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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

megakaryocytesReleaseofgrowthfactors(TGFβandPDGF) by megakaryocytesextensive 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

Which factors form common pathway

5, 2, 1