Exam 2 Flashcards
1
Q
Hematopoietic growth factors
A
Hormones that regulate the proliferation and differentiation of hematopoietic stem cells
2
Q
Important growth factors
A
Stem cell factor and FLT3
3
Q
Effect of deficiency of growth factors
A
Leads to aplastic anemia
4
Q
Effect of overactivity of growth factors
A
Leads to leukemia
5
Q
WBC Count
A
4-11 x 10^9/L
6
Q
Leukocytosis
A
Increased WBC count above normal range
7
Q
Leukopenia
A
Decreased WBC count below normal range
8
Q
Neutrophils Differential Count %
A
50-70
9
Q
Neutrophils Absolute Count
A
1500-6500
10
Q
Lymphocyte Differential Count %
A
20-44
11
Q
Lymphocyte Absolute Count
A
1200-3400
12
Q
Monocyte Differential Count %
A
2-9
13
Q
Monocyte Absolute Count
A
100-600
14
Q
Bands Differential Count %
A
0-6
15
Q
Bands Absolute Count
A
0-700
16
Q
Eosinophils Differential Count %
A
0-5
17
Q
Eosinophils Absolute Count
A
0-500
18
Q
Basophils Differential Count %
A
0-2
19
Q
Basophils Absolute Count
A
0-200
20
Q
Relative cytosis or cytopenia
A
% is out of range (absolute count normal)
21
Q
Absolute cytosis or cytopenia
A
absolute count is out of range (better reflection of health)
22
Q
Automated WBC differential
A
instrument analyzes 10,000 cells and sorts them by size and granularity
23
Q
Manual WBC differential
A
tech counts 100 cells on peripheral smear
24
Q
Neutrophils
A
Phagocytic cell containing a nucleus with 2-5 lobes and pink cytoplasmic granules, Short-lived (6 days) and highly motile
25
Chemotaxis
Migration toward sites of infection or inflammation
26
Neutrophilia
increase in neutrophils
27
Leukomoid Reaction
an increase in white blood cell count, which can mimic leukemia
28
Left shift
increased numbers of less mature cells (precursors) released from the bone marrow to the peripheral blood
29
Leukocytosis is common with?
severe or chronic infection, severe hemolysis and metastatic cancers
30
Leukocytosis is associtated with?
toxic granulation (increased granulation
vacuolation (due to phagocytosed microbes)
dohle bodies (pale round to linear blue aggregates of rough endoplasmic reticulum)
31
Neutropenia
decrease in neutrophils
32
Selective Neutropenia Congenital Causes
Kostmann syndrome
Bening neutropenia
Cyclical neutropenia
33
Acquired Selective Neutropenia
Drug induced
Autoimmune (SLE)
Viral Infection
Some bacterial infections (Typhoid)
34
Pancytopenia
a decrease in all blood cells (RBCs, WBCs, and platelets)
35
Reactive Lymphocytes Features
increased cell size
increased cytoplasm
radial blueing
invagination around red cellS
seen most commonly with viral infections (especially EBV)
36
Lymphocytosis
increase in lymphocytes
37
Causes of Lymphocytosis
viral infection
some bacterial infection (Pertussis)
Other (Allergic drug interactions, splenectomy, metastatic carcinoma)
Chronic Lymphocytic Leukemia (CLL)
Other Lymphomas
38
Cause of Lymphocytopenia
bacterial or fungal sepsis
post-operative state
post steroid therapy
immunodeficiency
autoimmune disorders
39
Effect of Steroid Therapy on Lymphocytes
Lymphoma, because steroid melts the lymphocytes, hence it is part of all chemotherapy regiments in lymphoma
40
Monocytes
Large phagocytic cells with indented nucleus and fine cytoplasmic granules, Matures into different types of macrophages at different anatomical locations
41
Cause of Monocytosis
chronic infection
autoimmune disease
chronic neutropenia
acute leukemia
chronic myelomonocytic leukemia
42
Cause of Monocytopenia
Hairy cell leukemia
43
Major Functions of Eosinophils
anti-parasitic and bactericidal activity
immediate allergic reactions
modulating inflammatory responses
44
Causes of Eosinophilia
allergy and asthma
parasite infection
connective tissue disease
leukemia/lymphoma (eosinophilic leukemia, CML, AML M4)
idiopathic
45
Major Functions of Basophils
immediate allergic reaction
anticoagulant activity
vasodilation
46
Causes of Basophilia
leukemia (CML)
hypothyroidism
some viral infections
inflammatory conditions
drugs
hyperlipidemia
47
Leukoerythroblastic Picture
bone marrow response in which nucleated RBCs and immature WBCs are released into the peripheral blood
48
Cause of Leukoerythroblastic Picture
severe infection
severe hemolysis (thalassemia major)
primary myelofibrosis
metastatic tumors
49
Wright Stain
primary stain used on aspirate smears
combination of acid dye (eosin) and basic dye (methylene blue)
50
What does acid dye (eosin) stain?
erythrocytes and cytoplasmic granules
51
What does basic dye (methylene blue) stain?
nuclei and cytoplasmic granules
52
Prussian Blue Iron
second most common stain used on aspirate smear, aspirate clot
used to evaluate iron stores, sideroblasts and ringed sideroblasts
53
Iron Stores
macrophages store iron and return them to RBC
54
Sideroblasts
RBC incorporated iron into hemoglobin
usually 20-60% of RBCs
55
Ringed Sideroblasts
Iron accumulates in mitochondria of RBCs with disordered hemoglobin synthesis
56
Myeloperoxidase
stain performed on PB or aspirate smear
used in acute leukemias to confirm myeloid lineage
57
Sudan Black B
stain performed on PB or aspirate smear
used in acute leukemias to confirm myeloid lineage
58
Butyrate Esterase
stain performed on PB or aspirate smear
used in acute leukemia to distinguish neutrophilic and monocytic lineages
59
Chloroacetate Esterase
stain performed on PB or aspirate smear
used in acute leukemias to distinguish neutrophilic and monocytic lineages
60
Periodic Acid Schiff (PAS)
stain performed on aspirate smear
used in the diagnosis and typing of acute leukemias
61
the appearance of cells in PAS
normal: fine diffuse of granules
abnormal: coarse granules in acute myeloid leukemia M6
62
the appearance of cells in sudan black b
brown/black precipitate in the cytoplasm, color intensity increases with the maturity of the cell
63
the appearance of cells in butyrate esterase
brown pigment in monocytes
64
the appearance of cells in chloroacetate esterase
blue pigment in neutrophils
65
Terminal deoxynucleotidyl transferase (TdT)
various methods of detection (flow cytometry, immunofluorescent stain, immunohistochemical stain)
DNA polymerase enzyme adds nucleotides to 3' terminus of DNA molecule
positive in ALL and some AML
66
Acquired Abnormality of B12 or Folate Deficiency
Causes hypersegmented neutrophils (>6 lobes)
67
Acquired Abnormality of Drug/toxin effect
dysplasia-like changes with hypogranular cytoplasm or hypolobated nuclei
68
Pelger-Huet Anomaly
Congenital
hyposegmented neutrophils with bilobed "prince nez" or monolobated nuclei
normal cytoplasm
normal function
other white cells, red cells and platelets normal
69
Pelger Huet anomaly vs Pseudo-Pelger-Huet anomaly
Pelger-Huet anomaly: inheritable (autosomal dominant) abnormality of nuclear segmentation, cells have a mature nucleus, and mature cytoplasm but it is a congenital condition. Also, there is no loss of cellular function.
Pseudo-Pelger Huet: Cells have a nucleus and are often hypo granular but it is an acquired condition. This is seen in underlying disorders, like myelodysplasia or myeloproliferative diseases.
70
May-Hegglin Anomaly
decreased WBC count
all WBC have dohle bodies, blue-gray inclusions comprised of RNA, located anywhere in cytoplasm
normal function
RBC count normal
Platelet count mildly decreased (mostly large and giant platelets)
71
Alder-Reilly Anomaly
normal WBC count
all WBC with large purple cytoplasmic inclusions
disorder polysaccharide metabolism and lysosomal accumulation of mucopolysaccharide
normal function
RBC and platelet count normal
72
Features of Mucopolysaccharide disorders
abnormal face, skeletal dysplasia and mental retardation
73
Chediak-Higashi Anomaly
decreased WBC count
all WBC have giant granules, representing fused lysosomes
function is abnormal
RBC and platelet count normal/decreased
74
Gaucher's Disease
enzyme deficiency of beta-glucocerebrosidase
accumulation of glucocerebroside
macrophage with abundant fibrillar cytoplasm (wrinkled tissue paper)
75
Niemann-Pick Disease
enzyme deficiency of sphinogomyelinase
accumulation of sphigomyelin
macrophages with foamy cytoplasm and small uniform vacuoles
76
Bone marrow cellularity of Myelodysplastic Syndromes (MDS)
hypercellular, would have dysplasia in one or more lineages
77
peripheral cytopenias of MDS
pancytopenia (anemia, leukopenia, and thrombocytopenia )
78
Erythropoietic changes in the bone marrow of MDS
megaloblastic nuclei, asymmetrical nuclear budding, and increased ring sideroblasts
79
Platelet changes of MDS
giant or hypo-granular platelets in peripheral blood, also small megakaryocytes with non-lobated, hypolobated, or disjointed nuclei
80
neutrophilic changes of MDS
hyposegemented nuclei or hypersegmented nuclei, or hypo-granular cytoplasm
81
Auer rods
red, round, or rod-shaped cytoplasmic inclusions
usually present in immature granulocytes and are uncommon in immature monocytes or more mature cells.
82
Indication of Auer rods
acute nonlymphocytic leukemia.
83
Chronic Myeloid Leukemia (CML) Epidemiology
most common MPN
accounts for 15-20 of all leukemias
median age at diagnosis is 40-50%
84
CML Clinical Presentation
asymptomatic in 20-40%
routine CBC: marked leukocytosis
common symptoms: fatigue, weight loss, night sweats
splenomegaly
85
CML Main Differential Diagnosis
leukemoid reaction
other MPN or MDS/MPN
86
CML vs Leukemoid Reaction
Differential in CML: Bands, Metamyelocytes, Myelocytes
Differential in Leukemoid: Mainly Bands
Morphology in CML: Normal
morphology in Leukemoid: Toxic
87
General Feature of Myeloproliferative Neoplasm
Cytosis – increased number of cells
Organomegaly (enlargement of organs, in particular, splenomegaly)
Hypercellular bone marrow
May progress to acute leukemia
88
Myeloproliferative Neoplasm (MPN)
group of diseases in which the bone marrow makes too many RBCs, WBCs, or platelet
89
peripheral blood abnormalities of MPN
cytosis (erythrocytosis, granulocytosis, and thrombocytosis)
90
bone marrow changes of MPN
panhypercellularity (abnormal excess of all cells in bone marrow)
91
Leukocyte Alkaline Phosphatase (LAP)
stain performed only on PB
estimates the amount of alkaline phosphatase enzyme in each cell, used to diagnose chronic myeloid leukemia
92
the appearance of cells in LAP
hydrolase enzyme that removes phosphate groups from molecyles
when you have chronic myeloid leukemia (CML), you have less alkaline phosphatase in your white blood cells than normal
intensity varies with concentration of enzyme un the cell
93
Features of CML chronic phase
Leukocytosis
mainly neutrophils and myelocytes
blasts <10% and basophils <20%
stable course for years
94
Peripheral Blood Features of CML Chronic Phase
WBC: leukocytosis due mainly to neutrophils
myeloid cells in all stages of maturation
usually less than 2% blasts
absolute basophilia and eosinophilia
RBC: mild anemia
Platelets: normal or increased
95
Bone Marrow Features of CML Chronic Phase
hypercellular with myeloid hyperplasia
less than 10% blasts
micromegakaryocytes
pseudo-Gaucher cells and sea blue histocytes
96
Characteristic of CML Accelerated Phase
10-19% blasts in blood or bone marrow
>20% basophils in blood
Persistent thrombocytopenia <100,000 unrelated to therapy
Persistent thrombocytosis >1,000,000 despite adequate therapy
Increasing WBC count and spleen size
Cytogenetic evidence of clonal evolution
97
Characteristics of CML Blast Phase
>20% blasts in blood or bone marrow
Extramedullary proliferation of blasts
Blast lineage may be myeloid (80%) or lymphoid (20%)
Resembles acute leukemia
98
CML Prognosis
survival with treatment (5 years overall survival >90%)
first-line therapy: tyrosine kinase inhibitors like imatinib (Gleeven)
second-line therapy: stem cell transplantation
99
CML Cytogenetics
required for diagnosis of CML
t(9;22) + BCR-ABL translocation = Philadelphia chromosome
BCR-ABL hybrid gene has tyrosine kinase activity and enhanced phosphorylating activity resulting in altered cell growth and uncontrolled proliferation
100
Polycythemia vera (PV) Epidemiology
median age at diagnosis is 60yrs
slight male predominance
101
PV Clinical Presentation
Routine CBC: increased hemoglobin or red cell mass
Increased blood viscosity (hypertension, headache, dizziness)
Thrombosis (deep vein thrombosis, heart attack, stroke)
Redness in face or palms
Pruritis (itching)
Splenomegaly (70%) and hepatomegaly (40%)
102
PV Main Differential Diagnosis
Secondary polycythemia
Other MPN or MDS/MPN
103
PV Polycthemic Stage Peripheral Blood Changes
WBC: normal or increased
RBC:
Hgb >18.5 g/dl in men
Hgb >16.5 g/dl in women
Elevated RBC mass >25% above mean normal predicted value
Normochromic normocytic red cells
Low serum erythropoietin level
Platelets: normal or increased
104
PV Polycythemic Stage Bone Marrow Changes
Hypercellular with erythroid hyperplasia
Small and giant megakaryocytes with deeply lobulated nuclei
Absent iron stores
105
PV Spent Phase PB changes
anemia
leukoerythroblastic picture
anisopoikilocytosis with tear drops
106
PV Spent Phase Bone Marrow Changes
ofter hypocellular
marked reticulin and collagen fibrosis
107
PV Cytogenetics
no specific genetic defect
95% have JAK2 mutation
20% also have +8, +9, del(20q), del(13q) or del(9p)
108
PV Prognosis
Without therapy, median survival is few months
Most patients die from thrombosis or hemorrhage
10% will develop MDS or AML
With current therapy, median survival is 10-15 yrs
First line therapy: Phlebotomy + aspirin
Second line therapy: Phlebotomy + aspirin + myelosuppressive drug (hydroxyurea)
109
Essential Thrombocythemia (ET) Epidemiology
median age at diagnosis is 50-60yrs
110
ET Clinical Presentation
Asymptomatic in 50%
Routine CBC: Increased platelet count
Thrombosis or hemorrhage
Common symptoms: fatigue, weight loss
Mild splenomegaly (50%) and hepatomegaly (20%)
111
ET Main Differential Diagnosis
Reactive thrombocytosis (iron deficiency, splenectomy, surgery, infection, autoimmune disease)
Other MPN or MDS/MPN
112
ET Peripheral Blood Changes
WBC: normal
RBC: normal
Platelet:
Platelet count >450,000/ul
Anisocytosis (tiny and giant platelets)
113
ET Bone Marrow Changes
Hypercellular with megakaryocytic hyperplasia
Many large to giant megakaryocytes with abundant mature cytoplasm and hyperlobulated nuclei
Minimal reticulin fibrosis, no collagen fibrosis
Iron stores present
114
ET Cytogenetics
No specific genetic defect
Chromosomes usually normal
60% have JAK2 mutation
115
ET Prognosis
Long survival with near normal life expectancy
Less than 5% will develop MDS or AML
Main therapy: Aspirin with or without hydroxyurea
116
Primary Myelofibrosis (PMF) Epidemiology
median age at diagnosis is 50-60 yrs
117
PMF Clinical Presentation
Asymptomatic in 30%
Routine CBC: Increased WBC and platelet count
Common symptoms: fatigue, weight loss, night sweats
Massive splenomegaly
118
PMF Main Differential Diagnosis
other MPN or MDS/MPN
119
PMF Prefibrotic Stage PB changes
WBC: mild to mod leukocytosis
RBC: mild to mod anemia
Platelets: mild to mod thrombocytosis
120
PMF Prefibrotic Stage BM changes
Hypercellular with myeloid and megakaryocytic hyperplasia
Mostly large megakaryocytes with balloon-shaped nuclei, abnormal chromatin clumping, and decreased amounts of cytoplasm
Minimal fibrosis
121
PMF Fibrotic Stage PB Changes
WBC: usually decreased, left-shifted
RBC: mod to marked anemia, marked anisopoikilocytosis with tear drops, nucleated RBC
Platelets: usually decreased, anisocytosis, circulating megakaryocytic nuclei
122
PMF Fibrotic Stage BM Changes
Often hypocellular
Patches of hematopoietic cells separated by loose connective tissue or fat
Prominent clusters of abnormal megakaryocytes
Markedly increased reticulin and collagen fibrosis
Osteosclerosis (new bone formation)
123
PMF Cytogenetics
no specific genetic defect, common chromosomal abnormalities (del(13q), del(20q), der(6)t(1;6), 50% have JAK2 mutation
124
PMF Prognosis
median survival time is 3-7yrs from fibrotic stage, 10-20% develop AML
125
JAK2 Mutation
Non receptor protein tyrosine kinase involved in signal transduction pathway
Point mutation lead to loss of auto-inhibitory control
Mutated JAK2 is in a constitutively active state
126
JAK2 Mutation Progression
Mutation -> activation of transcriptional factors ->
increased proliferation and decreased apoptosis ->
127
JAK2 Mutation Results
PV (95%)
ET (60%)
PMF (50%)
128
Myelodysplasia
Dysplasia = abnormal morphology
May be present in one or more myeloid lineages
Seen in various conditions
129
WBC Dysplasia
most evident in peripheral blood neutrophils
hypo-segmented nuclei
hyper-segmented nuclei
hypogranular cytoplasm
130
RBC Dysplasia
need to assess erythroid precursors in bone marrow
megaloblastic nuclei
asymmetrical nuclear budding
131
Myelodysplastic Syndrome (MDS)
clonal hematopoietic stem cell disorders with abnormal maturation and ineffective hematopoiesis (cells produced in marrow but never enter circulation)
132
Clinical Presentation of MDS
mean age at diagnosis 70yrs
peripheral cytopenia, most commonly macrocytic anemia
fatigue
no gematosplenomegaly
133
MDS PB Changes
Pancytopenia
134
MDS Bone Marrow Changes
hypercellular
dysplasia in one or more lineages
135
MDS Cytogenetics
common chromosomal abnormalities: 5-, +7, +8
136
MDS Prognosis
progression to AML ranges from 5% in MDS-SLD to 33% with MDS-EB-2
treatments includes supportive (blood products, transfusions) and chemotherapy
137
Chronic Myelomonocytic Leukemia (CMML) Epidemiology
median age at diagnosis is 65-75 yrs old
138
Clinical Presentation of CMML
fatigue, weight loss, night sweats
splenomegaly
history of frequent infections
bleeding
139
CMML-1
<5% blasts in PB and <10% in BM
140
CMML-2
5-19% blasts in PB or 10-19% blasts in BM or 20% blasts plus Auer rods
141
CMML Cytogenetics
no specific genetic defect
common chromosomal abnormalities: +7, +8, abnormal 12p
142
CMML PB Changes
WBC: usually increased
Neutrophilia
Monocytosis (>10% WBCs, abs mono count >1 x 10^9/L)
RBC: mild anemia, normocytic or macrocytic
Platelets: mild to mod decreased
143
CMML BM Changes
Usually hypercellular
Proliferation of granulocytes and monocytes
Dysplastic maturation seen in all lineages
144
Myelodysplastic Syndrome vs Acute Leukemia
The diagnosis of MDS includes a maximum number of blasts at 19% whereas for the diagnosis of AML the minimum criterion is at least 20% blasts. The distinction between the two is based on the blast percentage. Also, there is a possibility of MDS progressing to AML, ranging from 5% in MDS-SLD to 33% with MDS-EB-2. Acute leukemia: proliferation is in precursors with reduced capacity to differentiate into mature cells. MDS is a type of chronic leukemia where proliferation is mainly in mature cells.
145
Refractory Anemias
refers to red blood cells showing dysplasia in the bone marrow. A person with this type of MDS will also have low numbers of RBCs but a normal number of WBCs and platelets. Also, there is a normal number of blasts in the bone marrow, and <15% of ringed sideroblasts
