Neoplasia/Hematology - Mechanisms of Disease - Nutritional/Hypoproliferative Anemias; Hemolytic Anemias; Transfusion Medicine Flashcards
(215 cards)
1
Q
Anemias are typically caused by what three categories of etiology?
A
- Blood loss
- Underproduction
- Destruction
2
Q
Where is iron absorbed?
Where is folate absorbed?
Where is cobalamin absorbed?
A
Proximal duodenum
proximal jejunum
Terminal ileum
3
Q
What is the normal hemoglobin range for male patients?
A
14 - 16 mg/dL
4
Q
What is the normal hemoglobin range for female patients?
A
12 - 14 mg / dL
5
Q
What is the range of normal hematocrits?
A
36 - 50%
6
Q
What does an MCV measure?
A
The mean corpuscular volume — how large each RBC is
7
Q
What does the MCHC measure?
A
The mean hemoglobin concentration per RBC
8
Q
What does the RDW measure?
A
Cell size uniformity and variability — Is anisocytosis present? Are all the RBCs a similar size?
9
Q
What is the reticulocyte count used to determine?
A
Bone marrow response
10
Q
What is the range of normal MCV values?
A
80 - 100 fL
(normocytic)
(microcytic) < 80 (normocytic) 100 > (macrocytic)
11
Q
Nutritional anemias typically revolve around what main dietary factors?
A
Iron;
B9;
B12
12
Q
A lack of Iron leads to anemia via decreased _______ synthesis.
A lack of B9 leads to anemia via decreased _______ synthesis.
A lack of B12 leads to anemia via decreased _______ synthesis.
A
A lack of Iron leads to anemia via decreased heme synthesis.
A lack of B9 leads to anemia via decreased DNA synthesis.
A lack of B12 leads to anemia via decreased DNA synthesis.
13
Q
Where is iron absorbed into the body?
A
The proximal duodenum
(DMT1 and heme transporters)
14
Q
How much iron is typically lost per day?
A
1 mg
(more during menstruation)
15
Q
Only Fe_?_ is and _______ iron are absorbed.
A
Only Fe2+** (ferrous) and **heme iron are absorbed.
16
Q
Absorbed iron is bound to what in mucosal epithelium?
What transporter allows it to leave the enterocytes to reach the bloodstream?
A
Ferritin;
ferroportin 1
17
Q
What substance is released by the liver in order to block ferroportin 1 (not allowing iron to be absorbed from enterocytes into the bloodstream)?
A
Hepcidin
18
Q
Hepcidin is up-regulated by the liver in response to ______ hepatic iron levels.
A
Hepcidin is up-regulated by the liver in response to increased hepatic iron levels.
(See image — Hepcidin blocks iron uptake from enterocytes to the bloodstream.)
19
Q
Where are the major iron storage sites of the body?
A
The reticuloendothelial system
/
the bone marrow
20
Q
What are the three main serum iron studies?
A
- Serum ferritin
- Serum iron
- Total iron-binding capacity (TIBC)
21
Q
Describe iron deficiency anemia in terms of the following:
RBC count:
H&H:
MCV:
MCHC
RDW:
A
Describe iron deficiency anemia in terms of the following:
RBC count: low
H&H: low
MCV: < 80 fL
MCHC: low
RDW: increased
22
Q
Hypochromic RBCs have a central pallor that is what size of the RBC diameter?
A
> 1/3
23
Q
Are either anisocytosis or poikilocytosis seen in iron deficiency anemia?
A
Both can be seen
24
Q
Describe some of the findings of iron deficiency anemia on peripheral smear.
A
Hypochromic microcytosis;
anisocytosis (increased RDW);
poikilocytosis (elliptocytes, target cells, bizarre forms, etc.)
25
What is the number one cause of anemia within _hospitalized patients_?
Anemia of chronic disease
| (anemia of chronic inflammation)
26
What are the typical findings for RBC size in anemia of chronic disease?
Micro- or normocytic
27
Anemia of chronic disease is caused by increased levels of IL-\_\_\_, which leads to increased hepatic _________ synthesis, which leads to **decreased** **iron** release from **macrophages**.
Anemia of chronic disease is caused by increased levels of IL-**_6_**, which leads to increased hepatic **_hepcidin_** synthesis, which leads to **decreased** **iron** release from **macrophages**.
28
Name three acute phase reactants that are upregulated in anemia of chronic disease causing iron sequestration?
**IL-6**;
**hepcidin**;
**ferritin**
29
Compare the **MCV** for the following:
Iron deficiency anemia
Anemia of chronic disease
Compare the **MCV** for the following:
Iron deficiency anemia - **_decreased_**
Anemia of chronic disease - **_decreased or normal_**
30
Compare the **serum iron** for the following:
Iron deficiency anemia
Anemia of chronic disease
Compare the **serum iron** for the following:
Iron deficiency anemia --- **_decreased_**
Anemia of chronic disease --- **_decreased_**
31
Compare the **TIBC** for the following:
Iron deficiency anemia
Anemia of chronic disease
Compare the **TIBC** for the following:
Iron deficiency anemia --- **_increased_**
Anemia of chronic disease --- _**de****creased**_
32
Compare the **serum ferritin** for the following:
Iron deficiency anemia
Anemia of chronic disease
Compare the **serum ferritin** for the following:
Iron deficiency anemia --- **_decreased_**
Anemia of chronic disease --- **_increased_**
33
Compare the **marrow stores** for the following:
Iron deficiency anemia
Anemia of chronic disease
Compare the **marrow stores** for the following:
Iron deficiency anemia --- **_decreased_**
Anemia of chronic disease --- **_increased_**
34
_Iron deficiency anemia_
MCV: \_\_\_\_\_\_
Serum iron: \_\_\_\_\_\_
TIBC: \_\_\_\_\_\_
Serum ferritin: \_\_\_\_\_\_
Marrow stores: \_\_\_\_\_\_
_Iron deficiency anemia_
MCV: **_decreased_**
Serum iron: **_decreased_**
TIBC: **_increased_**
Serum ferritin: **_decreased_**
Marrow stores: **_decreased_**
35
_Anemia of chronic disease_
MCV: \_\_\_\_\_\_
Serum iron: \_\_\_\_\_\_
TIBC: \_\_\_\_\_\_
Serum ferritin: \_\_\_\_\_\_
Marrow stores: \_\_\_\_\_\_
_Anemia of chronic disease_
MCV: **_normal or decreased_**
Serum iron: **_decreased_**
TIBC: **_decreased_**
Serum ferritin: **_increased_**
Marrow stores: **_increased_**
36
The TIBC is basically a measure of what protein?
Transferrin
37
What term specifically refers to an anemia characterized by RBCs that are enlarged due to a defect in DNA synthesis?
Megaloblastic anemia
38
**True/False**.
Stress can lead to an elevation in MCV.
**True**.
Due to increased erythropoeisis --\> reticulocytosis.
(Reticulocytes are larger than erythrocytes.)
39
What are the two most common categories of **megaloblastic** anemia?
Nutritional (vitamin B9 or B12);
drug-induced
40
Name a few causes of non-megaloblastic macrocytic anemia.
Alcoholism;
stress;
liver disease;
hypothyroidism;
myelodysplastic syndromes
41
Name a few medications that can cause a megaloblastic macrocytic anemia.
Methotrexate;
hydroxyurea;
zidovudine
42
How do severe cobalamin and/or folate deficiencies appear on peripheral smear?
Elevated **MCV**;
**pancytopenia**;
low **reticulocyte** **count**;
**hypersegmented** neutrophils;
**hyperchromic** RBCs
43
Severe cobalamin and/or folate deficiencies result in \_\_\_\_\_\_cellular bone marrow.
Severe cobalamin and/or folate deficiencies result in **_hyper_**cellular bone marrow.
44
**True/False**.
Severe cobalamin and/or folate deficiencies result in hypercellular bone marrow and pancytopenia on peripheral smear.
True.
45
Pernicious anemia is characterized by antibodies against what?
**Intrinsic factor**
and/or
**parietal cells**
46
What term refers to the CNS damage seen in severe B12 deficiencies?
Subacute combined degeneration
47
B12 deficiencies are sometimes characterized by atrophic _________ and atrophic \_\_\_\_\_\_\_\_\_.
B12 deficiencies are sometimes characterized by atrophic **_gastritis_** and atrophic **_glossitis_**.
48
What serum substance is elevated in B12 deficiencies but not B9 deficiencies?
Methylmalonic acid
49
In which of the following will folate levels be low?
## Footnote
**B12 deficiency**
**Folate deficiency**
**B12 and folate deficiency**
**All three**!
(B12 is involved in folate synthesis.)
50
Serum ________ levels are increased in both B12 deficiency and folate deficiency.
Serum ________ levels are only increased in B12 deficiency (not folate).
Serum **_homocysteine_** levels are increased in both B12 deficiency and folate deficiency.
Serum **_methylmalonic acid_** levels are only increased in B12 deficiency (not folate).
51
Vitamin B12 is a cofactor for what two enzymes _only_?
(No others!)
**Methionine synthase** (homocysteine --\> methionine)
**Methylmalonyl-CoA mutase** (MM-CoA to succinyl-CoA)
52
What two cofactors are required for proper methionine synthase activity?
B12 _and_ folate
53
Besides producing methionine from homocysteine, what valuable product _necessary to DNA synthesis_ is produced by the reaction catalyzed by methionine synthase?
Tetrahydrofolate
54
**True/False**.
A lack of B12 and/or folate will result in decreased methionine synthase activity, leading to decreased production of tetrahydrofolate, leading to decreased DNA synthesis.
True.
55
Do B12 deficiencies and/or folate deficiencies lead to elevated serum homocysteine?
Do B12 deficiencies and/or folate deficiencies lead to elevated serum methylmalonic acid?
**Both**;
**B12 _only_**
56
What is the one major hematologic result of aplastic anemia?
Pancytopenia
57
\_\_\_\_% of cases of aplastic anemia are idiopathic.
**_65_**% of cases of aplastic anemia are idiopathic.
58
Most (65%) of cases of aplastic anemia are idiopathic.
Name a few drugs associated with this condition.
**C**loramphenicol;
**b**enzene;
certain **c**hemotherapeutic agents
(leading to a decreased **CBC**)
59
What are the two main pathophysiologies seen in aplastic anemia?
1. Autoimmune reaction against bone marrow progenitors
2. Primary stem cell defect
60
Can any infectious agents cause aplastic anemia?
Medical procedures?
Inherited conditions?
Some viral infections (e.g. non-A,B,C-type hepatitis);
whole body irradiation;
Fanconi's anemia
61
What is the underlying cause of Fanconi's anemia?
What is this disorder's inheritance pattern?
Defects in DNA repair;
autosomal recessive
62
What is the firstline treatment for aplastic anemia in patients under 50?
**Bone marrow transplant**
(immunosuppressives for older individuals)
63
Name the disease:
## Footnote
*a primary bone marrow disorder in which the erythroid progenitors are suppressed.*
Pure red cell aplasia
64
Pure red cell aplasia is associated with what malignancies?
What infectious agent(s)?
Exposure to what drug(s)?
Thymomas, LGL leukemias;
*parvovirus*;
erythropoeitin
65
What serum substances are generally elevated in cases of hemolytic anemia?
**LDH**;
**bilirubin** (indirect and total);
eventually, **EPO** as well
66
What serum substances are generally decreased in cases of hemolytic anemia?
**Haptoglobin**
| (binds hemoglobin)
67
What effect does hemolytic anemia generally have on each of the following?
H&H:
Serum total bilirubin:
Serum indirect bilirubin:
What effect does hemolytic anemia generally have on each of the following?
H&H: **_decreased_**
Serum total bilirubin: **_increased_**
Serum indirect bilirubin: **_increased_**
68
What effect does hemolytic anemia generally have on each of the following?
Serum haptoglobin:
Serum LDH:
Reticulocyte count:
What effect does hemolytic anemia generally have on each of the following?
Serum haptoglobin: **_decreased_**
Serum LDH: **_increased_**
Reticulocyte count: **_increased_**
69
The three main ways of classifying a hemolytic anemia:
1. __________ or \_\_\_\_\_\_\_\_\_\_
2. Intrinsic or extrinsic
3. Hereditary or acquired
The three main ways of classifying a hemolytic anemia:
1. **_Intravascular_** or **_extravascular_**
2. Intrinsic or extrinsic
3. Hereditary or acquired
70
The three main ways of classifying a hemolytic anemia:
1. Intravascular or extravascular
2. __________ or \_\_\_\_\_\_\_\_\_\_
3. Hereditary or acquired
The three main ways of classifying a hemolytic anemia:
1. Intravascular or extravascular
2. **_Intrinsic_** or **_extrinsic_**
3. Hereditary or acquired
71
The three main ways of classifying a hemolytic anemia:
1. Intravascular or extravascular
2. Intrinsic or extrinsic
3. __________ or \_\_\_\_\_\_\_\_\_\_
The three main ways of classifying a hemolytic anemia:
1. Intravascular or extravascular
2. Intrinsic or extrinsic
3. **_Hereditary_** or **_acquired_**
72
Where does **intravascular** hemolysis occur?
Within **circulation**
73
Where does **extravascular** hemolysis occur?
The **reticuloendothelial system**:
Macrophages within the liver, spleen, bone marrow, lymph nodes
74
**Schistocytes** are more closely related to what form of hemolytic anemia?
**Intravascular** hemolysis
75
**Microspherocytes** are more closely related to what form of hemolytic anemia?
**Extravascular** hemolysis
76
Elevated **bilirubin** is more closely related to what form of hemolytic anemia?
**Extravascular** hemolysis
77
Elevated **free** **hemoglobin** and **hemosiderinuria** are more closely related to what form of hemolytic anemia?
**Intravascular** hemolysis
78
**True/False**.
LDH is typically elevated and haptoglobin is typically decreased in both **intravascular** and **extravascular** hemolytic anemias.
**True**.
(Note: haptoglobin may be **normal** in extravascular hemolytic anemias.)
79
All hereditary hemolytic anemias are ___________ (intrinsic/extrinsic).
All hereditary hemolytic anemias are **_intrinsic_**.
80
**True/False**.
All intrinsic hemolytic anemias are hereditary.
**False**.
All ***hereditary*** hemolytic anemias are ***intrinsic*** to the RBC (but not all intrinsic HAs are inherited).
81
Name a few examples of **hereditary** hemolytic disorders.
*(Note: all hereditary hemolytic disorders are intrinsic to the RBC, so think about Hgb, membranes, enzymes, etc.)*
**Hgb**: Sickle cell, Hgb C, thalassemias
**Membranes**: Hereditary spherocytosis
**Enzymes**: G6PD deficiency, PK deficiency
82
Name a few examples of **hereditary** hemolytic disorders caused by defects in **hemoglobin**.
Sickle cell, Hgb C, thalassemias
83
Name an example **hereditary** hemolytic disorder caused by **membrane** defects.
Hereditary spherocytosis
84
Name a few examples of **hereditary** hemolytic disorders caused by **enzyme** **defects**.
**G6PD** deficiency
**Pyruvate** **kinase** deficiency
85
Is paroxysmal nocturnal hemoglobinuria extrinsic or intrinsic?
Is it hereditary or acquired?
**Intrinsic**,
## Footnote
**acquired**
86
Name a few general categories of the types of etiologies that might lead to acquired extrinsic hemolyses.
**Immune**;
**trauma** (e.g. MAHA);
**infection** (e.g. malaria);
**toxins** (e.g. lead)
87
What does it mean for a hemolytic anemia to be **intrinsic**?
The hemolysis occurs due to a defect in the RBC itself
(e.g. in its hemoglobin, membranes, or enzymes, etc.)
88
What does it mean for a hemolytic anemia to be **extrinsic**?
The hemolysis occurs due to a cause **external** to the **RBCs** themselves
(e.g. antibodies, infectious agents, trauma, complement, toxins, etc.)
89
Sickle cell anemia results due to what genetic defect?
Glutamate6 change to valine6 in _both β-hemoglobin chains_
90
**True/False.**
A single mutation in the gene coding for the sixth glutamic acid in β-hemoglobin is all it takes to result in sickle cell anemia.
**False**.
The disorder is autosomal recessive. A mutation in both genes (SS, homozygous) is necessary.
91
Sickle cell anemia results from a mutation in the __ glutamic acid in β-Hgb to \_\_\_\_\_\_\_\_.
Hemoglobin C disease results from a mutation in the __ glutamic acid in β-Hgb to \_\_\_\_\_\_\_\_.
6th, valine;
6th, lysine
92
**True/False.**
Sickle cell vasocclusive crises can affect any organ system.
True.
93
What inheritance pattern does sickle cell anemia follow?
Autosomal recessive
94
What is the first-line treatment for the disorder shown here?
Via what mechanism does it function?
Hydroxyurea;
increasing HgbF concetrations
95
HgbS is most likely to form fibers and sickle RBCs when it is in what state?
What are the implications?
The deoxygenated state;
hypoxic conditions (e.g. exercise, high altitudes) can exacerbate the condition
96
Through what mechanism does hydroxyurea improve the signs/symptoms of sickle cell anemia?
HgbF levels increase;
HgbF gets incorporated into HgbS chains and halts their continued polymerization
97
Is sickle cell anemia a hemolytic anemia?
Yes.
The sickle cells are rigid and inflexible and become jammed and/or lysed in capillary beds
98
Besides hydroxyurea, what other treatments exist for sickle cell anemia in certain situations?
Blood transfusions,
prophylactic antibiotics,
pain management,
bone marrow transplants
99
The glutamic acid that is changed to valine in sickle cell anemia is at what amino acid position and in which hemoglobin chain?
The glutamic acid that is changed to lysine in hemoglobin C disease is at what amino acid position and in which hemoglobin chain?
6, β-Hgb;
6, β-Hgb
100
What treatments are typically needed for hemoglobin C disease?
**None**;
it is basically a much less severe form of sickle cell anemia
(glutamic acid6 --\> lysine6 instead of valine)
101
What form of HbS (Sickle cell hemoglobin) is protective against malaria?
The heterozygous form
102
What are the three main types of hemoglobin found in adults?
In what percentages?
Adult Hb (HbA) **α2β2** \>95% of adult Hb
Adult Hb (HbA2) **α2δ2** \<3% of adult Hb
Fetal Hb (HbF) **α2γ2** \<3% of adult Hb
103
What are the two forms of adult hemoglobin?
HbA **α2β2** (\>95%)
HbA2 **α2δ2 **
104
**True/False.**
Individuals with sickle cell anemia are at an increased risk for infection.
True.
105
# Define thalassemia.
What inheritance pattern do thalassemias follow?
A mutation that diminishes or eliminates the production of one of the two chains of hemoglobin;
autosomal recessive
106
What population(s) is most affected by β-thalassemia?
What population(s) is most affected by α-thalassemia?
Mediterranean;
Southeast Asian, Middle Eastern, African
107
How are the hemoglobin genes controlled?
On what chromosome are the genes coding for α-globin located?
On what chromosome are the genes coding for β-globin located?
by **locus control regions**;
16;
11
108
In what order are the various β-globin genes organized on chromosome 11?
In the order in which they become useful
(starting with the locus control region; epsilon --\> gamma --\> delta --\> beta)
109
**True/False.**
Thalassemias can be caused by mutations in the coding or regulatory genes for α- or β-globin.
True.
110
What is β+-thalassemia?
Decreased β-hemoglobin production due to a mutation in the locus control region
111
In what order are the various α-globin genes organized on chromosome 16?
In the order in which they become useful
(starting with the locus control region; zeta --\> alpha)
112
A newborn presents in the first year of life with severe microcytic hypochromic anemia.
What autosomal recessive disorder might this child have and why are they at an increased risk of heart failure as early as the second or third decade of life?
β°-thalassemia major (Cooley's anemia)
buildup of iron in the heart and other organs
113
A symptomatic patient has both β-hemoglobin genes inactivated. What disorder is this?
An asymptomatic patient has a single β-hemoglobin genes inactivated. What disorder is this?
A symptomatic patient has a single β-hemoglobin genes inactivated. What disorder is this?
β°-thalassemia major (Cooley's anemia);
β-thalassemia minor;
β-thalassemia intermedia
114
What type of α-thalassemia is fatal in-utero and is characterized by virtually no α-globin production?
How many of the 4 α-globin genes (2 alleles each in 2 diploid cells) are deleted in this case?
α-thalassemia major *(hemoglobin Bart) (hydrops fetalis) (Hgb* γ4);
all 4
115
What type of heterozygous, severe α-thalassemia is characterized by only 25% of normal α-globin production?
How many of the 4 α-globin genes (2 alleles each in 2 diploid cells) are deleted in this case?
Hemoglobin H disease *(Hgb β4 + Hgb* γ4*)*
3
116
Both sickle cell anemia and thalassemias are protective against what?
Malaria
117
Is sickle cell anemia best described as a quantitative or qualitative hemoglobinopathy?
**Qualitative**
| (defective hemoglobin)
118
Are the thalassemias best described as quantitative or qualitative hemoglobinopathies?
**Quantiative**
| (reduced hemoglobin)
119
Name two tests used to **screen** for sickle cell anemia.
**Sickle solubility** test
**Metabisulfite** test
120
Name two tests used to confirm sickle cell anemia after screening tests (sickle solubility test, metabisulfite test).
Gel electrophoresis (HgbS)
High performance liquid chromatography
121
What is notable about the peripheral smear for a patient with HgbC disease?
'Boxcar' hemoglobin deposits
122
Describe the general perinatal changes in hemoglobin.
123
Thalassemias typically cause \_\_\_\_\_\_cytic \_\_\_\_\_chromic anemias.
Thalassemias typically cause **_micro_**cytic **_normo_**chromic anemias.
124
What are you likely to see on peripheral smear for thalassemias?
Microcytic, normochromic RBCs + target cells;
reticulocytosis
125
What would a CBC likely show for patients with thalassemia?
What RBC count?
MCV?
RDW?
**Elevated** RBC count
**decreased** MCV
**Normal-to-increased** RDW
126
What diagnostic test can be used in a patient with suspected hereditary spherocytosis?
The **osmotic** **fragility** test
(the cells rupture easily in hypotonic solution)
*(NOTE: a positive result is not specific to hereditary spherocytosis)*
127
What disorder is shown in the attached peripheral smear?
Hereditary elliptocytosis
128
G6PD deficiency is associated with __________ anemia due to hemolysis.
G6PD deficiency is associated with **_intermittent_** anemia due to hemolysis.
129
Pyruvate kinase deficiency is associated with __________ anemia due to hemolysis.
Pyruvate kinase deficiency is associated with **_continuous_** anemia due to hemolysis.
130
Which enzyme deficiency is associated with hemolytic anemia during times of oxidative stress?
G6PD deficiency
131
What is the role of glucose-6-phosphate dehydrogenase in the glycolysis pathway?
**NONE**.
This enzyme is part of the HMP.
132
Why does a G6PD deficiency result in hemolytic anemia?
**Decreased reduced glutathione** and **decreased NADPH** to buffer against oxidative damage
133
Why does a pyruvate kinase deficiency result in hemolytic anemia?
The lack of ATP results in **decreased Na/K pump activity** (leads to cell dehydration and lysis)
134
What is the inheritance pattern for G6PD deficiency?
X-linked recessive
135
Which is typically more severe, G6PD deficiency in Mediterranean populations or African populations?
**Mediterranean** populations
136
G6PD deficiency leads to an increase in oxidized Hgb, leading to formation of what?
Heinz bodies
137
Does G6PD deficiency cause intravascular or extravascular hemolysis?
Both
138
In patients with G6PD deficiency, the presence of Heinz bodies leads to slower RBC movement through the spleen, leading to what.
Bite cells
+
hemolysis
139
What can the following two tests be used to diagnose? (How do they work?)
**Ascorbate cyanide**
**Fluorescent spot**
G6PD deficiency
**Ascorbate cyanide** (highly oxidative)
**Fluorescent spot** (produced NADPH fluoresces)
140
**Paroxysmal nocturnal hemoglobinuria**:
Mutations in the ______ gene can lead to a decrease in synthesized ______ on RBC surfaces. This leads to decreased inhibition of complement and subsequent RBC hemolysis.
**Paroxysmal nocturnal hemoglobinuria**:
Mutations in the ***_PIG-A_*** gene can lead to a decrease in synthesized ***_PGI_*** on RBC surfaces. This leads to decreased inhibition of complement and subsequent RBC hemolysis.
141
Only \_\_\_\_\_% of cases of paroxysmal nocturnal hemoglobinuria are paryxosmal and nocturnal.
Only **_25_**% of cases of paroxysmal nocturnal hemoglobinuria are paryxosmal and nocturnal.
(Most cases just result in a *chronic anemia*.)
142
**True/False**.
Paroxysmal nocturnal hemoglobinuria is best described as a chronic anemia that has associations with leukopenia, thrombocytopenia, thrombosis, and even aplastic anemia, MDS, and AML.
True.
143
What is the best test for diagnosing paroxysmal nocturnal hemoglobinuria?
Flow cytometry
144
You run flow cytometry on a blood sample from a patient with paroxysmal nocturnal hemoglobinuria. What do you expect to see?
A deficiency of **CD55** and **CD59** on RBCs and neutrophils
145
What two surface markers are missing in paroxysmal nocturnal hemoglobinuria?
Decay-accelerating factor (DAF) (**CD55**);
membrane inhibitor of reactive lysis (MIRL) (**CD59**)
146
Autoimmune hemolytic anemias can be broken down into what two categories?
**_Warm_ antibody/agglutinin** HA
(or)
**_cold_ antibody/agglutinin** HA
147
IgG can bind to RBCs at ______ temperatures.
IgG can bind to RBCs at **_warm_** temperatures.
148
Warm agglutinins (\_\_\_\_\_ antibodies) typically bind to _____ on RBCs.
Warm agglutinins (**_IgG_** antibodies) typically bind to **_Rh factor_** on RBCs.
149
After warm agglutinins (IgG) bind RBC Rh factor, what happens next to result in hemolytic anemia?
**Macrophages** destroy the RBCs
| (via the Fc receptor)
150
What are some examples of diseases associated with autoimmune hemolysis mediated by warm agglutinins (IgG)?
Certain **infections** and **malignancies**;
**collagen** **vascular** disease
151
What are some examples of medications associated with autoimmune hemolysis mediated by warm agglutinins (IgG)?
**Penicillins, cephalosporins**
152
What test can be used to diagnose autoimmune hemolysis mediated by warm agglutinins?
**Direct Coombs**
(add antihuman anti-IgG antibodies to serum)
153
Name some of the characteristic cells you might see on peripheral smear of a person with autoimmune hemolysis mediated by warm agglutinins (IgG).
**Spherocytes**
+
**micro**spherocytes
154
IgM can bind to RBCs at ______ temperatures.
IgM can bind to RBCs at **_cold_** temperatures.
155
Cold agglutinins (\_\_\_\_\_ antibodies) typically bind to _____ on RBCs.
Cold agglutinins (**_IgM_** antibodies) typically bind to **_I (or i) antigen_** on RBCs.
156
After cold agglutinins (IgM) bind RBC I antigen, what happens next to result in hemolytic anemia?
**Phagocytes** (in the liver, spleen, and bone marrow) destroy the RBCs via **complement**-**mediated** **opsonization**
157
What are some examples of diseases associated with autoimmune hemolysis mediated by cold agglutinins (IgM)?
**B cell neoplasms**;
certain **infectious agents**
(e.g. *Mycoplasma pneumoniae*, EBV, CMV, HIV, etc.)
158
**Cold** agglutinins are Ig\_\_ that interact with __________ on RBCs.
**Warm** agglutinins are Ig\_\_ that interact with __________ on RBCs.
**Cold** agglutinins are Ig**_M_** that interact with **_I (or i) antigen_** on RBCs.
**Warm** agglutinins are Ig**_G_** that interact with **_Rh factor_** on RBCs.
159
Name some of the characteristics you might see on peripheral smear of a person with autoimmune hemolysis mediated by cold agglutinins (IgM).
Agglutination
160
What process is described below?
Pathological activation of the **clotting** **cascade** --\> **RBCs** **lysed** as they pass through the **fibrin** **strands**
Microangiopathic hemolytic anemia
| (MAHA)
161
Describe the process of microangiopathic hemolytic anemia:
Pathological activation of the ____________ --\> RBCs lysed as they pass through the \_\_\_\_\_\_\_\_\_\_\_.
Describe the process of microangiopathic hemolytic anemia:
Pathological activation of the _**clotting** **cascade**_ --\> RBCs lysed as they pass through the _**fibrin** **strands**_.
162
Name a few of the conditions associated with microangiopathic hemolytic anemia (MAHA). Add them to the list below:
\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_
pre-eclampsia
prosthetic heart valves
trauma
malignant hypertension
**TTP**
**HUS**
**DIC**
pre-eclampsia
prosthetic heart valves
trauma
malignant hypertension
163
Name a few of the conditions associated with microangiopathic hemolytic anemia (MAHA). Add them to the list below:
TTP
HUS
\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_
trauma
malignant hypertension
TTP
HUS
**DIC**
**pre-eclampsia**
**prosthetic heart valves**
trauma
malignant hypertension
164
Name a few of the conditions associated with microangiopathic hemolytic anemia (MAHA). Add them to the list below:
TTP
HUS
DIC
pre-eclampsia
\_\_\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_\_\_
TTP
HUS
DIC
pre-eclampsia
**prosthetic heart valves**
**trauma**
**malignant hypertension**
165
What will be seen on peripheral smear in patients with microangiopathic hemolytic anemia (MAHA) (e.g. due to TTP, DIC, HUS, pre-eclampsia, trauma, etc.)?
Schistocytes
166
What is shown in this peripheral smear?
Mararial infection
167
Does lead poisoning typically lead to acute or chronic anemia?
Chronic
168
**Lead** poisoning can lead to a deficiency of erythrocyte pyrimidine-specific, 5'-\_\_\_\_\_\_\_\_\_.
**Lead** poisoning can lead to a deficiency of erythrocyte pyrimidine-specific, 5'-**_nucleotidase_**.
169
What is seen on peripheral smear in a patient with lead poisoning?
Basophilic stippling
170
What is the probability that two random individuals are compatible for blood transfusion from one to the other?
~65%
171
What are the two most common blood types?
**O+** (38%)
**A+** (34%)
172
What is the universal RBC donor blood type?
O-
173
What are the universal plasma donor blood types?
**AB+**
and
**AB-**
174
Describe what you know about the frequency and features of different blood types.
175
What percentage of the world population is Rh+?
~85%
176
Are there many RBC antigens important to immunohematology?
Yes.
ABO and Rh + ~30 more
177
_Pre-Transfusion Testing:_
1. Positive ID on patient and sample
2. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
3. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
_Pre-Transfusion Testing:_
1. Positive ID on patient and sample
2. **ABO/Rh typing**
3. Check for **anti-RBC antibodies**
178
What should you order if you don't suspect a blood transfusion will be necessary for your patient (e.g. you're taking them into a routine surgery), but you would like the patient's blood bloodtyped and stored for later cross-matching in it becomes necessary?
Order a '**type and screen**'
179
What should you order if you suspect that a blood transfusion will be necessary for your patient, and you would like the following: the patient's blood to be bloodtyped and tested + compatible units of blood reserved for your patient.
Order a '**type and match**'
180
A 'type and \_\_\_\_\_\_\_' order is used for patients that may need transfusion, but it is not likely.
A 'type and \_\_\_\_\_\_\_' order is used for patients that have a higher likelihood of needing a transfusion.
A 'type and **_screen_**' order is used for patients that may need transfusion, but it is not likely.
A 'type and **_match_**' order is used for patients that have a higher likelihood of needing a transfusion.
181
How much blood comes in one donor unit?
500 mL
182
One unit of donor blood (~500 mL) is equivalent to what percentage of the average patient's blood volume?
12%
183
**True/False**.
Whole blood is rarely transfused today. Typically component therapy is used so as to only give the patient what they need and also to conserve resources.
True.
184
Passing out usually occurs after patients lose about what percentage of their blood volume?
~15%
185
What hematocrit does one unit of ADSOL blood have?
60%
186
Transfusing one unit of blood into a patient should increase their hemoglobin by ____ mg/dL and their hematocrit by \_\_\_\_%.
Transfusing one unit of blood into a patient should increase their hemoglobin by **_1**_ mg/dL and their hematocrit by _**3_**%.
187
On average, adequate oxygen-carrying capacity can be maintained by what minimum hemoglobin concentration?
And hematocrit?
*(Of course, age, degree/etiology of anemia, hemodynamic stability, and coexisting cardiovasculopulmonary conditions must be taken into account.)*
**7** g/dL
**21**%
188
Identify in which of the following scenarios is it appropriate to administer a red cell transfusion:
## Footnote
**Volume expansion**
**Iron replacement**
**To enhance wound healing**
**To enhance patient well-being**
Red cell transfusion is _not acceptable_ in any of these scenarios.
189
**True/False**.
While platelets have a long shelf-life, RBC units can only be stored for up to 5 days.
**False**.
While ***RBC units*** have a long shelf-life, ***platelets*** can only be stored for up to 5 days.
190
Why do platelet units for transfusion vary in volume from one to the next?
**Varying plasma levels**
*(different volumes collected even though the platelet number remains relatively constant --\> the platelets need to 'off-gas' H+, and, depending on a number of factors, certain amounts of plasma will be needed to keep the platelets functioning.)*
191
Why would you administer a platelet transfusion?
To reverse thrombocytopenia and/or platelet dysfunction
--\>
**to control bleeding**
192
**True/False**.
Platelets should be transfused when any patient's count has dropped below _20,000_/uL.
**False**.
Hospitalized, hemodynamically stable patients can remain clinically stable down to platelet counts as low as **5,000**/uL!
(Of course, if not stable and/or if showing oozing/bleeding or other symptoms, then you'll transfuse.)
193
A leukemia patient with a platelet count of 9,400/uL is presenting with oozing and bleeding. Your first platelet transfusion should be aiming to get their count up to what?
50,000/uL
194
1 __________ unit of platelets is derived from many donors and should raise the count by \_\_\_\_\_\_\_\_\_/uL.
1 __________ unit of platelets is derived from a single donor and should raise the count by \_\_\_\_\_\_\_\_\_/uL.
1 **_random_** unit of platelets is derived from many donors and should raise the count by **_5,000 - 10,000_**/uL.
1 **_apheresis_** unit of platelets is derived from a single donor and should raise the count by **_50,000_**/uL.
195
When should patients with ITP or TTP be administered platelet transfusions?
**_Only_** if life-threatening bleeding is present
196
What can fresh frozen plasma be used to provide a patient?
Clotting factors and inhibitors
| (will increase any factor by 3%)
197
Patients with what conditions would be best served by a transfusion of fresh frozen plasma?
**TTP** and **HUS**
**cirrhosis**;
also, inherited coagulation factor deficiencies;
reversal of severe warfarin effects
198
**True/False**.
Patients with less than 75% of normal clotting factors will begin to have bleeding issues.
**False**.
Patients with less than **_30_**% of normal clotting factors will begin to have bleeding issues.
199
Which transfusion unit type is larger, random or apheresis?
Apheresis
200
For what general type of condition should **red cell units** be administered?
_Severe_ anemia and/or hemorrhage
201
For what general type of condition should **fresh frozen plasma** units be administered?
_Severe_ clotting factor deficiency and/or _severe_ hemorrhage
202
For what general type of condition should **platelet units** be administered?
_Severe_ thrombocytopenia and/or life-threatening bleeding
203
For what general type of condition should **red cell units** be administered?
For what general type of condition should **fresh frozen plasma** units be administered?
For what general type of condition should **platelet units** be administered?
_Severe_ anemia and/or hemorrhage
_Severe_ clotting factor deficiency and/or _severe_ hemorrhage
_Severe_ thrombocytopenia and/or life-threatening bleeding
204
What transfusion unit is mostly used for replacing depleted fibrinogen?
Cryoprecipitate
205
What is cryoprecipitate?
**Plasma proteins** that were precipitated out of the plasma at cold temperatures
(e.g. clotting factors, especially **fibrinogen**)
206
What can be used in the surgical setting for stopping microbleeds in delicate locations where cautery or tying aren't viable options (e.g. the inner ear, the brain, the eye, etc.)?
**Fibrin glue**
(fibrinogen from cryoprecipitate mixed with bovine thrombin)
207
What clotting factor turns an immature, relatively soft clot into a mature, firm clot?
Factor XIII
208
What process allows for separating various blood components from one another (*e.g. red cells, plasma, platelets, fibrinogen, immunoglobulins, individual clotting factor types, albumin, granulocytes, Rhogam etc.*)?
Apheresis
209
What does it mean that transfusion products have undergone leuko-reduction?
All cellular immune cells are removed from the products
210
Name some reactions that can occur if WBCs are transfused in blood products.
Febrile non-hemolytic transfusion reaction;
transfusion-associated GVHD;
transfusion-related acute lung injury
211
**True/False**.
Transfusion carries the risk of some level of immunomodulation, such as HLA alloimmunization that can interfere with later transplants.
True.
212
How can transfusion-related GVHD be prevented?
**Irradiation** of blood components to be transfused
213
What is the mortality rate of **transfusion**-associated GVHD (typically only seen in immunocompromised patients)?
\> 90%
214
# FIll in the blanks for patients whose transfusion cellular products _must_ be irradiated:
The \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
For intra\_\_\_\_\_\_\_\_\_\_ transfusions
For ____________ exchange transfusions
For ____________ disease patients
# FIll in the blanks for patients whose transfusion cellular products _must_ be irradiated:
The **_immunocompromised_**
For intra**_uterine_** transfusions
For **_neonatal_** exchange transfusions
For **_Hodgkin's_** disease patients
215
Which types of blood transfusion products might need to be irradiated?
Only cellular products
| (RBCs, platelets, whole blood, etc.)
