Flashcards in Heme Deck (367)
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1
Normoblasts
Nucleated RBCs
2
Reticulocytes
When nucleated RBCs lose their nucleus (5-7 days)
3
What causes left shift of O2 binding
Increase pH
Decrease DPG/Temp
4
What causes right shift of O2
Decreased pH
Increased DPG/TEMP
5
What is the major Hemoglobin structure for adults
HbA (alpha/beta) 95%
6
Why are RBCs binconcave in shape
Enables max O2 saturation
Allows passage through small capillaries and splenic sinusoids
7
Anemia
Lower than normal total circulating red cell mass
8
Mean cell volume
MCV
Volume of RBC
Femtoliters
9
Mean cell hemoglobin
MCH
Average content of Hb
Picograms
10
Mean cell hemoglobin concentration
MCHC
Concentration of Hb in given packed RBCs
11
Red cell distribution
RDW
Coefficient of variation of RBC volume
12
Anemia due to acute hemorrhage, what is the immediate concern
Hypovolemia
13
Are the majority of hemolytic anemias found intravascular or extravascular
Extravascular
14
Intravascular hemolysis Causes
Complement fixation: BIGGEST! think of blood mismatching
Mechanical injury
Infections/ intracell parasites, toxins
15
What happens to RBCs in extravascualr hemolysis
RBCs rendered less deformable
RBCs thought as foreign
16
Lab: PB- normochromic, normocytic anemia, increased reticulocytes
BM- erythroid hyperplasia
Serum: Increased unconjugated bili, increase LDH, low haptoglobin
Hemolytic anemia
17
Urine: hemosiderinuria, +/- hemoglobinuria
Intravascular hemolysis
18
Hereditary intrinsic RBC defects
Spherocytosis: membrane defect
G6PD: Enzyme defect
Sickle: hemoglobin defect
19
Acquired extrinsic RBC defects
Immune mediated damage
Nonimmune mediated damage
Sequestration- hypersplenism
20
Who has highest incidence of spherocytosis
N. Europeans
21
What is the genetic pattern for spherocytosis
AD
22
What is the lifespan of RBCs in spherocytosis
10-20 days
23
What are the proteins affected in spherocytosis
Ankyrin (75%)
Band (20%)
Ankyrin, spectrin, band 4.1, band 4.2
24
Why is there splenomegaly in spherocytosis
Deformed RBC (more spherical) unable to traverse splenic sinusoids, phago by splenic macrophages
25
Tx of spherocytosis
Splenectomy
26
mild to chronic hemolytic anemia
Induced aplastic/ hemolytic crisis
hereditary spherocytosis
27
What is the one test for spherocytosis
Osmotic fragility test
In 65% of patients RBCs lyse prematurely when exposed to hypotonic salt solutions
28
G6PD is in which cycle
Hexose monophosphate shunt (glutathione metabolism)
29
What are the G6PD variants which cause disease
A: 10% africans
Mediteranian: mostly middle east
30
G6PD is protective against
P. Falciparum malaria
31
What is the most common G6PD varient in people
G6PD B
32
Heinz bodies
Denatured hb in RBCs
G6PD
33
Oxidation where causes hb to denature/ precipitate
SH groups on globin chains hb
34
Bite cells
G6PD
Splenic macrophages bite out inclusions (extravascular)
35
Genetic of G6PD
Recessive X linked
36
Acute hemolysis after oxidant stress, infection, fava beans
G6PD
37
Hemoglobinopathies
RBC dz mutation in globin genes
Defective hemoglobins
38
Thalassemia syndromes
Lesions in globin genes
Decreased synthesis of globin chains
39
Genetic issue in sickle cell
Point mutation of position 6 in beta globin gene
Glutamic acid replaced by valine
40
40% HbS
Heterozygote sickle cell trait
AS
41
Sickle is protective against
Falciparum malaria
42
Malaria endemic where
Essentially all non "white" countries
43
Is sickling in Sickle cell reversible
Initially, but at chronic stage its not
44
Which hb's predispose to sickling
HbA/HbF - decrease sickle
HbC- Increased sickle
45
What predisposes you to increased sickling in sickle cell
HbC
Dehydration
Low pH
Low O2 tenison
46
What predisposed you to decreased sickling
HbA/HbF
co existing a-thalassemia
47
Pt presidposed to encapsulated bacteria
H influ
Pneumococcus
Hyperslenism kids
Autosplenectomy pts
Sickle pts
48
Why hypersplenism in kids during sickle cell
Repeated farction/fibrosis
49
Where does sickle crisis take palce (vaso-occlusive)
Microvascular occlusions
Kids- kidneys
Adults- leg ulcers
50
Sequestration cirsis
Kids/young adults
Rapid pooling of blood in spleen
Sickle cell
51
Aplastic crisis
Acute viral infection
Parvo B19 (infects red cell precursors)
Sickle cell
52
Diagnosis of sickle
PB- sickled cells
Mix blood with metabisulfite (should induce sickling)(reduction test)
Hb electrophoresis
DNA screen
53
What is one way to increase HbF to tx sickle cell
Hydroxyurea
54
Give prophilactic what for sickle cell
Penicillin
55
Outcome of HbSS
50% survive to age 50
56
What is the major cause of death in sickle for child <5
infection
57
What is most likely going to kill someone with sickle
Acute chest syndrome
Stroke
Adult- organ failure
58
Is thalasemia intrinsic or extrinsic hemolytic anemia
Intrinsic
59
Lab- Hypochromic, microcytic, low levels of normal Hb
Insoluble inclusions
Thalassemia
60
Beta globin gene is found where
Chrom 11
Point mutation of beta
B1/ B2
61
Alpha globin gene found where
Chrom 16
Deletion of alpha globin chain
a1/a2/a3/a4
62
Distribution of thalassemia
Old world distribution
63
B thalassemia
Diminished synthesis of struct normal B globin chain
unpaired a chain production
64
B+ thalassemia
Reduced B chains produced
Mutation in promotor region of gene
65
Bo Thalassemia
No B chains made (homozygote)
Mutation in splicing or chain termination
66
75% of precursor RBCs normoblasts die in hyperplastic bone marrow
Ineffective erythropoiesis
B- thalassemia
67
WHat is absorbed in excess with B thalassemia
Dietary iron
68
What is seen with severe b thalassemia
Extramedullary hematopoiesis
69
B thalassemia major
B+/B+, B+/ B0, B0/B0
70
What type of anemia is seen in B thalassemia major
Severe transfusion dependent anemia
71
B Thalassemia Minor/ Trait
B+/B or B0/B
72
What type of anemia is seen in B thalassemia minor/trait
Mild asymptomatic anemia
73
B thalassemia intermedia
Milder versions of 1 thalassemia
Severe variants in 2
1 combined with a thalassemia
74
Folks at high risks of B major
Meiterranean
Parts of Africa
SE asian
75
When does B thalassemia being to appear
6-9 months since HbF starts to fall
76
Hb levels in B thalassemia
Hb: 3-6 g/dl
HbF remains high
HbA2 normal, low or high
77
Pt presents with expansion of hematopoietic marrow- prominent facial bones, erosion of bony cortex, new bone formation
Hepatosplenomegaly
Hemosiderosis
B thalassemia major
78
Pt comes with mild hypochromic microcytic anemia
Electrophoresis shows increase HbA2, Incr or normal HbF
Typically asympotomatic
B thalassemia minor
Make sure not to tx with iron (iron overload will be exacerbated
79
How do you tx B thalassemia
Regular blood transfusions
Iron chelators to prevent overload
Bone marrow transplant
80
a thalassemia silent carrier
one a gene deleted
81
a thalassemia trait
2 a genes deleted
a/a -/- (SE Asian)
a/- a/- (African)
82
Which a thalassemia variety can produce offspring with severe a-thalassemia
SE asian variant
a/a -/-
83
Hemoglobin H disease (HbH)
a thalassemia... 3 genes deleted
84
Hydrops fetalis
a thalassemia... 4 genes deleted incompatible with life
85
Pathogenesis of HbH
excess B chains with a lack of a chains, has a high affinity for O2, produces severe tissue hypoxia.
HbH prone to oxidation-> inclusions in older RBCs-> extravascular hemolysis (spleen)- > moderate anemia
86
Pathogenesis of Hb Barts
Excess of gama chains in utero-> extremely high O2 affinity, O2 doesnt reach tissues
87
How do you tx Hb Barts
Intrauterine transfusions
88
Genetic paroxysmal nocturnal hemoglobinuria
Mutations of X linked gene of phosphatidyloinositol glycan class A (PIGA)
Rare acquired clonal stem cell disorder- associated with periodic hemolysis
89
Pathogenesis of paroxysmal nocturnal hemoglobinuria
Defective PIGA-> Needed to synthesize GPI- cell membrane glycolipid anchor for attachment of certain proteins to cell surfaces
Selective advantage hypothetically gained via autoimmune destruction of GPI linked proteins Hemolysis occurs
90
Absence CD markers are associated with Paroxysmal nocturnal hemoglobinuria
CD55, CD59, C8 binding protein
Increases susceptibility to hemolysis
91
Pt Presents with
Chronic low grade hemolysis (intravascular hemolysis)
Mild/ moderate anemia
Hemoglobinuria hemosiderinuria
Absence of CD55/ CD59
Paroxysmal nocturnal hemoglobinuria
92
What is the leading cause of death in paroxysmal nocturnal hemoglobinuria
Thrombosis (40% DVT)
93
What is the possible autoimmune link to paroxysmal nocturnal hemoglobinuria
Aplastic anemia
94
Possible cancers linked to Paroxysmal nocturnal hemoglobinuria
AML
Meylodysplastic syndrome
95
Tx of PNH
immunosuppression/ bone marrow transplantation
96
Complication of PNH
Iron deficiency
97
Tests used for diagnosis of immune hemolytic anemias
Cooombs test
Direct antiglobulin test (DAT)
Indirect Antiglobulin Test ( IDAT)
98
Direct antiglobulin Test
DAT
Detection of antibodies+/- complement on patient RBCs
INcubate w/ cold: IgM
Incubate w/ warm: IgA IgG
99
Indirect antiglobulin Test
IDAT
Test serum for ability to agglutinate test RBCs that have known antibodies bound to them
100
Which immunohyemoltic anemia is most common
Warm
101
Reason for warm immunohemolytic anemia
50% idiopathic
50% predisposing diseases( autoimmune disease, lymphoma, drug reactions)
102
Reason for cold immunohemolytic anemia- Acute self limited hemolysis
Infections
Mycoplasma pneumonia
Infectious mono
CMV
Influenza
HIV
103
Reason for cold immunohemolitic anemia- chronic hemolysis
Idiopathic
Associated with low grade lymphoma
104
What are the causes of hemolysis due to mechanical RBC damage
Cardiac valve prosthesis
Microvascular obstruction
DIC
Malignant HTN
SLE
Cancer
105
Defect of what in aplastic anemia
Stem cell defect
106
Cause of megaloblastic anemia
Defective Vitamin B12 or Folate
107
Why is B12 and folate needed
DNA synthesis
108
MCV>100
Megaloblastic anemia
109
Pt Macrocytic anemia
Decreased in reticulocyte count
Hypersegmented neutrophils
Hypercellular hematopoiesis
Megaloblastic anemia
110
What requires B12
Methylmalonyl coA -> succinyl coA
111
Increased Methyl malonic acid in Urine
B12 deficiency megalblastic anemia
112
Pt presents with doral and lateral tract degeneration
Subacute combined degeneration affecting sensory and motor functions
Lower limb parasthesias
Megaloblastic anemia
Vit B 12
113
What in diet contains B12
Animal products
114
How is B12 absorbed
Pepsin and pancreatic proteases release B12 from food-> B12 binds to IF from parietal cells-> active absorption in ileium
115
Where does B12 get absorbed
Ileum
116
Causes of B12 def
Decreased intake (strict veg)
Impaired absorption (prenicious anemia)
Increased requirement (prego/growing child)
117
Mech of prenicious anemia
Immune destruction of gastric mucosa
Failure of IF production
B12 not absorbed
118
Prenicious anemia seen in
N. Europeans 40-80 yrs
119
Pt presents with Megaloblastic anemia
Low B12
Inc serum homocysteine and methylmalonic acid
Can determine b12 def or prenicious anemia
120
What is very specific test for prenicious anemia
serum antibodies to IF
121
Do reticulocytes respond to B12 when deficient
Yes
122
Where is folate absorbed
Jejunum
123
Where do we get folate from
Green vegs/ fruits.... SHould be raw... cooking destroys folate
124
Causes for folate deficiency
Decreased intake (inadequat diet/ alcholics)
Impaired absorption
Increased requirements (prego/ infancy)
125
PT megaloblastic anemia
Inc Homocysteine
Dec in folate
No neuro issues
Megalobalstic Folate def
126
What is the most common anemia
Iron def
127
Causes of iron def
Dietary def (dev countries)
Imapaired absorption
Increased requirements
Chronic blood loss
128
Location of chronic blood loss for iron def
GI bleeds
Menstraul bleeds
129
Where is iron obtained from
Animal products
130
Where is iron absorbed
Duodenum
131
What inhibits the storage of iron, once theres iron in excess
hepcidin
made in the liver
132
Ferritin
Storage of iron
133
Hemosiderin
Partly degraded aggregates of ferrritin
134
Transferrin
Iron transport
135
Normal serum iron levels
100-120 micrograms
136
CBC low HB/MCV; high RDW
Blood smear: hypchromic poikilocytosis- pencil cells
Low iron/transferrin, ferritin
Iron deficiency anemia
137
Stain BM with prussian blue and no stain... what does that mean
No iron stored in BM
138
What is the most common anemia in hospitalized patients
Anemia of chronic disease
139
Three main groups for the cause of chronic dz
Chronic bacteria/ immune/ malignant tumors
140
iron anemia with decreased erythropoiesis
Anemia of chronic disorders
141
Lab-
Normo- hypochrom microcytic
Inc: ferritin
Dec: serum iron, TIBC, Erythropoitetin
Anemia of chronic dz
142
Iron def vs anemia chronic dz
ACD: Transferrin reduced or low, Ferritin normal/inc
IDA: Transferrin increased, ferritin reduced
143
Pancytopenia
BM failure
Aplastic anemia
144
How is aplastic anemia transferred to people
Congenital/ hereditary (fanconi anemia)
Acquired
145
Idiopathic Aplastic anemia etiology
65% of cases
Possibly immune related destruction of stem cells (t cells)- Suspected in most cases
Possibly intrinsic stem cell defect
146
Acquired aplastic anemia etiology
35% of cases
Chemical agents: (chemo/ idiosyncratic )
Physical agents: whole body radiation
Viral agents: Hepatitis (not ABCG), CMV/ EBV/Herpes zoster
147
Lab-(PB)
Pancytopenia
Normo chromic/cytic
Low reticulocyte count
BM
Hypocell, only fat cells, scattered stroma
Aplastic anemia
148
What is necessary to dx aplastic anemia
Bone marrow biopsy
149
Who is expected to fully recover from aplastic anemia
Children since it is probably viral etiology
150
Tx aplastic anemia
Allogeneic bone marrow transplant in younger patients
Immuno suppression in older adults
151
What can cause BM failure
Aplastic anemia
Myelophthisic anemia
Diffuse liver disease
Chronic renal failure
152
Myelophthisic anemia
BM replaced by abnormal infiltrates (replaced w/ fibrosis)
Metastatic ca, granulomatous inflammation
PB- leukoerythroblastic
153
Diffuse liver dz BM
BM hypofunction, affects mainly RBCs
154
Chronic renal failure BM
Multifactorial anemia
Drop in erythropoietin (produced in kidney)
155
Polycythemia
Abnormally elevated RBC concentration
156
Relative polycythemia
Due to reduced plasma volume
Secondary to dehydration
157
absolute polycythemia is broken into what
Primary/ secondary
158
Primary absolute polycythemia
Polycythemia vera
Chronic myeloproliferative neoplasm
159
Secondary absolute polycythemia
Appropriate EPO levels: lung dz, cyanotic heart dz, living in mountains
Innappropriate EPO- EPO secreting tumors (kidney/liver cancers)
160
Prolonged bleeding time indicates
Platelet defect
161
Prothrombin time (PT) tests
Extrinsic and common coagulation pathways
162
Partial thromboplastin time (PTT)
Test of intrinsic and common pathways
163
Thrombin time tests
Fibrinogen
164
Thrombocytopenia
Reduced number of platelets, prolonged bleeding times
165
Functionally abnormal platelets
Normal platelet count, prolonged bleeding times
166
Etiology of acquired platelet function abnormalites
Drugs- Nsaids
Uremia- chronic renal failure
167
Causes of thrombocytopenia
Decreased platelet production
Decreased platelet survival
Sequestration in spleen
Dilutional
168
Etiology of decreased production of platelet
BM dz
Aplastic anemia
Marrow infiltration
Drug induced
Infections
Megaloblastic anemia
Myelodysplastic syndromes
169
Etiology of decreased platelet survival
Immune destruction
Non immune destruction
170
Immune destruction of platelets
Antiplatelet antibodies
Autoimmune: Primary ITP (immune thrombocytopenia), Secondary ITP (SLE/lymphoma)
Isoimmune: Post transfusion (seen in neonates)
Drug associated: Heparin/ antiB
Infection associated: HIB/CMV/ Mono
171
Non immune destruction of platelets
DIC
TTP/HUS
Giant hemangiomas
Microangiopathic hemolytic anemias
172
Acute primary immune thrombocytopenia
Uncommon
Children
Post viral
Spontaneous resolution
173
Chronic primary immune thrombocytopenia
Common
Women 20-40
Skin/mucosal bleeding
Does not resolve spontaneously
174
Tx of ITP
immunosupression (steroids)
Splenectomy
175
Lab-
Dec: Platelets (ones present are large)
Inc: Bleeding time, megakaryocytes in BM biopsy
Antib against platelet membrane glycoproteins
Chronic immune thrombocytopenia
176
Non immune thrombotic thrombocytopenic purpura
Syndrome of fever
Thrombocytopenia
Microangiopathic hemolytic anemia
Transient neuro deficits
Renal failure
177
Non immune thrombotic hemolytic uremic syndrome
No neruologic defecits (vs TTP)
178
Common features of TTP/ HUS
Formation of platelet thrombi in small bv
Platelet consumption- thrombocytopenia
Platelet thrombi- small vessel occlusion
nonimmune thrombotic
179
Hereditary clotting disorders
Factor VIII
Von Willi
Factor IX
180
Acquired clotting disorders
Typically multiple factor abnormalities
Vit K def
Liver dz
DIC
181
What are the most common inherited bleeding disorders
Factor VIII Hemophil A
Von Willibrand factor
182
Factor VIII function
Cofactor for Factor IX to activate Factor X
Intrinsic pathway
183
VWF function
Promotes adhesion of platelet to the subendothelial layer after damage
Prolongs the half life of Factor VIII
184
What are the AD transmission types of von willebrand dz
Type 1/3: reduce quantity of VWF
Type 2 qualitative functional abnormality of VWF
185
Type 1 VW dz
70% of all cases of vwd
mild mucosal bleeding
186
Type 2 Vw dz
25% of all cases of vwd
Mild to moderate bleeding
187
Type 3 VW dz
Severe deficiency/lack of VWF
affects F VIII stability
188
Who would present like hemophilia A
Type 3 VW dz
189
Transmission of Hemophilia A
X linked recessive
190
CLinical-
Massive bleeding after trauma/surgery
Lab- Normal platelets, BT, PT
Prolonged PTT
Hemophilia A/ Factor VIII deficiency
191
Tx of hemophilia A
Recombinant FVIII infusions
192
Pathophys mech of DIC
Systemic activation of coagulation sequence
Formation of microthrombi
Consumption of platelets/ clotting factors, secondary activation of fibrinolysis
193
Disorders associated with DIC
Obstetric
Infections
Neoplasms
Massive tissue injury
194
Leucopenia
Too few cells
195
Leukocytosis
Too many cells
196
Lymphopenia seen in
Advanced HIV
Chemo/steroids
Autoimmune dz
Acute viral infections
197
Pathogenesis of neutropenia
Reduced production by BM
Accelerated consumption/destruction (peripheral problem)
198
Reduced production of neutrophils etiology
Suppression of myeloid stem cells (aplastic anemia)
Suppression of committed myeloid precursors (drug related)
Ineffective granulopoieisis(mega anemia)
Marrow infiltration
Kostmann syndrome
199
Etiology neutrophil peripheral loss
Immune related (idiopathic dz, drugs)
Splenic sequestration (splenomegaly)
Increased consumption (infection)
200
Agranulocytosis
Severe neutropenia
Prone to infections
<500
201
Etiology of severe neutropenia
Drug induced
Chemo
202
Neutropenia pathology
BM morphology
Infections secondary to agranulocytosis (candida/ aspergillus)
203
Clinic
Infection
Post chemo (granulocyte colony stimulating factor
Neutropenia
204
Etiology of Neutrophilic leukocytosis
Infections
Acute inflammation
Acute hemorrhage
Malignancy
205
Etiology Eosinophilic Leukocytosis
Allergic disorders
SKin dz
Parasites
Drugs
Collagen vascular dz
Drug rx
206
Etiology basophilic leukocytosis
Indicates myeloproliferative neoplasm
207
Etiology monocytosis
Chronic infections
Collagen vascular dz (SLE)
Inflammatory bowel dz
208
Etiology lymphocytosis
Chronic immunological stimulation
Mono
VIral infections (EBV/HEP A/ CMV)
B. Pertussis
209
Dohle bodies
Sky blue cytoplasm found on neutrophils
210
Activated large lymphocytes with flowing cytoplasm seen in
Viral infections
211
CLninc- Large swollen grey/red lymph node, localized site of infection
Acute lymphadenitis
212
Chronic lymphadenitis signs
Follicular hyperplasia-b cell response
Paracortical hyperplasia- T cell response
Sinus histiocytosis- dilated sinusoids, containing phagocytic histiocytes
Medulla- plasmacytosis
213
General pathogenesis of WBC neoplasias
Chromosomal translocations/oncogenes
Inherited genetic factors
Viruses
Environ agents
Iatrogenic
214
What inherited genetic factors increase risk for WBC neoplasias
Downs
215
What viruses increase risk for WBC neoplasias
EBV, HTLV1, KSHV/HHV-8
216
Leukemia
Neoplasia with predominant BM involvement /PB as well
217
Lymphoma
Neoplasia w. masses in lymph nodes/extranodal at time of presentation
218
Acute WBC neoplasias
Has Precursor cells predominates
219
Chronic WBC neoplasias
Differentiated mature cells predominate
220
Clinical-
Non tender lymph node enlargement
NHL
HD
221
40% of NHL is what
Extranodal
Will have site related sx
222
BM replacement -> cytopenias is a sign of what
Leukemias
223
Bone pain due to path fx sign of what
Plasma cell neoplasms
224
What do you use in lab to investigate lymphoma
Histological examination
PCR/Southern blot to detect antigen receptor gene rearrangment
225
What lab investigation used for B cell neoplasms, and what would you see
Flow cytometry or immunohistochemical stains
Detect light chains Kappa/ lambda chains!
226
Most common NHL
B cell lymphomas 90%
T cell 10%
227
Most common B cell lymphoma
Diffuse large B cell lymphomas
Follicular
Small
MALT
MCL
228
Clinical-
Painless lymphadenopathy
Found to be late stage with BM involvement
Liver/Spleen involvement
Follicular lymphoma
229
Age for follicular lymphoma
40-60
230
Where does follicular lymphoma arise from
Germinal center B cells
231
What is characteristic of aggressive Follicular lymphomas
Diffuse pattern
Increased number of large cells
232
CDs for follicular lymphomas
CD19/20/10+
233
Translocation found in follicular lymphomas
14;18
234
Outcome of follicular lymphoma
Indolent/ incurable
40% transform to aggressive DLBL survival <1 year
235
Age for diffuse large b-cell lymphoma
Median 60
Wide age range
236
Clinical-
Single enlarged mass (60%)
Extranodal mass (40%)
B sx
Stage I/II
Negative BM
Diffuse large B cell Lymphoma
237
What can be primary or 2ndary to transformation from previous low grade lymphoma
Usually Follicular lymphoma will transform to this
Diffuse large B cell lymphoma
238
Diffuse large B cell lymphoma outcome
Aggressive
Potentially curable
CXT (chemotherapy)
239
What is the most common adult leukemia
Chronic lymphocytic leukemia
240
What is the common age for CLL
>50 yrs
241
CLinical-
Early- incidental finding of lyphocytosis in CBC
Later- Progressive BM replacement
Autoimmune hemolytic anemia
Thrombocytopenia
Large LNs, liver, spleen
Small lymphocytic lymphoma/ Chronic lymphocytic leukemia (SLL/CLL)
242
Lab-
PB: Smudge cells (due to fragility)
BM: Interstitial nodules-> diffuse replacement
LN: Diffuse pattern lymphocytes, some small some large
SLL/CLL
243
What are the CDs for SLL/CLL
CD19, 20, 5, 23, 43
244
Outcome of SLL/CLL
Incurable
Overall survival 4-6 years
245
COD for SLL/CLL
Progressive pancytopenia -> Infections/ bleeding
Transformation into more aggressive neoplasm -> Prolymphocytic leukemia (20%), Diffuse large B cell (10%)
246
Clinical-
Small mature looking lymphocytes extranodal at mucosal sites
Mucosal sites acquired lymphoid tissue from chronic infections or autoimmune dz
Marginal zone lymphoma (maltoma)
247
What is the most common site of Marginal zone lymphoma
Stomach- usually superimposed on helicobacter gastritis
248
One way to tx Marginal zone lymphoma
Antibiotics to remove the helicobacter gastritis that is usually found with MALT
249
Marginal zone lymphomas can be found in salivary thyroid glands in conjunction with what
autoimmune inflammation
250
Burkitt lymphoma is associated with what virus
EBV
251
Burkitt with 100% EBV association
African (endemic)
252
Burkitt with 15% EBV association
Sporadic (non-endemic)
253
Burkitt with 25% EBV association
HIV associated Burkitt
254
Lab-
Diffuse medium sized cells high mitotic rate w. apoptosis
Starry sky pattern
Burkitt
255
What CD is associated with Burkitt
CD 19/20/10
256
What translocations are associated with Burkitt
(8;14), (2;8), (8;22)
257
Burkitt cell is associated with translocation of chrome 8... what does this code for
Chrome 8= c-myc oncogene
258
Endemic/ sporadic Burkitt seen in what age
kids/ young adults
259
Where are the extranodal masses located for burkitts
Endemic: mandible, kidneys, ovaries, adrenal glands
Sporadic: Abdominal
260
Which age group has a worse prognosis for burkitts
Older adults
261
What is best tx for burkitts
CTX high dose
262
Age for hairy cell leukemia
middle aged males
4:1 M:F
263
Clinical/ Lab-
Pancytopenia/Splenomegaly
PB- Cells with kidney shaped nuclei/ pale, blue cytoplasm
Bleb extensions
BM- Small lymphocytes abudent ctyoplasm (fried egg appearance)
Dry tap
Spleen: Red pulp infiltration
Hairy cell leukemia
264
CDs associated with Hairy
CD 20, 11c, 25, 103+
265
Multiple myeloma has an increase in what
IgG
266
Waldenstrom macroglobulinemia has an increase in what
IgM
267
Heavy Chain dz has an increase in what
H Chains
268
Primary amyloidosis has an increase in what
light chains
269
Age and sex for multiple myeloma
Mid age or older (50-60)
M>F
270
Clinical-
Bone pain (vertebrae, ribs, skull)
Cytophenias-> marrow replacement
Organomegaly
Bacterial infections
Renal insufficiency
Multiple myeloma
271
Why is there renal insufficiency in multiple myeloma
hypercalcemia
Bence jones proteins
Amyloid deposition
272
M protein in serum/urine
Lytic bone lesions
multiple myeloma
273
What is the sign to dictate therapy for multiple myeloma
end organ damage
274
Tx for multiple myeloma
Alkylating agent ctx
Younger pts can have allogeneinc bone marrow transplant
275
Differences between HD and NHL
HD: tumor cell minority, Orderly spread, very little extranodal involvement, Involvement of single axial node group
NHL: Tumor cells majority, Spread is not predictable, Extranodal presentation normal, multiple peripheral nodes involved
276
Lab-
Altered germinal center b lymphocytes (reed sternberg)
Non neoplastic inflammatory cells
HD
277
Clinical -
Painless rubbery enlargement of lymphnodes
Pain is found only after drinking
B sx: fever, night sweats, weight loss,
itching
HD
278
Ann arbor staging for HD
I single node region
II 2 or more LN on same side of diaphragm
III LN on both sides diaphragm
IV multiple/disseminated involvement of 1 or more extralymphatic organs/ tissues
279
CD in classical HD
CD 15+, 30+, 45-
280
CDs in varient HD
CD 20+, 45+, 15- 30-
281
Path classification classical HD
Nodular sclerosis 65%
Mixed cellularity 25%
Lymphocyte rich
Lymphocyte depleted
282
Path classification of variant HD
Lymphocyte predominant 5%
283
Clinical-
Adolescents/ young adults M=F
Mediastinal involvement
Stage I/II
Classical HD
284
Lab-
Large nodules surrounded by thick fibrous collagen bands
Reed-sternberg cells/ lacunar cells
Classical HD
285
Age of mixed cell HD
Young adults, then again >55 M>F
286
Mixed cell HD
Diffuse nodal replacement
RS cells
EBV+
287
Lymphocyte depleted HD
Abundant RS cells
EBV +
few lymphocytes/ fibrosis
288
Who at risk for lymphocyte depleted HD
Elderly, HIV+, usually present at advanced stage IV
289
Large nodules
RS cells/ popcorn cells
EBV negative
Varient HD (lymphocyte depleted)
290
CLinical features or lyphocyte depleted HD
Certival ax nodes
Can recur
<5% transform to NHL large B cells lymphoma
291
Age of lymphocyte depleted HD
35, M>F
292
Prognosis of HD
Long term survivors get secondary cancers (AML, lung ca)
293
Majority of acute lymphoblastic leukemia/ lymphoma presents as
b-cell types
Childhood acute leukemias
294
15% of ALL presents as
precursor T cell neoplasms
Medistinal mass
Usually seen in adolescent males
295
ALL vs AML
Morphology: AML- granules/ auer rods
Histo stain: ALL- MPO, Sudan black. AML- PAS
ALL abnormal cytogenetics
296
Clinical-
abrupt severe sx
Bone pain
Enlargement of LNs, liver, spleen
Thymic enlargement
Testicular enlargement
CNS involvement
ALL
297
What is seen in T cell- ALL
Thymic enlargement
298
What is seen in B cell- ALL
Testicular enlargment, CNS involvement (headaches, blurred vision, vomiting)
299
Good prognosis for ALL
2-10 yrs
WBC count low
Immunophyenotype: pre b cell
Cytogentics: hyperdiploidy t(12;21)
300
What is the translocation for ALL that gives a good prognosis
t (12;21)
301
Adverse prognosis for ALL
100,000
t(9;22)
302
Which translocation gives a bad prognosis for ALL
9;22
303
Primary involvement of myeloid neoplasms
BM, peripheral blood, secondary hematopoietic organs (liver, spleen, nodes)
304
Age for AML
adults, peaks after 60
305
Clinic-
Acute onset
Bone pain
enlarged organs (liver/spleen/LN/ brain)
Monocytic differentiation on tissue
AML
306
WHO classification of AML
1. AML w/ recurrent chrom rearrangements
2. AML w/ multilineage dysplasia
3. AML, therapy related
4. AML, not specified
307
What is linked to M3 classification of AML (acute promyelocytic leukemia)
recurrent chromosomal rearrangements
308
M0-M3 lineages of AML are based on
maturation of granulocyte
309
M4-M7 lineages of AML based on
Blast cells
310
Translocations seen in AML
15;17, 8;21, 16;16
Seen in younger adults with AML
311
Which translocation is not a good prognosis for those with AML
Translocations involving chromosome 11
312
Deletion/ monosomy of chrome 5/7 seen in
Older adults with AML
or post chemo
313
AML pathogenesis
Translocations disrupts differentiation
Chimeric genes-> block terminal differentiation
Mutated tyrosine kinase-> increased cell proliferation
Accumulation of proliferating neoplastic precusors in BM- suppresses normal hematopoitic progenitors
314
AML infiltration of skin is associated with which monocytic differentian
M4/M5
315
DIC is associated with AML in what translocation
15;17
316
Best diagnostic method of diagnosing AML
1.BM aspirate/ biopsy
FLow cytometry
Cytogenetics
317
Tx of AML with (15;17)
Chimeric protein- RARa-PML blocks differentiation beyond promyelocytes
Tx with vitamin A deriverative (all trans retinoic acid)
318
What translocation for AML has a better prognosis
8;21
inv 16
319
What translocation for AML intermediate prognossi
15;17
320
What has a poor prognosis for AML
Del 5 or 7
321
Myelodysplastic syndromes (MDS)
Clonal maturation defects in stem cells causing abnormal differentiation
322
Idopathic/ primary myelodysplastic syndrome (MDS) age
>50, gradual onset
323
Therapy related MDS age
2-8 yrs
324
MDS complication
transforms to AML
Survival 9-30 months
325
Lab-
PB: Macrocytic anemia, +/- blast cells
BM: hypercellular, disorganized hematopoiesis, abnormalities of RBC, granulocytes, megakaryocytes
MDS
Severe MDS increased blast cells
326
Abnormal chromosomes 5/7, trisomy 8
MDS
327
Tx of MDS
allo-BMT in young
supportive rx in older pt
328
Pathogenesis of Chronic myeloproliferative neoplasms
Arise from multipotent progenitor cells
Mutated- constitutively activated TK- circumvent normal growth controls
329
Mutation in CML
t(9;22) Phila
BCR-ABL fusion
Result- constitutively ABL kinase activation
330
Mutation in polycythemia vera
JAK2 point mutation
Result- constitutive JAK2 kinase activation
331
Essential thrombocythemi/ primary melofibrosis mutation
JAK2 point mutation
MPL point mutation
Constitutive kinase activation
332
Chronic MPN myeloproliferative neoplasms
BM filled with neoplastic cells. supress normal hematopoiesis
Transforms to CML
333
Age sex of CML
25-60 M>F
334
CLinical-
Gradual onset weakness, loss of appetite
Abdominal discomfort from enlarged spleen
CML
335
CML
Defect in pluripotent stem cell for myeloid and lymphoid lineages
Mainly granulocytic, uncontrolled proliferation
336
Lab-
PB: Left shift leukocytosis (neutophils, myelocytes, eosinophils, basophils)
BM: INC granulocytes, megakaryocytes
CML
337
What translocation seen in CMl
9;22
Philadelphia, BCR-ABL
338
CML tx
Imatinib- inhibits BCR-ABL kinase
Allogenic bone marrow transplant good for younger pts
339
Spherocytosis is associated with which anemia
autoimmune haemolytic anaemia
340
Spheroctosis leads to what
Elevated unconjugated bilirubin
GALL STONES
– SPLENOMEGALY
– Howell Jolly bodies (purple blue nuclear remnants) may be present after splenectomy i.e. removal of spleen
341
Heinz bodies also seen in what
HbH
342
Haemoglobinuria (red or dark coloured urine)
• Jaundice and rapid reticulocytosis
• Splenomegaly and gall stones
G6PD
343
What is destroyed in PAROXYSMAL NORCTURANAL HAEMOGLOBINURIA
CD 55 (decay accelerating factor)
– CD59(membraneinhibitorofreactivelysis-potentinhibitorofC3 convertase
344
What is the effect of destroyed CD markers in PNH
Susceptible to complement especially in acidic states (sleep)
345
Test for PNH
Ham test
346
Test for autoimmune hemolytic anemia
Autoimmune haemolytic anaemias are Coomb’s
test positive
• Direct Coomb’s test
– anti – Ig antibody (antihuman antiglobulin) is
added to patient’s RBCs
– Agglutinate if RBCs are coated with anti-RBC
surface Ig
• Indirect Coomb’s test
– Normal RBCs and anti-Ig antibody are added to
patients serum
347
Target cells
Sickle cell
348
What gives the "crew cut" appearance
Sickle
B-Thalasemia major
349
Howell Jolly inclusions seen in
Single dot of nuclear remnant
Postsplenectomy
– Haemolyticanaemia
– Megalobasticanaemia
350
Basophillic stippling found in
Leadpoisoning
– Thalassaemia(esp. βthalassaemia major)
– Megaloblasticanaemia
351
Why is there iron overload in b thalassaemia major
Ineffective erythropoiesis
352
FEP and Zn protophyrin levels are elevated in what
since synthesis of Hb requires Iron to be inserted into protoporphyrin IX
Iron Def anemia
353
Lab-
deposits of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell.
Sideroblastic anemia
354
Etiology of aplastic anemia
Idiopathic
– Inherited (Fanconi’s anaemia)
– Acquired – drugs (most common cause of all), viruses (e.g. Hepatitis C) chemicals, toxins,
irradiation
355
INFECTIOUS MONONUCLEOSIS is associated with what viruses
EBV
CMV
Toxoplasm
356
Pathogenesis of Mono
Proliferation of B cells
Antibodies against IgG IgM
357
Atypical lymphocytes or Downey cells in peripheral blood
• Irregular nuclei, basophilic vacuolated cytoplasm, peripheral condensation of cytoplasm
Ballerina cells MONO
358
LAB-
Stains positive for PAS (acid phosphatase stain) and for TDT (terminal deoxynuclotidyl transferase enzyme stain
ALL
359
Stain positive for tartate resistant acid phosphatase (TRAP)
Hairy cell leukemia
360
Clinical massive splenomegaly
Hairy cell leukemia
361
Production of osteoclast-activating factor (OAF) a.k.a. IL6
Lytic lesions
Multiple Myeloma
362
Rouleaux formation in multiple myeloma from
hyperviscostiy syndrome
363
Severe low back pain indication of
Multiple myeloma
364
megakaryocytesReleaseofgrowthfactors(TGFβandPDGF) by megakaryocytesextensive fibrosis and angiogenesis
megakaryocytes- > Release of growthfactors (TGFβ and PDGF) by megakaryocytes -> extensive fibrosis and angiogenesis
365
Which factor is from the extrinsic pathway
7
366
Which factors form intrinsic pathway
12, 11, 9, 8
367