HEMATOLOGY Flashcards
(199 cards)
1
Q
Internal causes of posthemorrhagic anemia (4)
A
- GI bleeding
- Rupture of spleen
- Rupture of an ectopic pregnancy
- Subarachnoid hemorrhage
2
Q
Dominant feature of the 1st clinical/pathophysiological stage after blood loss
A
Hypovolemia
3
Q
Major threats of the 1st clinical/pathophysiological stage after blood loss (2)
A
- Loss of consciousness
* Acute renal failure
4
Q
Dominant feature of the 2nd clinical/pathophysiological stage after blood loss
A
Anemia (due to hemodilution)
5
Q
If 3 days after acute blood loss, hemoglobin is at 7 g/dL, how many percent of the blood has been lost?
A
About 50%
6
Q
Dominant feature of the 3rd clinical/pathophysiological stage after blood loss
A
Elevated reticulocyte count and EPO levels
7
Q
The most frequent neoplastic disease in children
A
ALL
8
Q
Peak age of ALL
A
3–4 years of age
9
Q
Congenital chromosomal abnormality that have a twentyfold increased incidence of leukemia
A
Down syndrome
10
Q
The etiological agent for adult T-cell leukemia/ lymphoma
A
Human T-cell leukemia virus I (HTLV-I)
An aggressive adult T-cell leukemia
11
Q
Etiologic agent of an endemic African type of Burkitt’s lymphoma
A
Epstein-Barr virus
12
Q
The major criteria to subdivide ALL into B-cell lineage or T-cell lineage (T-ALL) leukemias
A
Immunological markers
13
Q
Major aim of classification of acute leukemia
A
to distinguish between AML and ALL
Different treatment approaches and drug sensitivities
14
Q
to distinguish between AML and ALL
Different treatment approaches and drug sensitivities
A
Acute leukemia (ALL)
15
Q
Biopsy of the bone marrow demonstrate marked hypercellularity with replacement of fat spaces and normal elements by infiltration with leukemic cells
A
ALL
16
Q
An essential routine diagnostic measure for ALL to rule out CNS leukemia
A
Lumbar puncture
17
Q
Lumbar puncture is restricted to leukemic patients with (3)
A
- Adequate platelet count (>20 × 109/L)
- Absence of manifest clinical hemorrhage
- Without a high white blood cell count
18
Q
This should be given to all at the first lumbar puncture in leukemic patients
A
Intrathecal methotrexate
19
Q
French-American-British classification morphology of ALL that has clinical and prognostic relevance
A
L3 morphology
L1 and L2 - no clinical consequence
20
Q
French-American-British classification morphology of ALL that is indicative of mature B-ALL (aka Burkitt’s leukemia)
A
L3 morphology
21
Q
Positive marker in leukemia is considered if ____ of the cells are stained with the monoclonal antibody
A
> 20%
22
Q
Which is more common? B cell ALL or T cell ALL?
A
B cell
More than 70% of adult ALLs
23
Q
The most frequent immunological subtype of ALL
A
Common ALL
24
Q
ALL antigen
A
gp100/CD10 – a glycoprotein
25
ALL subtype that is characterized by the expression of cytoplasmic immunoglobulin
Pre-B-ALL (early B-ALL)
26
Also termed early B-precursor ALL
Pro-B-ALL
27
A leukemia that was formerly termed non-T, non-B-ALL, or null-ALL
Pro-B-ALL
Neither T-cell nor B-cell features could be demonstrated
28
Markers of Pro-B-ALL (2)
1. Tdt (terminal) deoxynucleotidyl transferase
| 2. CD19
29
All T Cell lineage ALL has these antigens (2)
1. T-cell antigen (gp40, CD7)
| 2. Cytoplasmatic or surface CD3
30
Leukemia wherein markers of lymphoid and myeloid lineages are co-expressed on the same leukemic cells
Biphenotypic or Mixed Leukemias
Without the typical phenotype of either ALL or AML
31
Newly defined ALL entities with poor prognosis (2)
1. Ph-like ALL
| 2. Early T-precursor ALL
32
Dasatinib is a
BCR-ABL inhibitors
33
Ruxolitinib is a
JAK2 inhibitors
34
Detection of residual leukemic cells, not recognizable by light microscopy
Minimal Residual Disease
35
Methods for determining MRD (3)
1. Flow cytometry
2. RT-PCR
3. Detection of fusion genes associated with chromosomal abnormalities
36
T or F. Molecular response can be evaluated only for patients in complete cytological remission from ALL
True
37
The most relevant independent prognostic factor for disease-free survival and overall survival from ALL
Molecular complete response/molecular remission
38
Prognostic parameters of ALL (4)
1. Age
2. White blood cell count
3. Specific immunophenotypes
4. Cytogenetic and genetic aberrations
39
Standard-risk patients of ALL is defined as _____.
without any poor-risk factors
With a good chance of cure by chemotherapy
40
High-risk patients of ALL is defined as _____.
with one or more of poor risk factors
Most often candidates for a stem cell transplant in first complete remission
41
Outcome of ALL is strictly related to (2)
1. Age of the patient
| 2. Treatment protocols
42
Maintenance therapy for ALL (3) and duration
1. 6-Mercaptopurine
2. Methotrexate
3. TKI (Ph-positive ALL)
Duration: 2 – 2.5 years
43
Without some form of prophylactic CNS-directed therapy, around ___ of adults with ALL developed CNS leukemia
30%
44
Tyrosine kinase inhibitors that cross the BBB (2)
Dasatinib and ponatinib
Imatinib and nilotinib – do not cross the BBB
45
The most promising option to achieve a remission of CNS leukemia
Allogeneic stem cell transplantation
46
T or F. Sibling donors is much more preferred than unrelated donors in stem cell transplantation
False. There is a shift from sibling donors to matched unrelated donors or haploidentical transplants from relatives
47
Indications for stem cell transplantation in first remission:
1. Persistent MRD
| 2. All high-risk patients either defined by conventional clinical prognostic factors or by MRD positivity
48
Autologous stem cell transplantation in first remission of ALL is restricted to these patients (3)
1. Ph+ ALL
2. MRD negative
3. Older patients
49
The only curative option for all relapsed adult ALL patients
Allogeneic stem cell transplant
Recommended to all patients in second or later complete remission
50
1st generation TKI
Imatinib
51
2nd generation TKI
Dasatinib, nilotinib
52
3rd generation TKI
Ponatinib
53
Anti CD20 used in immunotherapy of ALL
Rituximab
54
Anti CD22 used in immunotherapy of ALL (2)
1. Inotuzumab ozogamicin
| 2. Epratuzumab
55
Anti CD19 and CD3 used in immunotherapy of ALL
Blinatumomab
56
Leukemic cells not detectable by light microscopy (<5% blast cells in bone marrow)
Complete (hematologic) remission
57
Patient in complete remission, MRD not detectable, ≤0.01% = ≤1 leukemia blast cell in 10,000
Complete molecular remission MRD-negativity
58
Patient in complete hematologic remission but not in molecular complete remission >0.01%
Molecular failure/ MRD-positivity
59
Patient still in complete remission had prior molecular complete remission. Leukemic blast cells detectable in bone marrow not detectable (<5%)
Molecular relapse/ MRD-positivity
60
>5% ALL cells in bone marrow/blood after chemotherapy
Hematologic relapse
61
Targeted therapy for Ph/BCR-ABL+ ALL
TKIs
Imatinib, Dasatinib, Nilotinib, Bosutinib, Ponatinib
62
Targeted therapy for Ph-/BCR-ABL-like ALL
Dasatinib and Ruxolitinib
63
Most common form of anemia
hypoproliferative anemia
64
reticulocyte index in hypoproliferative anemia
<2-2.5
65
Most common form of hypoproliferative anemia
iron deficiency anemia
66
Normochromic, normocytic anemias (6)
1. early stage of IDA
2. anemia of acute and chronic inflammation
3. renal disease
4. protein malnutrition
5. endocrine deficiencies
6. marrow damage
67
Transferrin that has the highest affinity for transferrin receptors
diferric transferrin
68
Storage protein to which excess iron binds
apoferritin
forms ferritin
69
average life span of RBC and the turn over rate per day
120 days
0.8-1.0%
70
Amount of iron needed to replace the RBCs lost through senescence
20 mg/day
71
Amount of dietary iron requirement per day (for men and women)
men - 10% of body iron content/year = 1 mg elemental iron daily
female of childbearing age - ~15% of body iron content/year = 1.4 mg elemental iron daily
72
During the last 2 trimesters of pregnancy, the daily iron requirements increase to
5-6 mg
73
Primary site of iron absorption
proximal small intestine
74
principal iron regulatory hormone that regulates the ferroportin transporter
hepcidin
low in IDA in order to facilitate increase absorption
75
Stages of iron deficiency (3)
1. negative iron balance
2. iron-deficient erythropoiesis
4. IDA
76
```
Laboratory finding in the first stage of iron deficiency in terms of:
serum ferritin
stainable iron on BMA
serum iron
TIBC
red cell protorphyrin
RBC morphology and indices
```
low :
serum ferritin
stainable iron on BMA
normal:
serum iron
TIBC
red cell protorphyrin
normochromic normocytic
77
```
Laboratory finding in the 2nd stage of iron deficiency in terms of:
serum ferritin
stainable iron on BMA
serum iron
TIBC
red cell protorphyrin
TSAT
RBC morphology and indices
```
```
serum ferritin - decreased
stainable iron on BMA - decreased
serum iron - decreased
TIBC - increased
red cell protorphyrin - increased
TSAT -decrease to 15-20%
RBC morphology and indices - microcytic, hypochromic
```
78
Laboratory finding in IDA in terms of: TSAT
Decreased TSAT to 10-15%
79
Normal values for:
```
Marrow iron stores
serum ferritin
TIBC
Serum iron
TSAT
marrow sideroblasts
RBC protoporphyrin
```
```
Marrow iron stores: 1-3+
serum ferritin: 50-200 ug/L
TIBC: 300-360 ug/dL
Serum iron: 50-150 ug/dL
TSAT: 30-50%
marrow sideroblasts: 40-60%
RBC protoporphyrin: 30-50 ug/dL
```
80
T or F. Erythropoietin therapy may cause iron deficiency
True. increase demand for iron
81
IDA in adult male means
GI loss unti proven otherwise
82
Signs of advanced tissue Fe deficiency (2)
koilonychia
| cheilosis
83
fissures at corner of the mouth seen in IDA
cheilosis
84
spooning of fingernails seen in IDA
koilonychia
85
represents amount of circulating iron bound on transferrin
serum iron
86
indirect measure of the circulating transferrin
TIBC
87
Transferrin saturation or TSAT is calculated by
serum iron x 100/TIBC
88
ferritin accumulating in the RE cells and is less readily available source of iron
hemosiderin
89
the most convenient laboratory test to estimate iron stores
serum ferritin levels
better indicator of iron overload than marrow iron stain
90
serum ferritin level that is virtually diagnostic of absent body iron store
< 15 ug/L
91
consists of 20-40% of developing erythroblast with visible cytoplasmic ferritin granules representing iron in excess of that needed for hemoglobin synthesis
sideroblasts
92
Iron accumulates in dysfunctional mitochondria
ringed sideroblast - appear as a necklace ring around the nucleus
93
ringed sideroblast is commonly seen in what condition
myelodysplastic syndromes
94
Intermediate in the pathway of heme synthesis which accumulates within red cells when heme synthesis is impaired
protoporphyrin
95
most common causes of increased levels of red cell protoporphyrin (2)
1. absolute or relative iron deficiency
| 2. lead poisoning
96
Causes of hypochromic, microcytic anemias (4)
1. IDA
2. thalassemias
3 anemia of inflammation
4. myelodysplastic syndromes (least common)
97
Goals of therapy in IDA (2)
1. anemia correction
2. provide stores of 0.5 to 1 g of iron
treatment for period of 6-12 months after correction of anemia
98
Amount of iron needed by an individual patient is calculated by the following formula:
BW (kg) x 2.3 x (15-Hgb (g/dL)) + 500 or 1000 mg
99
Most distinguishing feature between true IDA and iron-restricted erythropoiesis associated with inflammation
serum ferritin
inflammation: 3-fold increase in serum ferritin
100
acute infection can cause a fall in the Hgb levels of ____ within ____
2 to 3 g/dL
1-2 days
101
Mechanism of anemia of acute infection
faster destruction of nearly senescent RBCs (hemolysis of RBCs near end of their life span)
102
T or F. CKD sec to hypertensive kidney disease have more severe EPO deficiency for a given level of renal failure
false. DM
103
Hormones that augment erythropoiesis
testosterone and anabolic steroids
castration and estrogen administration in males will decrease erythropoiesis
104
If with decrease in Hgb while on EPO, consider the following pathology (4)
1. infection
2. iron depletion
3. aluminum toxicity
4. hyperparathyroidism
105
a monoclonal proliferation of mature B lymphocytes defined by an absolute number of malignant cells in the blood (5 × 10^9/mL)
Chronic lymphocytic leukemia (CLL)
106
Median age of diagnosis of CLL
71
primarily a disease of older adults
107
T or F. CLL is linked to to radiation exposure
False. CLL is one of the only types of leukemia not linked to radiation exposure
108
T or F. CLL is one of the most familial-associated malignancies.
True. first-degree relative of a CLL patient has an 8.5-fold elevated risk of developing CLL than the general population
109
Distinction of CLL from normal B cells
BCR signaling
110
BCR signaling of CLL that is different from normal B cells
1. low-level IgM expression
2. variable response to antigen stimulation
3. tonic activation of antiapoptotic signaling pathways that promote tumor survival
111
One of the most influential prognostic factors identified in this disease is the mutational status of the immunoglobulin heavy chain variable (IGHV) region
CLL
112
Because IGHV sequencing was initially cumbersome to perform, a number of surrogate factors have been identified; however, none yet have been shown to be equal or superior to IGVH sequencing. The most prevalent of surrogate markers for CLL are (3)
Zap-70 expression
ZAP-70 methylation
surface CD38 expression
113
Besides IGHV mutational status, _______ are the most robust prognostic factor clinically available in CLL
recurrent cytogenetic abnormalities
The most well-characterized abnormalities include del(13) (q14.3), trisomy 12, del(11)(q22.3), and del(17)(p13.1)
114
Cytogenetic abnormalities in CLL that is associated with more indolent disease, prolonged survival, and good response to traditional therapies
del(13)(q14.3)
115
Cytogenetic abnormalities in CLL that results in deletion of the ATM gene and is associated with bulky lymphadenopathy and aggressive disease in young patients, with inferior prognosis, more rapid progression to symptomatic disease, and shorter survival
del(11) (q23.3)
116
Cytogenetic abnormalities in CLL that results in loss of one allele of the tumor suppressor TP53 and is associated with the poorest prognosis in CLL with rapid disease progression, poor response to traditional therapies, and shorter survival
del(17)(p13.1)
117
Mutation in what gene in CLL that is commonly associated with trisomy 12
NOTCH1
118
Mutations have been associated with lower sensitivity of CLL to CD20 antibody therapy and increased risk of transformation to aggressive diffuse large B-cell lymphoma (DLBCL; Richter’s transformation).
NOTCH1
119
The most common cytogenetic abnormality in CLL
del(13)(q14.3)
120
When there is elevated total white blood cell (WBC) count with lymphocytic predominance or a normal WBC with a differential showing a lymphocytosis and a blood disorder is suspected, what is the next step?
Flow cytometry
121
In cases in which the clonal B cell count based on flow cytometry is ≥5 × 10^9/L, the diagnosis is
CLL
no further workup is needed to confirm the diagnosis of CLL
122
A semantic designation from CLL that denotes a primarily tissue-based disease rather than bone marrow/blood-based disease
small lymphocytic lymphoma (SLL)
small clonal proliferation of CLL cells in the peripheral blood but will also have lymphadenopathy or splenomegaly
123
Patients who do not meet the diagnostic criteria for CLL based on quantification of clonal B cells in the peripheral blood and who do not have associated signs of CLL including lymphadenopathy, organomegaly, or cytopenias have a disorder known as
monoclonal B-cell lymphocytosis (MBL)
which is now thought to precede every case of CLL but not all MBL progresses to CLL
124
leading cause of both disease-related morbidity and death in patients with CLL
Infections
125
The most common types of cancers seen in CLL are (3)
skin cancers, prostate, and breast cancers
All CLL patients should be counseled on the use of sunscreen while outdoors and should undergo preventative skin examinations
126
Most common autoimmune complications in CLL
Autoimmune cytopenias most commonly AIHA
Second most common is immune thrombocytopenia
127
Sydroe of combination of AIHA and ITP
Evan’s syndrome
128
In CLL, treatment for ITP is usually instituted when (3)
1. platelet levels drop to 20–30,000
2. Evidence of bleeding complications
3. need for invasive procedures
129
One of the most devastating complications of CLL wherein there is transformation of CLL to an aggressive lymphoma
Richter’s transformation
130
CLL most commonly transform into what lymphoma
DLBCL
131
Risk factors for Richter’s transformation (4)
1. bulky lymphadenopathy
2. NOTCH1 mutations
3. del(17)(p13.1)
4. specific stereotyped IGVH usage
132
1st diagnostic test in suspected cases of Richter’s transformation
18FDG-PET/CT (fluorodeoxyglucose–positron emission tomography combined with computed tomography) scan
Standardized uptake values (SUV) <5 is consistent with CLL and can rule out Richter’s trans- formation in many cases. SUV >5 are suspicious for Richter’s transformation, with SUV ≥10 very concerning
133
two widely used staging systems in CLL
Rai staging system
Binet system
Both characterize CLL on the basis of disease bulk and marrow failure
134
T or F. Imaging and bone marrow analysis is a requirement in staging CLL
False. Staging only rely on physical examination and laboratory studies
135
standard therapies for CLL
Chemotherapy and chemoimmunotherapy
136
For CLL patients who are young (≤65 years), the gold standard for therapy is
Fludarabine + cyclophosphamide + rituximab (FCR)
nucleoside analogue fludarabine, the alkylator cyclophosphamide, and the anti-CD20 monoclonal antibody rituximab (FCR)
137
For older CLL patients or those with multiple comorbidities, standard for therapy is
Chlorambucil + obinutizimab OR bendamustine + rituximab
138
first agent to show a survival advantage in CLL
Rituximab
139
a reversible, p110 delta isoform-specific PI3K inhibitor used in treatment of CLL
Idelalisib
B-Cell Receptor Signaling Inhibitors
140
a relatively selective, irreversible inhibitor of Bruton’s tyrosine kinase (BTK) in CLL
Ibrutinib
This target is attractive because, unlike other kinases in the BCR pathway, BTK does not have natural redundancy and is selective for B cells, so inhibition leads to a B-cell–specific phenotype
141
Antiapoptotic therapies for CLL target
BCL2
142
Following the completion of therapy or during therapy for indefinite targeted agents in CLL, response is initially assessed using
PE and laboratory studies
If residual disease is not detected using these methodologies, CT scans are used to assess response
Bone marrow biopsies with flow cytometry are indicated if no disease is detected to confirm CR
143
In CLL, if no malignant cells can be detected in the bone marrow down to a level of______, the patient is said to be negative for minimal residual disease (MRD)
1 CLL cell in 10^4 leukocytes (0.01%)
144
CLL Rai stage if lymphocytosis only
Low risk (stage 0)
145
CLL Rai stage if lymphocytosis with lymphadenopathy, with or without splenomegaly or hepatomegaly
Intermediate risk (stage I/II)
146
CLL Rai stage if lymphocytosis with anemia or thrombocytopenia due to bone marrow involvement
High risk (stage III/IV)
147
CLL Binet stage A is ____ areas of lymphadenopathy
<3
148
CLL Binet stage B is ____ areas of lymphadenopathy
≥3
149
CLL Binet stage C is Hgb of ____ and Platelt of ____
≤ 10 g/dL
< 100,000/uL
150
Symptoms Indicating Need for Therapy in CLL (5)
1. Evidence of progressive marrow failure (worsening of anemia or thrombocytopenia not due to autoimmune destruction)
2. Massive (≥6 cm below costal margin), progressive, or symptomatic splenomegaly
3. Massive (≥10 cm), progressive, or symptomatic lymphadenopathy
4. Autoimmune anemia or thrombocytopenia not responsive to standard therapy
5. Constitutional symptoms (one or more of the following: unintentional weight loss ≥10% over 6 months, significant fatigue, fevers ≥100.5°C for 2+ weeks without infection, night sweats for >1 month without infection)
151
Complete response in CLL therapy in terms of
```
Lymphocyte count
Lymph nodes
Spleen/Liver size
Bone marrow
PBS counts
```
Lymphocyte count: <4000/μL
Lymph nodes: None >1.5 cm
Spleen/Liver size: Not palpable
Bone marrow: Normocellular, <30% lymphocytes, no B lymphoid nodules
PBS counts: Platelet count >100,000/μL, Hemoglobin >11 g/dL, Neutrophils >1500/μL
152
CML is the consequence of the balanced translocation between chromosomes
9 and 22 (t[9;22][q34;11])
153
CNL has been associated with a translocation of chromosomes
t(15;19) translocation
154
CEL occurs with a deletion or balanced translocations involving what gene
PDGFRa gene
155
Myeloproliferative disorders that are characterized by driver mutations that directly or indirectly constitutively activate JAK2, a tyrosine kinase essential for the function of the erythropoietin and thrombopoietin receptors and also utilized by the granulocyte colony-stimulating factor receptor
```
polycythemia vera (PV)
primary myelofibrosis (PMF)
essential thrombocytosis (ET)
```
156
A clonal hematopoietic stem cell disorder in which phenotypically normal red cells, granulocytes, and platelets accumulate in the absence of a recognizable physiologic stimulus
Polycythemia vera
157
The most common of the myeloproliferative neoplasms
Polycythemia vera
158
A mutation in the autoinhibitory pseudokinase domain of the tyrosine kinase JAK2 that replaces valine with phenylalanine (V617F), causing constitutive kinase activation—appears to have a central role in the pathogenesis of
Polycythemia vera
159
A member of an evolutionarily well-conserved, nonreceptor tyrosine kinase family and serves as the cognate tyrosine kinase for the erythropoietin and thrombopoietin receptors.
JAK2
160
most common cytogenetic abnormality in PV
heterozygosity on chromosome 9p involving the segment containing the JAK2 locus over time due to mitotic recombination (uniparental disomy)
161
Homozygosity for JAK2 V617F is expressed most frequently in
PV (60%)
| lesser extent in PMF (50%) but is rare in ET
162
Cytogenetic abnormality that is the basis for many of the phenotypic and biochemical characteristics of PV such as increased blood cell production and increased inflammatory cytokine production
JAK2 V617F
However, it cannot solely account for the entire PV phenotype and is probably not the initiating lesion in any of the MPN
163
Symptom that distinguish PV from other causes of erythrocytosis
aquagenic pruritus
164
Hepatic venous thrombosis is also known as
Budd-Chiari syndrome
PV should be suspected in any patient who develops hepatic vein thrombosis
165
Erythema, burning, and pain in the extremities, a symptom complex known as________, is a complication of thrombocytosis in PV due to increased platelet stickiness.
erythromelalgia
166
Unless the hemoglobin level is _____(hematocrit_____), it is not possible to distinguish true erythrocytosis from disorders causing plasma volume contraction.
≥20 g/dL
≥60%
167
Relative erythrocytosis due to a reduction in plasma volume alone is known as
stress or spurious erythrocytosis or Gaisböck’s syndrome
168
Only three situations cause microcytic erythrocytosis:
β-thalassemia trait
Hypoxic erythrocytosis
PV
169
The assay for _______ has superseded other tests for establishing the diagnosis of PV.
JAK2 V617F
170
T or F. A bone marrow aspirate and biopsy of PV provide no specific diagnostic information because these may be normal or indistinguishable from ET or PMF
True
171
The most significant complication and often the presenting manifestation of PV
Thrombosis due to erythrocytosis
172
In PV, maintenance of the hemoglobin level at ______ and hematocrit _____ in men and hematocrit ____ in women is mandatory to avoid thrombotic complications.
≤140 g/L (14 g/dL)
<45%
≤120 g/L (12 g/dL)
<42%
173
In most PV patients, once an iron-deficient state is achieved, phlebotomy is usually only required _____ intervals.
at 3-month
174
T or F. Neither thrombocytosis nor leukocytosis are correlated with thrombosis in PV, in contrast to the strong correlation between erythrocytosis and thrombosis.
True
175
T or F. The use of salicylates is given to prevent thrombosis in PV patients.
False. It is not only potentially harmful if the red cell mass is not controlled by phlebotomy, but is also an unproven remedy.
176
Given in PV when chemotherapy is used to avoid further elevation of the uric acid
Allopurinol
177
Treatment of generalized pruritus in PV (4)
JAK1/2 inhibitor, ruxolitinib
pegylated interferon α (IFN-α)
psoralens with ultraviolet light in the A range (PUVA) therapy
hydroxyurea
Intractable to antihistamines or antidepressants such as doxepin and can be a major problem in PV
178
Managemnt of symptomatic splenomegaly in PV (2)
Ruxolitinib
| Pegylated IFN-α
179
A phosphodiesterase inhibitor that can reduce the platelet count and, if tolerated, is preferable to hydroxyurea because it lacks marrow toxicity and is also protective against venous thrombosis while hydroxyurea is not
Anagrelide
180
Alkylating agents and radioactive sodium phosphate are avoided in PV because they are
leukemogenic in PV
181
Preferred cytotoxic agent in PV
Hydroxyurea
But this drug does not prevent either thrombosis or myelofibrosis in PV, is itself leukemogenic, and should be used for as short a time as possible
182
JAK2 inhibitor used in PV
Ruxolitinib
183
Chronic PMF (other designations include idiopathic myelofibrosis, agnogenic myeloid metaplasia, or myelofibrosis with myeloid metaplasia) is a clonal hematopoietic stem cell disorder associated with mutations in (3)
JAK2
MPL
CALR
184
Chronic primary myelofibrosis is characterized by (3)
marrow fibrosis
extramedullary hematopoiesis
splenomegaly
185
Least common myeloproliferative neoplasm
Primary myelofibrosis
186
Myeloproliferative neoplasms that present with myelofibrosis (3)
Polycythemia vera
CML
Primary myelofibrosis
187
Primary myelofibrosis primarily afflicts
men in their sixth decade or later
188
T or F. BMA is the diagnostic test to detect myelofibrosis in PMF.
False. Marrow is usually inaspirable due to the myelofibrosis. But marrow biopsy will reveal a hypercellular marrow with trilineage hyperplasia and, in particular, increased numbers of megakaryocytes in clusters and with large, dysplastic nuclei
189
T or F. PMF is a diagnosis of exclusion
True.
190
Management of PMF
glucocorticoids + low-dose thalidomide
Roxulitinib
Allogeneic bone marrow transplantation
191
The most distressing and intractable problem for PMF patients
Splenomegaly
Causing abdominal pain, portal hypertension, easy satiety, and cachexia
Surgical removal of a massive spleen is associated with significant postoperative complications including mesenteric venous thrombosis, hemorrhage, rebound leukocytosis and thrombocytosis, and hepatic extramedullary hematopoiesis with no amelioration of either anemia or thrombocytopenia when present. For unexplained reasons, splenectomy also increases the risk of blastic transformation.
192
The only curative treatment for PMF and should be considered in younger patients and older patients with high risk disease
Allogeneic bone marrow transplantation
193
ET (other designations include essential thrombocythemia, idiopathic thrombocytosis, primary thrombocytosis, and hemorrhagic thrombocythemia) is a clonal hematopoietic stem cell disorder associated with mutations in (3)
JAK2 (V617F)
MPL
CALR
194
Essential thrombocytosis sex predilection
Female
195
Usual PE in essential thrombocytosis
Usually unremarkable except for mild splenomegaly
| Significant splenomegaly is indicative of another MPN, in particular PV, PMF, or CML.
196
In essential thrombocytosis, this electrolyte abnormality is common but is a test tube artifact only
Hyperkalemia
The large mass of circulating platelets may prevent the accurate measurement of serum potassium due to release of platelet potassium upon blood clotting
197
Absent marrow iron in the presence of marrow hypercellularity is a feature of
PV
198
Appears to be the most important risk factor for thrombosis in ET patients
tobacco use
199
Very high platelet counts are associated primarily with hemorrhage due to acquired
von Willebrand’s disease
