The Microcytic Anemias

Front 1

when does an anemia occur?

Back 1

when RBCs are no longer able to supply O2 to the body tissues.

Front 2

how are anemias classified?

Back 2

.physiology (symptoms & bone marrow response)
.morphology (RBC indices=MCV, mchc (anemia classification) <6 microcytic.

Front 3

normal MCV (mean corpuscular volume)

Back 3

80-100 fL

Front 4

normal MCH (mean corpuscular hemoglobin)

Back 4

27-31 pg

Front 5

normal MCHC (mean corpuscular hemoglobin content)

Back 5

32-36%

Front 6

what happens when a microcytic, hypochromic anemia develops?

Back 6

MCV <80 fL and MCHC <32%

Front 7

what are RBCs termed when MCH and MCHC are lowered and what do they look like?

Back 7

microcytic, hypochromic and appear as small cells, deficient in hemoglobin.

Front 8

what are the types of microcytic anemias?

Back 8

.iron deficiency anemia (IDA)
.sideroblastic anemias (acquired and inherited)
.thalassemias
.some anemias of inflammation or chronic disease transcend into IDA.

Front 9

how much iron should men and infants absorb a day?

Back 9

1mg/day

Front 10

how much iron should premenopausal women absorb a day?

Back 10

0.2-2.0mg/day

Front 11

how much iron should children absorb a day?

Back 11

0.5mg/day

Front 12

what happens to iron when it's ingested?

Back 12

absorbed in the GI tract and transported in the circulation.

Front 13

what main part of the GI tract is involved in the absorption of iron? and how much does it absorb?

Back 13

duodenum and jejunum of the small intestine. about 10% of ingested iron.

Front 14

is the absorption rate static?

Back 14

no, it decreases or increases relative to iron stores and the body's needs.

Front 15

when iron is absorbed into the body what are the steps to get it to the bone marrow?

Back 15

.stomach acid converts fe3+ (ferric) to fe2+ (ferrous)
.fe3+ are transported to bone marrow by transferrin

Front 16

what is transferrin?

Back 16

A plasma protein formed in the liver that assists iron delivery erythroblasts in the bone marrow, transport vehicle.

Front 17

How does transferrin work?

Back 17

Transferrin receptors on the pronormoblast bind iron so that iron molecules can immediately begin incorporation into the heme molecule during erythropoiesis.

Front 18

What is the ability of transferrin receptor binding iron influenced by?

Back 18

Iron being delivered; the pH of the body; and on the molecular level, the influence of an iron regulatory factor, ferritin repressor protein.

Front 19

What are the primary storage forms of iron?

Back 19

Ferritin and hemosiderin

Front 20

Where are ferritin and hemosiderin located?

Back 20

They are harbored in the liver, spleen, bone marrow, and skeletal muscle.

Front 21

What iron store can be measured in plasma?

Back 21

ferritin

Front 22

What iron store can be identified in the urine or stained through bone marrow slides?

Back 22

Hemosiderin

Front 23

In men, how many grams in iron stores are generally of that of body iron?

Back 23

1.0 to 1.4 grams of body iron.

Front 24

In women, how many iron stores in grams are generally of that of body iron?

Back 24

0.2 to 0.4 grams

Front 25

How long would 1 gram of stores in men last?

Back 25

3 to 4 years before iron depletion occurs.

Front 26

In most cases iron deficiency relates directly to what?

Back 26

External blood loss especially menorrhagia or slow GI bleed.

Front 27

Where are the heme and amino acids recycled to?

Back 27

heme is returned to the bone marrow storage pool, and the amino acids of the globin chain are returned to the amino acid storage pool.

Front 28

What percentage of recycled iron is approximately used for red blood cell production?

Back 28

95% for adults 70% for infants

Front 29

Is iron sources during the early years of development important?

Back 29

Yes

Front 30

What can IDA be resulted from?

Back 30

blood loss or inadequate iron intake. By a disease process or conditions that deplete iron stores, such as GI bleed or pregnancy.

Front 31

And IDA the complete blood count is characterized by what?

Back 31

Decreased red blood cell count, hemoglobin, hematocrit, MCV, and MCHC and increased red blood cell distribution width (RDW).

Front 32

What decreases at every stage of iron deficiency anemia?

Back 32

Serum ferritin

Front 33

What may a patient with IDA present?

Back 33

Fatigue, pallor, vertigo, dyspnea, cold intolerance, lethargy, pica (craving for unusual things ex. dirt), cheilosis (inflammation around the lips), and koilonychia (spooning of the nails).

Front 34

What factors affect iron absorption?

Back 34

.the health of the gastric mucosa
.the current iron stores
.the erythropoietic need
.the amount of iron ingested.

Front 35

What is serum iron?

Back 35

Total iron in serum

Front 36

What is serum ferritin?

Back 36

Acute phase reactant, and one of the most sensitive indicators of iron stores.

Front 37

What is transferrin?

Back 37

Iron form during transport

Front 38

What is total iron binding capacity(TIBC)?

Back 38

Availability for binding to transferrin.

Front 39

What is transferrin saturation?

Back 39

% (serum iron/TIBC) x 100

Front 40

What is the normal reference ranges for serum iron?

Back 40

50-160 microgram/dL

Front 41

What is the normal reference range for serum ferritin of males and females?

Back 41

males: 15-400 micrograms/ml
females: 10-106 micrograms/ml

Front 42

What is the normal reference range for TIBC?

Back 42

250-400 micrograms/dl

Front 43

What is the normal reference range for transferrin saturation?

Back 43

20-55%

Front 44

What percent is considered iron overload?

Back 44

>55%

Front 45

What are treatments of IDA?

Back 45

.oral iron
.Forms of ferrous sulfate, ferrous gluconate, and ferrous fumerate at 325 milligrams

Front 46

Who are the owner of all patients of IDA?

Back 46

Infants, pregnant women, young children, and elderly individuals.

Front 47

If iron deficiency is suspected what must be analyzed?

Back 47

Red blood cells status and iron status

Front 48

what tests assess a patients iron status?

Back 48

serum iron, serum ferrin, TIBC, and transferrin saturation.

Front 49

a patient with IDA has a CBC of what? and iron profile of what?

Back 49

CBC: decreased RBC count, Hgb, hematocrit, MCV (microcytic), MCHC (hypochromic), target cells and ellipotocytes
Iron Profile: decreased serum iron, ferritin (iron stores), and iron saturation and increase of TIBC.

Front 50

what is a differential diagnosis?

Back 50

establish if there is an iron deficiency process; a physician examines a group of laboratory values and symptoms and tries to correlate them to a particular physiology.

Front 51

what does a patient anemia of chronic disease show?

Back 51

borderline low RBC count, hemoglobin, and hematocrit; slightly low MCV; normal MCHC; low serum iron; normal/increased serum ferritin; decreased serum TIBC.

Front 52

what happens in a patient with anemia of inflammation?

Back 52

iron is blocked from reaching erythroid precursors because of impaired release from macrophages, there is impaired EPO production, and the pronormoblasts are not responsive to EPO from patients with chronic disease.

Front 53

what regulates iron transit, where is it produced and what is it greatly influenced by?

Back 53

hepcidin; liver; iron overload and anemia inflammation.
hepcidin increases as iron levels increase.

Front 54

what are sideroblastic anemias related to?

Back 54

mitochondrial overload.
either inherited (enzyme deficiency) or acquired(alcoholism, lead poisoning, or chloroamphenicol use).

Front 55

what are ringed sideroblasts?

Back 55

iron accumulation leading to the presence of iron deposits in the RBC precursors in the bone marrow.

Front 56

what happens if the sideroblastic anemia is inherited?

Back 56

it can be congenital sex-linked or autosomal recessive condition.

Front 57

what leads to the sideroblastic anemia?

Back 57

a mutation in the delta amino levulinic acid leads to this linked condition.

Front 58

What does a peripheral smear of sideroblastic anemia show?

Back 58

It shows a microcytic process, with the dimorphism (some microcytes and some normal cells, some hypochromic and some normochromic) and the presence of pappenheimer bodies, RBCs with precipitated iron inclusions that look like grape clusters in the periphery of the RBC.

Front 59

What does the iron profile reveal of a sideroblastic anemia?

Back 59

Increased serum ferritin and increased serum iron.

Front 60

What is the most common genetic disorder in a person with European ancestry and a major disorder? And how many people in the United States are affected?

Back 60

Hereditary hemochromatosis (HH) more than 1 million people are affected in the United States.

Front 61

What is HH and how is it inherited?

Back 61

It is an autosomal recessive disorder carried on chromosome 6 that is closely linked to HLA-A3. It may be inherited homozygously or heterozygously with homozygotes more prone to iron overload.

Front 62

When does HH begin to load iron excessively

Back 62

From a young age and continued iron loading with every decade.

Front 63

Is the diagnosis of HH made accidentally?

Back 63

Yes

Front 64

What is happening with iron when a patient is diagnosed with HH?

Back 64

Iron absorption and storage becomes unbalanced because of the inheritance of HFE, an abnormal gene that regulates the amount of iron absorbed from the diet.

Front 65

What are the two mutations of HH?

Back 65

CY82Y and H63D

Front 66

Does the normal product of the genes from HH bind to the transferrin receptor in the normal iron delivery process?

Back 66

no

Front 67

What is the results of the faulty mechanism when the normal product is not binding to the transferrin receptor?

Back 67

Iron is constantly loaded into the storage sites and leads to multiorgan damage and symptoms over decades.

Front 68

What ions statuses are seen in patients with HH?

Back 68

Patients with HH have serum iron, serum ferritin, and transferrin saturation elevation, where as TIBC and transferrin fall in the normal reference range.

Front 69

What is indicative of HH with serum ferritin and transferrin saturation levels?

Back 69

.serum ferritin levels >150 micrograms/L
.transferrin saturation levels >45%

Front 70

What kind of testing would be appropriate for individuals to establish if they possess the C282Y and H63D mutation? And what percent of patients have these mutations?

Back 70

Genetic testing; 80-95%

Front 71

What does untreated HH lead to?

Back 71

Can be fatal and advanced iron overload frequently leads to liver cancer.

Front 72

What treatment is the choice for individuals with a diagnosis of HH?

Back 72

Aggressive therapeutic phelobotomy, or bloodletting.

Front 73

What is the goal of the aggressive therapeutic phelobotomy?

Back 73

The goal is to reduce the serum ferritin level to less than 10 micrograms per deciliter and keep the patients hematocrit at around 35%.

Front 74

Does iron overload cause a significant amount of diabetes?

Back 74

Yes

Front 75

can deferrioxamine (Desferal), an iron-chelating agent, be used for patients who cannot tolerate the phelbotomy treatment of HH?

Back 75

yes

Front 76

Is HH known as the silent killer?

Back 76

Yes

Front 77

How many Americans carry the gene for thalassemia?

Back 77

More than 2 million Americans

Front 78

A patient with a microcytic process and normal iron status may possibly have what condition?

Back 78

thalassemic condition

Front 79

Is there a cure for thalassemia?

Back 79

No

Front 80

Does thalassemia have anything to do with iron?

Back 80

No

Front 81

what are the two major types of thalassemias?

Back 81

Alpha thalassemia and beta thalassemia

Front 82

What does the alpha thalassemia and beta thalassemia result from?

Back 82

The alpha thalassemia results from gene deletions. while the beta thalassemia revolves around the inheritance of a defective gene, either from one parent or from both parents.

Front 83

What is the difference between B0 gene mutation and B+ gene mutation?

Back 83

B0 individuals have a complete lack of synthesis on the beta chain, and B+ individuals have a limited amount on the beta chain synthesized.

Front 84

What do beta chain defects result from?

Back 84

Faulty transcription of messenger RNA.

Front 85

What population does alpha thalassemias arise highly in?

Back 85

asians (highly) and also in Saudi Arabian and Filipino.

Front 86

What is the critical building block for construction of all normal adult physiologic hemoglobins?

Back 86

Alpha chains

Front 87

What is the most critical condition of alpha thalassemia?

Back 87

Barts hydrops fetalis

Front 88

How is Bart's hydrops fetalis characterized?

Back 88

It has a total absence of alpha chain synthesis. No hemoglobin A is formed only hemoglobin barts which is a high oxygen affinity hemoglobin.

Front 89

What does Bart s hydrops fetalis leads to when the anemia develops severely?

Back 89

stillbirth or spontaneous abortion

Front 90

What is the second most of the air condition of alpha thalassemias?

Back 90

Hemoglobin H disease.

Front 91

How is hemoglobin H characterized?

Back 91

One functional alpha gene; the other three genes are deleted. Little hemoglobin A is produced; instead, a new hemoglobin H is formed, which is also a fairly unstable tetramer and represents 5-40% on alkaline electrophooresis.

Front 92

what are observed in the peripheral smear of Hgb H disease?

Back 92

microcytosis and hypochromia are observed in the peripheral smear with RBC fragments.

Front 93

what stain is used when an inclusion looks like a pitted golf ball?

Back 93

brilliant cresyl blue or crystal violet stain.

Front 94

individuals with Hgb H have what kind of lifelong abnormalities?

Back 94

lifelong anemias with variable splenomegaly and bone changes.

Front 95

what are the two less severe conditions of alpha thalasemia?

Back 95

alpha thalassemia trait (2 gene deletion state)
silent carrier (1 gene deletion state)

Front 96

what is alpha thalassemia trait?

Back 96

possess 2 viable Hgb A genes and may have only mild anemia with many microcytic, hypochromic cells. some Hgb Bart's formed. presence of elliptocytes and target cells in peripheral .

Front 97

what is alpha thalassemia silent carrier?

Back 97

hematologically normal or slightly microcytic, and the pat smears ient may be unaware of his or her alpha gene status. presence of elliptocytes and target cells in peripheral .

Front 98

how is Hgb H diagnosed?

Back 98

CBC shows slightly elevated RBC combined with extremely low MCV (less than 60fL) and RDW are extremely elevated owing to the misshapen RBC s and fragments compared with the more homogeneous microcytic, hypochromic population seen in IDA.

Front 99

What is the treatment for hemoglobin H disease?

Back 99

Transfusions are given only if necessary. Iron deficiency must be eliminated as a reason for the microcytic indices so that the patient is not given iron unnecessarily.

Front 100

What is an inherited blood disorder that affects millions of individuals worldwide and more than two million individuals are carriers?

Back 100

Beta thalassemia major

Front 101

Does beta thalassemia major often lead in disease?

Back 101

Yes

Front 102

What happens in a person that has beta thalassemia major?

Back 102

Embed a fallacy nyan major, little or no beta chain is synthesized; consequently, no or very little hemoglobin A is synthesized.

Front 103

How serious is beta thalassemia major?

Back 103

It is serious enough that it threatens genetic blood disorder, affecting multiple organs, quality of life, and longevity.

Front 104

When does beta thalassemia major show up?

Back 104

Most infants born with thalassemia major are not ill for the first 6 months because fetal hemoglobin is the majority hemoglobin at birth.

Front 105

What are the normal sequence of events in beta thalassemia major?

Back 105

Gamma chains are silenced, and beta change increase, forming hemoglobin A between three and six months.

Front 106

What happens with children ages 2 to 4 who have beta thalassemia major?

Back 106

Most young children begin to show a failure to thrive, irritability, enlarged spleen, symptoms of anemia, jaundice, and transfusion requirements.

Front 107

What is shown in a patient living with thalassemia major?

Back 107

The patient's peripheral smear shows a severe microcytic, hypochromic process with a high number of nucleated red blood cells, marked polychromasia, and a high degree of red blood cell morphology.

Front 108

What is true with patients that have beta thalassemia major and problems overloading iron?

Back 108

Patients with beta thalassemia major absorb more iron through diet because of increased erythropoiesis, and they accumulate iron because they take in an additional 200 milligrams of iron with each transfusion of packed red blood cells.

Front 109

How is a patient with thalassemia major treated when they have a low transfusion?

Back 109

A low transfusion protocol treats the patients symptomatically, administering transfusion when symptoms warrant.

Front 110

How is the patient with kelsey me a major treated when I have a high transfusion?

Back 110

A high transfusion protocol aims to keep the patient's hemoglobin levels close to 10 grams per deciliter, and the patient is transfused every 2 to 5 weeks.

Front 111

Which transfusion type give be patient a better outlook?

Back 111

A high transfusion protocol gives the patient the best hope for a normal quality of life by increasing his or her hemoglobin and providing better bone quality, better growth, less iron, and near normal spleen size.

Front 112

Does iron overload pose significant risks to cardiac function and does it lead to hepatic an endocrine complications?

Back 112

Yes

Front 113

What is recommended when the serum ferritin level has reached about 1000 micrograms per liter in talasemia major ?

Back 113

Iron chelation

Front 114

When does thalassemia major begin to be difficult to maintain?

Back 114

As the patient moves from childhood to adolescence and becomes less willing to be hooked up to the infusion pump.

Front 115

What is the leading cause of death in patients with thalassemia major?

Back 115

Cardiac complication

Front 116

What therapeutic modalities are available for severely thalassemic patients?

Back 116

Bone marrow transplantation and stem cell transplantation

Front 117

When should bone marrow transplant be considered

Back 117

It should be considered early before the patient develops too many complications of thalassemia.

Front 118

When does thalassemia intermedia develop?

Back 118

problems develop later in life than patients with a major they may not need transfusions

Front 119

Does dallas CMIA intermedia mimic IDA?

Back 119

yes

Front 120

How do you know that thalassemia intermedia from IDA?

Back 120

Increase red blood cells are significant in the condition because it represents that the bone marrow is compensating for having only one half the complement of the beta chains.

Front 121

Are many patients with beta thalassemia minor put on our protocols that offered no therapeutic value?

Back 121

Yes

Front 122

Is beta thalassemia intermedia versatile?

Back 122

Yes