Hematology Exam 3 Flashcards
1
Q
What is one of the largest organs in the body?
A
Bone marrow
2
Q
What percentage of our body weight is bone marrow?
A
4%
3
Q
Where is bone marrow found in infants?
A
All bones
4
Q
Where is bone marrow found in adults?
A
Flat bones
5
Q
Where are RBCs located in bone marrow?
A
Inside the sinus around a macrophage
6
Q
Where are megakaryocytes located in bone marrow?
A
Near the sinus wall
7
Q
Ratio of fat to tissue in normal bone marrow
A
50:50
8
Q
Job of macrophages in bone marrow
A
To incorporate iron into the red cells
9
Q
What forms the foundation or support of bone marrow?
A
Meshwork of stromal cells
10
Q
Cells unique to bone marrow
A
Osteoclasts - bone destroying/breakdown
Osteoblasts - bone forming
11
Q
Name the cells
A
Osteoblasts
12
Q
Name the cells
A
Osteoclasts
13
Q
What is circled? (BM)
A
Spicules in bone marrow
14
Q
What does seeing spicules tell you?
A
You have a good aspirate
15
Q
Where does the core biopsy go in the lab?
A
Histology
16
Q
Lifespan of RBCs
A
120 days
17
Q
Lifespan of WBCs
A
anywhere from 7 hours to 20 days depending on the type of WBC
18
Q
Function of bone marrow
A
Supplies mature cells for circulation in steady state or for increased demand
19
Q
What maintains the self-renewal of bone marrow?
A
Pluripotential stem cells
20
Q
What are some examples of stimuli received to create cells in the bone marrow?
A
- Thrombopoietin
- Erythropoietin
- Colony stimulating factors
- Interleukins
21
Q
What is produced by stromal cells, fibroblasts, endothelial cells, and macrophages?
A
Growth factors
22
Q
What colony stimulating factors go in to the myeloid line?
A
- CSF-Spleen
- CSF-GEMM
23
Q
Anemia, polycythemia, leukopenia, and thrombocytopenia are all diseases that affect what in bone marrow?
A
Blood production of bone marrow
24
Q
How do the following systemic diseases affect bone marrow?:
- Solid metastasizing tumors that spread to the marrow such as cancer and Hodgkin’s lymphoma
- Fever of Unknown Origin (FUO)
A
They affect blood production in bone marrow
25
Type of hereditary diseases that can affect bone marrow
Storage pool diseases such as Gauchers
26
Usual location a bone marrow aspirate is performed on adults
Posterior superior iliac crest
27
Usual location a bone marrow aspirate is done on children and infants
Top of tibia below the knee
28
Type of needle used for bone marrow aspirate
Jamshidi needle
29
Amount needed for bone marrow aspirate
0.5 - 1.5mL for hematology and an additional 5cc for other departments
30
2 diseases that could cause a "dry tap" (no aspirate)
- Myelofibrosis
- Aplastic anemia
31
Reasons an aspirate may not be collected
- Dry tap (Myelofibrosis or aplastic anemia)
- Not in the bone marrow
- Tumor
32
Preservative used for biopsy
Formalin
33
Marrow slide examination:
Childhood cellularity percentage
80%
34
Marrow slide examination:
Age 30-70 cellularity percentage
50%
35
Marrow slide examination:
How do you calculate the cellularity percentage for ages \>70?
100 - patient age = cellularity +/- 10%
36
Bone marrow cellularity
What would be the expected cellularity for an 82 year old patient?
100 - 82 = 18
**8 - 28%**
(18 +/-10%)
37
Under oil immersion, how many cells are counted during a bone marrow differential? What cells are counted?
500 to 1000 both red and white cells
38
What cells are not included in the M:E ratio?
Lymphs, monos, and plasma cells
39
What percentage of the bone marrow differential count will be comprised of neutrophilic myelocytes, metamyelocytes, bands, and segmented neutrophils?
50%
40
M:E Ratio:
350 neutrophilic blasts \>segs, eos, baso
75 lymphs, monocytes, and plasma cells
75 erythroid cells (blasts\>meta)
What is the M:E ratio?
350 / 75 = 4.7:1
41
Normal M:E ratio
3:1
42
How would myeloid hypoplasia effect the M:E ratio?
Myeloid cells would be decreased causing the M:E to be \< 3:1
43
How would erythroid hyperplasia effect the M:E ratio?
Erythroid hyperplasia would increase the red cells count causing the M:E ratio to be 1:1
44
What stains are performed on each bone marrow aspirate?
- Wright's stain
- Iron stain
45
Iron that is stored in the bone marrow is in what form?
Hemosiderin
46
What is hemosiderin composed of?
Iron and protein
47
Stain used to stain iron
Prussian Blue
48
Symptoms of anemia
- Tachycardia
- Shortness of breath
- Headaches
- Pallor
- Fatigue
49
TRUE or FALSE
Typical CBC results in anemia include:
-Decreased hemoglobin, hematocrit, and RBC count
TRUE
50
TRUE or FALSE
With most anemia, the M:E ratio is 1:1
TRUE
51
What MCV classifies as microcytic anemia?
\< 80fL
52
What MCV classifies as a macrocytic anemia?
\> 100 fL
53
What MCV classifies as a normocytic anemia?
80 - 100 fL
54
What is the cause of Microcytic, hypochromic anemias?
Inadequate production of some part of hemoglobin (iron, heme, globin)
55
Thalassemias have what abnormality?
Globin abnormality
56
2 Etiologic categories of macrocytic anemias
- Megaloblastic
- Non-Megaloblastic
57
Cause of megaloblastic anemias
Abnormal DNA synthesis
58
Cause of non-megaloblastic anemia
Increase in membrane lipids
59
TRUE or FALSE
Non-megaloblastic anemia will have an MCV \> 110
FALSE
Non-megaloblastic anemia will have an MCV \> 100 fL but \< 110 fL
60
This anemia is due to a slowdown in DNA synthesis in developing cells causing a shorter life span in the deficient cells
Megaloblastic anemia
61
What causes the defect in DNA replication that is seen in megaloblastic anemia?
A depletion of thymidine triphosphate, an immediate DNA precursor
62
If there is an increase in _______________ , it tells us there is possibly a B12 deficiency
Methylmalonyl Coenzyme A
| (MMA)
63
Being deficient in this causes slowed nuclear maturation and mitosis resulting in asynchrony in cells
Thymidine triphosphate
64
When the nucleus of a cell is immature and the cytoplasm is matured, this is referred to as what?
Asynchrony
65
Another name for B12
Cyanocobalamin
66
How is B12 absorbed in the body?
Through the intestine by Intrinsic Factor (IF)
67
Where is Intrinsic Factor produced?
Parietal cells of the stomach
68
What do the IF-B12 complexes attach for absorption?
To receptors on the ileal mucosal cells
69
What does B12 attach to after being absorbed?
Transcobalamin II
70
Where does the B12-transcobalamin II complex go?
Bone marrow
or
Liver for storage
(large amount is stored)
71
Where do we get B12 from in our diet?
Meat
Eggs
Dairy products
Liver
72
Where does folic acid come from in our diets?
- Leafy greens
- Meat
- Some fruits
73
What carries folate after it is absorbed?
Albumin
74
Where does albumin take folate in the body?
Bone marrow
or
Liver
(only a small amount is stored)
75
Once absorbed and transported, what 2 cofactors play an important role in DNA synthesis?
Folate and Vitamin B12
76
Any cell actively dividing or replicating will have a defective nucleus when either of what 2 cofactors are deficient?
B12 and Folate
77
A lack of intrinsic factor causes what anemia?
Pernicious Anemia
78
What tapeworm can cause a B12 deficiency?
*Diphyllobothium latum -* fish tapeworm
79
TRUE or FALSE
In pernicious anemia, folate cannot be absorbed
FALSE
Vitamin B12 cannot be absorbed properly due to a lack of intrinsic factor
80
An autoimmune disorder with autoantibodies produced by parietal cells causes what type of anemia?
Pernicious anemia
81
Pernicious anemia is typically found in which descent of people?
Northern European
82
How is pernicious anemia treated?
Vitamin B12 injections
83
Which is more common and why?
B12 deficiency
or
Folate deficiency
Folate deficiency because little to none is stored in the body
84
Clinical features of megaloblastic anemia
- Typical signs of anemia
- _Lemon-yellow pallor_
_-Smooth, sore tongue_
85
Clinical features of B12 deficient megaloblastic anemia
Neurologic manifestations from degeneration of myelin:
- tingling and numbness of extremities
- gait abnormalities
- psychosis due to defective methyl group metabolism
86
Key diagnostic features seen in the peripheral blood smear of megaloblastic anemia
- Hypersegmented neutrophils
- Macro-ovalocytes
87
Identify the anemia:
- Decreased retic
- Hypercellular bone marrow
- MCV \>110
- Decreased RBC, WBC, and PLT counts
- Macro-ovalocytes
- Hypersegmented neutrophils
Megaloblastic anemia
-either B12 or Folate deficiency but cannot distinguish without further testing
88
What is the term for a pyknotic cell causing a fragmented nucleus?
Karyorrhexis
89
Giant bands and giant metamyelocytes are a key findings in the bone marrow of which anemia?
Megaloblastic anemia
90
What is the term used to describe the cell the arrow is pointing to?
Karyorrhexis
91
What chemistry tests are elevated due to hemolysis with megaloblastic anemia?
LD and Bilirubin
92
Test that is used to differentiate between Pernicious Anemia and other B12 deficiencies
Schilling Test
93
Non-megaloblastic conditions (3)
- Liver disease
- Alcoholism
- Reticulocytosis
94
MCV will increase 1 fL for each \_\_\_% of retics
MCV will increase 1 fL for each **1%** of retics
95
What can cause the MCV to _appear_ macrocytic?
- Cold agglutinin
- High WBC count
- High glucose causing cells to swell
96
The following morphologic characteristics are seen in what class of anemia?:
- MCV \<80
- MCH and MCHC are decreased
- RDW is generally normal
Microcytic, hypochromic anemia
97
Where does most of the iron required by the cells come from?
Broken down RBCs
98
How much iron is needed for each mL of RBCs?
1mg
99
What regulates the absorption of iron in the body?
Mucosal cells in the GI tract
100
How much of the daily intake of iron from diet is actually absorbed?
10%
101
What enhances iron absorption?
Ascorbic acid (vitamin C) and using cast iron pots/skillets
102
What decreases iron absorption in the body?
Antacids
103
All of the following affect what?
- Type of iron in the food
- Other food that is ingested
- Acidity of stomach
- Availability of iron stores
Absorption of iron
104
Iron is transported from mucosal cells to the blood in what state?
Ferrous state (Fe2+)
105
What is the dietary form of iron?
Ferric (Fe3+)
106
What protein transports the ferric iron?
Transferrin
107
Number of iron atoms that transferrin can bind to at once
2 iron atoms per 1 transferrin molecule
108
Where are the 2 places transferrin will transport iron?
- Bone marrow
- Liver
109
Iron is stored as this in the liver
Ferritin
110
Transferrin can bind ____ - ____ mg of iron
240 - 280 mg
111
About what percentage of transferrin is bound with iron?
30%
112
How does celiac disease cause iron deficiency?
Celiac disease doesn't allow iron to absorb properly
113
What is significant about having an inherited mutation with matripase 2 protein?
It causes impaired absorption of iron leading to iron deficiency anemia
114
Most common cause of iron deficiency anemia
Increased blood loss
115
Sequence of development of iron deficient anemia
1. Iron storage depleted
2. Transport iron depleted
3. Functional iron depletion
116
Iron is required for _____ synthesis
Iron is required for **_heme_** synthesis
117
Stage of Iron depletion:
- Normal hemoglobin
- Normal serum iron
- Normal TIBC
- Decreased ferritin
Stage 1
Storage Iron Depletion
118
Stage of Iron depletion:
- Normal hemoglobin
- Decreased serum iron
- Increased TIBC
- Decreased ferritin
Stage 2
Transport Iron Depletion
119
Stage of Iron depletion:
- Decreased hemoglobin
- Decreased serum iron
- Increased TIBC
- Decreased ferritin
Stage 3
Functional Iron Depletion
120
Normal range for serum iron
50 - 160 ug/dL
121
Normal range for TIBC
250-400 ug/dL
122
What is TIBC?
Total Iron Binding Capacity = transferrin related test
123
Normal range for % transferrin saturation
20 - 55%
124
Normal range for ferritin for males
40 - 400 ng/mL
125
Normal range for ferritin for females
12 - 160 ng/mL
126
Classify the type of anemia
| (size and pallor)
Hypochromic, microcytic
127
What is iron overload also known as?
Hemosiderosis
128
The following may cause what?:
- Hemolytic anemia with massive transfusions
- Disorders of erythropoiesis where cells cannot be made and iron builds up
Hemosiderosis
129
What is the term for a more severe form of hemosiderosis
Hemochromatosis
130
What is the cause of Hereditary hemochromatosis?
A gene mutation (hereditary iron or transferrin receptor protein)
131
The following results are seen in what disorder?
- Abnormal AST and ALT (LFTs)
- Increased serum iron
- Increased % transferrin saturation
- Increased serum ferritin
- Increased hgb
- Increased HCT
Hemochromatosis
132
How is hereditary hemosiderosis treated?
Therapeutic phlebotomy
133
How is transfusion related hemosiderosis treated?
Chelation therapy
Patient is given desferrioxamine which binds to iron and gets excreted in urine
134
Thalassemia, Anemia of Chronic Disease/Inflammation, Lead poisoning, and Sideroblastic Anemia are all examples of what type of anemia?
Microcytic anemia
135
An inherited disorder in which the globin chain is not produced in adequate amounts
Thalassemia
136
This is the most common anemia among hospitalized patients
Anemia of Chronic Disease/Inflammation
137
This hormone is an acute phase reactant that regulates the absorption of iron in the intestines and also the release of iron from macrophages.
Hepcidin
138
What produces hepcidin?
The liver
139
This acute phase reactant is an iron binding protein located in the granules of neutrophils. It is involved in preventing phagocytized bacteria from using intracellular iron for their own metabolic processes
Lactoferrin
140
The following lab results are seen with which type of anemia?:
- Decreased serum iron
- Decreased TIBC
- Increased serum ferritin
- normal soluble transferrin receptors (sTfRs) - newer test
Anemia of Chronic Disease/Inflammation
141
Treatment of Anemia of Chronic Inflammation
- Treat with erythropoietin, given with iron b/c the body's stored iron remains unavailable
- Alleviate the causative condition
142
Lead poisoning is caused by lead blocking the production of what in several spots?
Lead poisoning blocks heme production
143
This microcytic anemia causes:
-Interference in the conversion of aminolevulinic acid (ALA) to porphobilinogen (PBG)
and
-Interference in the incorporation of iron into protoporphyrin IX by ferrochetalase
Lead poisoning
144
This microcytic anemia will interfere with the breakdown of ribosomal RNA creating coares basophilic stippling and a low MCV
Lead poisoning
145
TRUE or FALSE
Basophilic stippling is diagnostic for lead poisoning
FALSE
146
In this microcytic anemia the following occurs:
- Cells cannot use available iron
- The iron is trapped in the cell
- Iron will form pappenheimer bodies in mature cells
Sideroblastic anemia
147
This picture depicts a hallmark representation of what microcytic anemia?
Sideroblastic anemia
148
What is considered "hallmark" for sideroblastic anemia?
Dimorphic RBCs and ringed sideroblasts
149
MCV, MCH, and MCHC are lowest with which microcytic anemia?
Thalassemia
150
Will the RDW be normal, elevated, or decreased with iron deficiency anemia?
Elevated
151
Will RDW be normal, elevated, or decreased with Thalassemia?
Normal
152
What is included in iron studies?
- Serum iron
- Total Iron Binding Capacity (TIBC)
- % Transferrin Saturation
- Serum Ferritin
153
What is measured in serum iron?
The amount of iron bound to transferrin in circulation
154
What does TIBC measure?
The amount of transferrin bound and unbound with iron
It is measuring the binding ability of transferrin
155
How is % transferrin saturation calculated?
Serum iron / TIBC x 100
156
Normal range for soluble transferrin receptors
1.15 - 2.75 mg/L
157
The amount measured in this test is based on intracellular iron and is an indicator of functional iron available in cells
Soluble transferrin receptors (sTfR)
158
TRUE of FALSE
sTfR is increased in Anemia of Chronic Inflammation
FALSE
Normal in Anemia of Chronic Inflammation
159
TRUE or FALSE
sTfR is increased in IDA
TRUE
160
When does free erythrocyte protoporphyrin accumulate?
When iron is NOT available
161
Free erythrocyte protoporphyrin will be increased, decreased, or normal in IDA?
Increased
162
With which anemia is knowing the value of free erythrocyte protoporphyrin is most valuable?
Lead poisoning due to ferrochelatase impairment
163
Normal value of free erythrocyte protoporphyrin
\< 80 ug/dL
164
A storage form of iron mostly found in bone marrow
Hemosiderin
165
Red cells having a "shaggy" cytoplasm is seen with what anemia?
Iron deficiency anemia
166
Name the hypochromic, microcytic anemia
Iron Deficiency Anemia
167
Name the hypochromic, microcytic anemia
Thalassemia
168
Name the hypochromic, microcytic anemia
Anemia of Chronic Inflammation/Disease
169
Name the hypochromic, microcytic anemia
Sideroblastic anemia
170
Name the hypochromic, microcytic anemia
Lead poisoning
171
Free erythropoietin is also known as
Zinc protoporphyrin (ZPP)
172
What are the 3 types of normocytic, normochromic anemia?
- Hemolytic
- Aplastic Anemia
- Acute Blood loss
173
In this category of N/N anemia cells are not made. The building blocks are present and RBCs look normal but there just aren't enough of them.
Aplastic anemia
174
In this category of N/N cells are broken down at an increased rate
Hemolytic anemias
175
N/N anemia:
- Cellular areas of bone marrow are replaced by fat cells
- Caused by toxic, radiant, or immunologic injury to pluripotential cells
Aplastic anemia
176
Normocytic/Normocytic anemias are categorized based on increased, decreased, or normal \_\_\_\_\_\_
Reticulocyte count
177
TRUE or FALSE
Aplastic anemia is always permanent and requires a bone marrow transplant - but this may not always work
FALSE
It can be permanent but only if all of the pluripotential cells are damaged.
178
Types of congenital aplastic anemia
- Fanconi anemia
- Dyskeratosis Congenita
- Scwachman-Bodian-Diamond Syndrome
179
This inherited aplastic anemia is an autosomal recessive chromosomal instability disorder
Fanconi Anemia
180
In this aplastic anemia you will see:
-Pancytopenia, a decrease in reticulocytes, hypocellular bone marrow
as well as
-Skin pigmentation, short stature, and hypogonadism
Fanconi Anemia
181
This inherited aplastic anemia is a bone marrow failure disease
Dyskeratosis Congenita
182
With this inherited aplastic anemia you will see:
- Abnormal skin pigmentation (dark spots with white dots in them)
- Dystrophic nails (look almost like a fungal infection)
- Oral leukoplakia (very white thrush-looking tongue)
- Bone marrow failure
Dyskeratosis Congenita
183
This inherited aplastic anemia resembles cystic fibrosis
Shwachman-Bodian-Diamond Syndrome
184
Name the inherited aplastic anemia:
- Pancreatic insufficiency
- Cytopenia
- Skeletal abnormalities
- Predisposition for hematologic malignancies
- Neutropenia and immune dysfunction
- Normal sweat chloride (will differentiate it from cystic fibrosis)
Shwachman-Bodian-Diamond Syndrome
185
What percentage of aplastic anemia is diagnosed as idiopathic?
50-75%
186
Secondary aplastic anemia accounts for what percentage of cases?
25%
187
Causes of secondary aplastic anemia
- Chloramphenicol, an old antibiotic
- Industrial chemicals such as benzene
- Insecticides such as DDT
188
What can cause acquired aplastic anemia?
- Radiation exposure
- Infections such as hepatitis, HIV, Epstein-Barr, or TB
189
TRUE or FALSE
You will see pancytopenia and increased infections with aplastic anemia
TRUE
190
What is the survival rate for aplastic anemia after bone marrow transplant?
80%
191
What anemia is this bone marrow indicative of?
Aplastic anemia
192
This is a selective decrease in the red cell commited stem cells resulting in a temporary reduction in RBC production. It often follows a parvovirus infection.
Pure Red Cell Aplasia
193
What does parvovirus infection cause in children?
Fifth Disease
194
What is due to clonal proliferation of pluripotential stem cells with incomplete maturation of marrow precursors?
Myelodysplastic syndromes
195
These disorders are due to a chromosomal defect in stem cells from oncogenes, environmental elements, or secondary to chemotherapy and radiation from previous cancers
Myelodysplastic disorders
| (MDS)
196
In \_\_\_\_, apoptosis appears to be increased early in the disease
MDS
197
This anemia is usually resistant to any therapy. Pancytopenia including reticulocytopenia, is present. The bone marrow is normo- or hypercellular with increased iron stores.
Refractory anemia
198
In this anemia, erythroid hyperplasia with nuclear budding in erythroid precursors can be seen in the bone marrow
Refractory Anemia
199
TRUE or FALSE
Refractory anemia can be cured with hematopoietic stem cell transplant
TRUE
200
The cause of this NC/NC anemia is mostly due to decreased erythropoietin
Anemia of renal disease
201
How is anemia of renal disease treated?
Erythropoietin therapy
202
What other organs may contribute to anemia of renal disease disorder?
Thyroid and liver
203
Anemia of chronic disorders is the most common anemia of what type of people?
Hospitalized patients
204
What anemia is observed with infections, autoimmune disorders (SLE, RA), and malignancies?
Anemia of chronic disorders
205
Name the anemia:
- Cytokines are produced by the immune system in response to immune or tumor stimulus
- Erythropoietin is inhibited
- Macrophages become stimulated and will not release iron after normal RBC breakdown in the spleen
- Hepcidin protein is involved
Anemia of chronic disorders
206
Acute phase reactant that increases in inflammation/infection
- Iron regulator produced by hepatocytes
- Increased in anemia of chronic disorder
Hepcidin
207
This anemia results from marrow infiltration with subsequent damage to hematopoietic microenvironment and replacement of normal cells.
-Due to metastatic carcinoma whereby primary cancer cells go to bone marrow and start to proliferate
Myelophthisic anemia
208
Extramedullary hematopoiesis occurs with this anemia producing less functional cells.
Myelophthisic anemia
209
What anemia is depicted in this picture?
- Tear drop RBCs
- Leukoerythroblastic cells
- NRBCs
Myelophthisic anemia
210
This NC/NC anemia leads to cardiovascular collapse and shock
Acute blood loss
211
What percentage of blood loss will result in shock and death?
50%
212
What percentage of blood loss with result in major symptoms?
30-40%
213
What are the 2 major categories of NC/NC anemia?
Aplastic and hemolytic
214
With normocytic/normochromic anemias, what CBC results are normal and what results are decreased?
Normal: indices (MCV, MCH, MCHC)
Decreased: Hgb, HCT, RBC count
215
What are the classifications of hemolytic anemia? (6)
- Intrinsic
- Extrinsic
- Acquired
- Inherited
- Acute
- Chronic
216
This classification of hemolytic anemia is intracellular - due to a defect of the cell
Intrinsic
217
This classification of hemolytic anemia is extracellular - due to a defect outside the cell.
Extrinsic
218
Classification of hemolytic anemia that is sudden and/or episodic
Acute
219
Classification of hemolytic anemia that occurs over time and may not be evident if the bone marrow is able to compensate.
Chronic
220
Classification of hemolytic anemia that is passed to offspring by parents and is due to a mutant gene
Inherited
221
Hemolytic anemia classification that is developed in individuals who were previously normal but exposed to a chemical/agent/ or condition
Acquired
222
Hemolytic anemias:
Most intrinsic defects are \_\_\_\_\_\_, while most extrinsic defects are \_\_\_\_\_\_\_.
Most intrinsic defects are **_inherited,_** while most extrinsic defects are **_acquired._**
223
What hemolytic anemia is intrinsic but acquired instead of inherited?
Paroxysmal Nocturnal Hemoglobinuria
224
Examples of acute hemolytic anemia
- Paroxysmal Nocturnal Hemoglobinuria
- Hemolytic Transfusion Reaction
225
Examples of chronic hemolytic anemia
-G6PD deficiency
226
All of the following are examples of what classification of hemolytic anemia?:
- Abnormalities of the RBC membrane
- Defective enzymatic pathways
- Defective hemoglobin molecule
Intrinsic hemolytic anemia
227
All of the following are examples of what classification of hemolytic anemia?:
- Malaria parasitic infection
- Antibodies to an RBC antigen
Extrinsic hemolytic anemia
228
Term that means the cell is destroyed by the spleen
Extravascular
229
Term that means the cells is destroyed in the vessel
Intravascular
230
Percentage of cell destruction that is intravascular
10%
231
Percentage of cell destruction that is extravascular
90%
232
Compensated or uncompensated?:
-Little to no anemia
Compensated
233
Compensated or Uncompensated?:
Red cell life span is usually only 15-20 days
Uncompensated
234
In compensated bone marrow response, the bone marrow is able to increase its output how much?
6x - 8x
| (six-fold to eight-fold)
235
-Autosomal dominant
- Defects in proteins that disrupt the _vertical_ interactions between transmembrane proteins and cytoskeleton proteins of red cells
- Ankrin and Spectrin
-Results in a destabilization of the lipid bilayer allowing lipids to escape
Hereditary spherocytosis
236
In this disorder the cell is not able to deform due to decreased surface-to-volume ratio so macrophages in the spleen will remove the cell.
The disorder is more common in northern European descent
Hereditary spherocytosis
237
Clinical symptoms of this disorder include:
- Mild jaundice
- Anemia
- Splenomegaly
Lab Findings:
- MCV normal or slightly decreased
- MCH elevated
- MCHC \>36% (hallmark)
- Increased LD and Bilirubin
- Increased osmotic fragility
- Reticulocytosis
Hereditary spherocytosis
238
Measures the surface-to-volume ratio of RBCs
- Cells are placed in graded hypotonic salt (saline) solutions
- Water enters cell, cell swells, and bursts
Osmotic fragility
239
What is represented by A
Target cells and elliptocytes
240
What does B represent?
Normal cells
241
What does C represent?
Spherocytes
242
Normal range of osmotic fragility
Hemolysis begins at 0.45% NaCl
100% hemolysis occurs between 0.35-0.30%
243
When does hemolysis begin for hereditary spherocytosis in osmotic fragility?
0.65% NaCl
244
Treatment for hereditary spherocytosis
Splenectomy in severe cases
245
Autosomal dominant hereditary membrane defect involving the _horizontal_ bonds on the skeleton of RBCs
Hereditary elliptocytosis
246
This membrane defect is caused by an imbalance of cations and is more commonly acquired due to acute alcoholism, malignancy, or medications.
Stomatocytes
247
This membrane defect condition is rare and usually inherited. Fragmentation, microspherocytosis, and elliptocytosis are seen. RBCs show a marked thermal sensitivity- incubated cells between 41C-45C will fragment.
Pyropoikilocytosis
248
This membrane defect is observed in:
-Acquired liver disease
and
- Congenital abetalipoproteinemia (rare)
- No LDL/VLDL
- Fat malabsorption, ataxia, neuropathy, retinitis pigmentosa, acanthocytosis
Acanthocytes
249
This deficiency is transmitted a by sex-linked, mutant gene and is more common in males
G-6-PD Deficiency
250
When this is deficient NADP cannot be converted to NADPH, glutathione is reduced, hemoglobin aggregates or precipitates (Heinz Bodies), and premature destruction of red cells occurs.
G-6-PD
251
Relatively common disorder in African American males and Asians. Most people never suffer any clinical manifestations because the bone marrow will compensate.
G-6-PD deficiency
252
If you have this, you will have a sensitivity to fava beans and primaquine (an anti-malarial drug) could induce a hemolytic episode
G-6-PD deficiency
253
Qualitative test for G-6-PD deficiency
Fluorescent Spot Test
254
Second most common enzyme deficiency
-Involved in Embden-Meyerhoff pathway
Pyruvate Kinase Deficiency
255
Acquired intracellular defect with intravascular hemolysis
Paroxysmal Nocturnal Hemoglobinuria
256
In PNH, what is deficient?
CD 55 - Decay Accelerating Factor
CD 59 - Membrane inhibiting of Reactive Lysis (MIRL)
These proteins prevent normal cells from complement destruction
257
Screening test for PNH
Sugar Water Test
-promotes binding of complement to red cell membrane; complement-sensitive PNH red cells are lysed while normal cells are unaffected
258
Confirmation test for PNH
Ham's Test (Acidified serum lysis test)
259
PNH treatment
- Treat symptoms - support therapy
- Treat complications
260
Average survival period for PNH
10 years
-May become AML
261
What causes autoimmune hemolytic anemia?
Primary - idiopathic
Secondary to autoimmune disorder or cancer- SLE, RA, CLL, lymphoma
262
2 types of autoimmune hemolytic anemias
- Warm-reactive antibodies (IgG)
- Cold-reactive antibodies (IgM)
263
70% of all cases of autoimmune hemolytic anemias are due to this autoantibody
Warm-reactive (IgG)
264
What will differentiate warm-reactive autoantibodies from spherocytosis?
Direct antiglobulin test
- Positive with warm auto
- Negative with spherocytosis
265
When treating a patient with a warm autoantibody, what is done only as a last resort?
Transfusion
266
Cold-reactive autoantibodies are most often observed when?
Secondary to an infection such as:
-Mycoplasma pneumonia
or
-Infectious mononucleosis
267
Clinical findings of cold autoantibodies
Acrocyanosis- cyanosis in extremities
Anemia symptoms
268
With this autoimmune hemolytic anemia the specimen will agglutinate as it cools to room temperature and you will observe agglutinated red cells on the peripheral blood smear
Cold autoantibody
269
Non-immune hemolytic anemia also referred to as sports anemia. Caused by trauma to cells from physical disruptions
March hemoglobinuria
270
This non-immuno hemolytic anemia is a serious life-threatening disease in which cells are fragmented by fibrin in the vessels or a defective heart valve.
Microangiopathic anemia
271
Non-immune hemolytic anemia can be caused by what chemical or physical agents?
- Copper
- Water (drowning)
- Insect venom
- Drugs
- Chemicals
- Heat stroke
272
What microorganisms can cause a non-immune hemolytic anemia?
- Malaria
- other bateria and viruses producing toxins
273
This microorganism is the most common cause on non-immune hemolytic anemia in the world
Malaria
274
Will the following be increased, decreased, or normal in hemolytic anemias?:
- Unconjugated bilirubin
- LD
- Reticulocytes
- MCV
- Red cells
- Haptoglobin
- HCT
- Urine urobilinogen
Increased:
- unconjugated bilirubin
- LD
- Reticulocytes
- Urine urobilinogen
- Bone marrow red cells
- MCV slightly if retic % is increased
Decreased:
- Red cells in peripheral blood
- Haptoglobin
- HCT
Normal:
-MCV if retic % is normal
275
Urine hemoglobin and hemosiderin are increased in what type of hemolysis?
Intravascular hemolysis
276
What test is specific for autoimmune hemolytic anemia?
Direct antiglobulin test (DAT)
277
What test is specific for hemoglobinopathies?
Hemoglobin electrophoresis
278
What test is specific for G6PD deficiency?
Heinz bodies
and
G6PD assay when patient is not in a crisis
279
Test that is specific for hereditary spherocytosis and elliptocytosis
Osmotic fragility
280
What test is specific for PNH?
Sucrose hemolysis (screening)
and
Ham Test (confirmation)
281
What is hemoglobin A comprised of?
2 Alpha chains and 2 Beta chains
282
Percentage of adult hemoglobin that is Hgb A
95%
283
What is Hemoglobin A2 comprised of?
2 Alpha chains and 2 Delta chains
284
Percentage of hemoglobin that is A2
~3%
285
What is hemoglobin F comprised of?
2 Alpha chains and 2 Gamma chains
286
Percentage of hemoglobin that if F
~1%
287
A chronic hemolytic anemia resulting from an inherited alteration of the globin chain.
Valine is substituted for glutamic acid on the sixth position of the Beta chain
Sickle Cell anemia
288
Why do the red cells form sickle shapes in sickle cell anemia?
Valine is insoluble and hydrophobic
-so when the red cell is deoxygenated, polymerization occurs causing the hemoglobin molecules to combine and "flatten"
289
- Autosomal recessive
- 7-8% of African Americans have the trait
- .25% of African Americans have homozygous disease
- Disease is found in Africa, Middle East, and USA
- Associated with malaria
Sickle Cell Anemia
290
Screening tool for Hemoglobin S
Solubility test
291
A turbid result of the solubility test is _____ for hgb S
Positive
292
What can cause a false negative on a sickle solubility test?
- Increased levels of hgb F
- If the patient is very anemic (\<7.0 g/dL hgb)--add 50ul of blood to the reducing agent--
293
False positive sickle solubility
- Too much sample
- Hyperlipidemia
294
Order of movement for hemoglobin on cellulose acetate agar
| (from cathode to anode)
- (cathode)
origin
Hgb C
Hgb S
Hgb F
Hgb A
+ (anode)
295
What is the pH of cellulose acetate agar?
8.4 pH
296
pH of citrate agar
6.0-6.2 pH
297
What is citrate agar used for in hemoglobin electrophoresis?
To verify Hgb S or C from other variants
298
Mild chronic hemolytic anemia with splenomegaly resulting from glutamic acid being substituted by lysine on the sixth position of the Beta chain. Found in 2-3% of African Americans
Hemoglobin C
299
What are the arrows pointing at?
Hemoglobin S - Sickle cells
300
What is the arrow pointing to in the picture?
Hemoglobin C crystals
301
What are the arrows pointing to?
Hemoglobin SC
302
This hemoglobin variant causes a splice site, causing transcription of mRNA which results is both qualitative and quantitative defects. A mild chronic hemoltic anemia forms as a result.
Hemoglobin E
303
A beta chain variant (a2B2)26Glu->Lys causes this hemoglobin variant which is commonly found in Southeast Asian descent
Hemoglobin E
304
This is the most common single gene disorder in humans
Thalassemia
305
Due to a reduced rate of a globin chain
Thalassemia
306
What is the term used to describe the area in which thalassemia is most often found
"Thalassemia belt"
307
Having a thalassemia minor means you're \_\_\_\_\_\_\_\_\_\_\_\_
(heterozygous/homozygous)
Heterozygous
308
Thalassemia major is \_\_\_\_\_\_\_
| (homozygous/heterogous)
Homozygous
309
Genetic disorder resulting in abnormal amount or function of mRNA, producing reduced or absent beta globin chains
Beta thalassemia
310
Found in people from Mediterranean region, Saudi Arabia, Southeast Asia, and Africa
Beta thalassemia
311
Heterzygous state of beta thalassemia with no hematologic abnormalities or clinical symptoms
Beta thalassemia silent carrier
312
Heterzygous state of beta thalassemia with mild hemolytic anemia, microcytic/hypochromic RBCs, no clinical symptoms
Beta thalassemia minor
313
Homozygous state of beta thalassemia with severe hemolytic anemia, microcytic/hypochromic RBCs, severe clinical symptoms, and transfusion dependent
Beta thalassemia major
314
Type of beta thalassemia: Mild to moderate hemolytic anemia, microcytic/hypchromic RBCs, moderate clinical symptoms, transfusion independence
Beta thalassemia intermedia
315
This Thalassemia has:
- No Hgb A
- Most of the Hgb is Hgb F with increased Hgb A2
- Hgb value is very low; 3-7 g/dL
- Marked expansion of marrow spaces due to ineffective erythropoiesis
- Extreme skeletal changes
- Marked aniso, poik, mciro, and hypo
- Target cells, NRBCs, and basophilic stippling are seen on peripheral blood smear
Beta Thalassemia Major
aka
Homozygous Beta Thalassemia
316
What thalassemia is depicted in these pictures?
Beta Thalassemia Major
| (Homozygous Beta Thalassemia)
317
What is the treatment for Beta thalassmeia major?
- Blood transfusions throughout lifetime
- Hematopoietic stem cell transplant
- Possible gene therapy
318
This beta thalassemia causes a mild microcytic, hypochromic anemia with target cells and basophilic stippling. Patients have few symptoms except during pregnancy.
-May resemble IDA
Beta thalassemia trait/minor
319
Which thalassemia is depicted in the picture?
Beta thalassemia trait/minor
320
What chromosome contains the genes that control beta, gamma, and delta chains?
Chromosome 11
321
What chromosome comtains the genes that control alpha chains?
Chromosome 16
322
Number of genes on chromosome 11 that control beta, gamma, and delta chains
2
323
Number of genes on chromosome 16 that control alpha chains
4
324
Alpha Thalassemia:
What number of gene deletions has no clinical symptoms, normal hematology values, and affects 30% of all African Americans?
1 gene deletion
325
Alpha Thalassemia:
What number of gene deletions has no clinical symptoms, creates a slight hypo, micro anemia, and affects Asians?
2 gene deletions cis
326
This alpha thalassemia is a 2 gene deletion in which the deletions are on the same chromosome
2 gene deletion **_cis_**
327
Alpha Thalassemia:
What number of gene deletions has no clinical symptoms, creates a slight hypo/micro anemia, and affects mostly Blacks?
2 gene deletion **_trans_**
328
This alpha thalassemia is a 2 gene deletion in which the deletions are on opposite chromosomes
2 gene deletion alpha thalassemia **_trans_**
329
Alpha Thalassemia:
This number of gene deletions causes:
- Severe hemolytic anemia
- Is name Hgb H disease, causes patients to have mostly Hgb H (tetramer of beta chains)
- Is observed in Asians
3 gene deletions
330
Alpha Thalassemia:
This number of gene deletions causes:
- Hydrops Fetalis
- Always fatal
- No Hgb A, A2, or F
- All Hgb is Bart's Hgb (tetramer of gamma chains)
- Observed in Asian descent
4 gene deletion
331
With this disorder, there is no switch from fetal hgb to adult hgb. Beta chains are not produced. Homozygous individuals have 100% Hgb F. Carriers have 15-35% Hgb F.
Hereditary Persistence of Fetal Hemoglobin
HPFH
332
This test is used to visualize Hgb F in peripheral smears
Kleihauer Betke Test
333
In the Kleihauer Betke test, how will RBCs containing adult hemoglobin appear?
as "ghost" RBCs
334
Constant Spring, M Hemoglobin, Hemoglobin Lepore, Hgb Hammersmith, and Hgb Gun Hill are all examples of what?
Abnormal hemoglobins
335
Increased or Decreased:
This oxygen affinity is ovserved in erythrocytosis (such as PV) because hemoglobin does not released O2 to the tissues.
-Causes erythropoietin to be activated due to decreased oxygen tension in the blood
**_Increased_** oxygen affinity
336
Increased or Decreased:
This oxygen affinity is due to more oxygen being released to the tissue so erythropoietin is not activated causing a slight anemia.
**_Decreased_** oxygen affinity
337
Hgb Kempsey is an example of _________ oxygen affinity causing a left shift in the oxygen dissociation curve.
**_Increased_**
338
Hgb Kansas is an example of ________ oxygen affinity causing a right shift in the oxygen dissociation curve.
**_Decreased_**
339
What is caused due to an abnormality in the globin chains in the hemoglobin molecule?
Hemoglobinopathies
340
How do we identify hemoglobinopathies?
Hemoglobin electrophoresis
341
How do you calculate the relative reticulocyte count?
342
Normal range for relative retic count
0.5 - 2.5%
343
How do you calculate the absolute reticulocyte count?
344
Normal range for absolute retic count
20,000 - 115,000/uL
345
How do you calculate the corrected retic count to adjust for anemia?
346
Patients with a hematocrit of 35% should have what corrected retic value?
2-3%
347
Patients with a hematocrit \< 25% should have what corrected retic value?
3-5%
348
This calculation adjusts for prolonged peripheral maturation time for reticulocytes
Reticulocyte production index (RPI)
349
What are the calculations for the reticulocyte production index?
350
What RPI value indicates adequate bone marrow response?
RPI \> 3
351
What RPI value indicates inadequate erythropoietic response?
RPI \< 2
352
Fat to cell ration seen with aplastic bone marrow
90: 10
- normal = 50:50
353
Most anemias will have what type of cell hyperplasia in the bone marrow?
Erythroid hyperplasia
| (RBCs)
354
What would you expect to see in a bone marrow smear for possible megaloblastic anemia?
- Asynchrony
- Hypersegmented neutrophils
- Giant metamyelocytes and bands
355
What tests will help distinguish the different microcytic anemias?
-Hemoglobin electrophoresis to detect:
~Thalassemia, Sickle, Hgb C
~If no Hgb A, disease is homozygous
~Kleihauer Betke stain to detect increased fetal hgb in thalassemia or HPFH
-Ferritin, iron, TIBC to detect IDA
356
Tests used to distingiush normocytic anemias
- Sickle solubility test: cannot distinguish disease from trait
- Direct antiglobulin test (DAT): for AIHA
- Osmotic fragility: will diagnose hereditary spherocytosis or elliptocytosis
- Enzyme deficienes: G6PD deficiency will have Heinz Bodies and a deficient G6PG screen
- Sucrose hemolysis, Ham test, and Flow cytometry for PNH: lysis positive
- Haptoglobin, urine hemosiderin, urine urobilinogen: determines intravascular vs extravascular hemolysis
- Reticulocytes: indicates if hemolysis or hypoproliferative disorder
- Bilirubin and LD: increased in hemolytic anemia
357
Tests used to distinguish macrocytic anemia
- B12 and folate levels
- Erythropoietin level increased: intramedullary hemolysis
- Schilling test: detects Pernicious Anemia
- Liver enzymes increased in liver disease
- Bone marrow for myelodysplasia: pre-leukemia
358
Red cell inclusions:
- DNA
- Seen in post-splenectomy
- Megaloblastic anemias and some hemolytic anemias
- Small single, deep blue, round granule at periphery of cell
Howell Jolly Body
359
Red cell inclusions:
- RNA
- Associated with decreased RBC survival/hemorrhage, erythroid hyperplastic marrow
- Polychromasia with Wright's stain
Reticulocyte
360
Red cell inclusions:
- Iron
- Seen in sideroblastic anemia and thalassemia
- Subtle pale dots near periphery of cell
Pappenheimer body
361
Red cell inclusions:
- Precipitated hemoglobin
- Seen in G6PD deficiency
- Can only be seen with supravital stain
Heinz Body
362
Red cell inclusions:
-Crystallized hemoglobin
C crystal
363
Red cell inclusions:
- Iron
- Nucleated red blood cell precursor with at least five granules that circle at least 1/3 of the nucleus
Ringed sideroblast
364
Red cell inclusions:
- RNA aggregates
- Seen in thalassemia (fine) and lead poisoning (coarse)
Basophilic stippling
365
Red cell inclusions:
- DNA
- Usually a metarubricyte
- Always abnormal in adult peripheral blood
NRBC
366
How do is the automated hematocrit calculated?
367
Common cause for Folate deficiency
Diet
368
What is increased in hemochromatosis?
Iron
369
What anemia is found in mononucleosis?
Cold agglutinin (IgM)
370
What globin chains are in Hgb A?
2 Alpha
2 Beta
371
What globin chains are in Hgb A2?
2 Alpha
2 Delta
372
What chains are in Hgb F?
2 Alpha
2 Gamma
373
What chains are in Hgb H?
4 Beta
374
What chains are in Bart's Hemoglobin?
4 Gamma
375
Percentage of transferrin bound to iron
30%
376
How are intravascular and extravascular hemolysis distinguised?
Urine hemosiderin
| (increased with intravascular)
377
Tests utilized in the detection of hemolytic anemia
- Bilirubin: increased
- LD: increased
- Haptoglobin: decreased
- Urine hemosiderin: increased
378
What is the reticulocyte value for hemolytic anemias?
Increased
379
What is the reticulocyte value for anemias due to nutritional deficiencies?
Decreased until the nutritional need is met
380
Which of the anemias are life threatening?
- Alpha Thalassemia major (4 gene deletion)
- Microangiopathic Anemia (DIC, HUS, TTP)
381
How can Hgb A with Hgb S be confirmed?
Hemoglobin electrophoresis using citrate agar
382
How can IDA and anemia of chronic disease be differentiated?
Ferritin and TIBC
IDA: Ferritin is decreased and TIBC is increased
Anemia of chronic disease: Ferritin and TIBC are decreased
383
What's the purpose of the Schilling test?
Detects malabsorption of B12 found in Pernicious Anemia
384
What is the breakdown product of hemoglobin?
Urobilinogen
385
What are the products of heme synthesis?
- Protoporphyrin
- Uroporphyrin
- Coproporphyrin
386
Which thalassemia is more serious?
Alpha thalassemia major
387
What microscopic power is used to view bone marrow megakaryocytes?
10X, low power
388
What do karyorrhexis and asynchrony indicate?
Defective DNA synthesis
389
At what point do normal RBCs lyse in osmotic fragility?
~ 0.45 - 0.5% NaCl with complete hemolysis by 0.3%
390
Which anemia type is found in liver disease?
Macrocytic
391
Which chemistry tests are elevated in hemolytic anemia?
Bilirubin and LD
392
Which group of anemias has the most polychromasia?
Hemolytic anemias
393
Ringed sideroblasts on an iron stain indicate what?
Sideroblastic anemia
394
Are hyper-segmented neutrophils reported?
Yes
395
What is the bone marrow fat to cell ratio in aplastic anemia?
90:10
396
If the wrong type of blood is transfused, what type of hemolysis is found?
Intravascular
397
Fetal hemoglobin content for newborns
60-90%
398
Fetal hemoglobin content for HPFH heterozygous
15 - 35%
399
Fetal hemoglobin content for HPFH homozygous
100%
400
Fetal hemoglobin content for sickle cell trait
Normal, ~1%
401
What is the M:E ratio for erythroid hyperplasia?
1:1
402
Calculate the M:E ratio-
-During a bone marrow analysis, 370 myeloid cells are counted, 130 erythroid cells are counted.
370 myeloid : 130 erythroid
=
2.8 : 1
403
What is the normal M:E ratio?
3:1
404
What is the M:E ratio in anemia?
1:1
405
What percentage of white blood cells are the more mature cells in normal bone marrow?
50% of neutrophils are myelocytes, metamyelocytes, bands, and segs
406
What is an advantage of using automated instruments?
Increased precision
407
When is basophilic stippling observed?
- Thalassemia
- Lead poisoning
- Megaloblastic anemia
- Sickle Cell anemia
