin is nstable - precipitates in the red cells

-Decreased cell life span due to membrane damage

-Chronic, moderately severe anemia

-Reticulocytes are increased, indices decreased

-Hgb electrophoresis shows HbH, small amount of Hb Bart's with no HbA

Front 202

What are the symptoms of hydrops fetalis?

Back 202

-Four gene deletions

-Total lack of alpha chains

-Incompatible with life

-Only Hgb produced is Hgb Barts (4 y chains)

Front 203

Describe the situation in the body when a patient is infected with Hemoglobin C disease.

Back 203

-Hb C differs from Hb A in one amino acid

-When Hb C is deoxygenated, it tends to form intracellular crystals

-Red cells are normochromic and normocytic

-More than 50% of cells are target cells

-Mild, chronic hemolytic anemia with splenomegaly

Front 204

What is the formula for calculating MCV? What is the normal value? What will cells look like if the value is normal, high, or low?

Back 204

MCV

Formula: Hct(%) * 10 / RBC Count = fL

Normal Range: 80-96 fL

Normal value: Normocytic

Low value: Microcytic

High value: Macrocytic

Front 205

What is the formula for calculating MCH? What is the normal value? What will cells look like if the value is normal, high, or low?

Back 205

MCH

Formula: Hgb (g/dl) * 10/ RBC Count = pg

Normal range: 27-32 pg

Normal value: Normocytic

Low value: Microcytic

High value: Macrocytic

Front 206

What is the formula for calculating MCHC? What is the normal value? What will cells look like if the value is normal, high, or low?

Back 206

MCHC

Formula: Hgb(g/dl) * 100 / Hct(%) = %

Normal Range: 32-36%

Normal value: Normochromic

Low value: Hypochromic

High value: Hyperchromic

Front 207

What is the general rule for counting blood cells?

Back 207

Count cells touching the top and left of the square to prevent counting the same cells twice.