Hematology: Anemia

Definition: RBC count, Hb, Hematocrin O2 carrying capacity Tissue hypoxia

Symptoms
Signs
Fatigue/ weakness
Pallor in conjunctiva, tongue, mucus
SOB
membrane
Headache
O2 carrying capacity
Exercise Tolerance
Tachycardia & bounding pulse
The above sym due to O2 supply
(hyperdynamic circulation)
Palpation
Heart pumps fast & strong
Heart pumps fast & Stroke Vol. Cardiomegaly Congestive heart
discomfort
failure
Cardiac failure
Heart muscle hypertrophy
CO & Stroke Vol.
Displace of apex beat
Angina
Cardiomegaly
Heart muscle hypertrophy, blood Retinal hemorrhage from fundus
supply ischemic heart
exam.
Visual disturbances
CO?, hypoxia of retina?
Retinal hemorrhages in very
severe anemia
Classification of Anemia
Base on cause
Base on RBC indices
Failure of RBC production (production
Size of RBC (MCV)
problem)
Haemoglobinization (MCH)
Loss/ destruction of RBC
(destruction)
Bone Marrow: site of blood cells production
BM has 6 times reserve: BM erythropoiesis when peripheral destruction
4 types of production problem:
1. Empty factory: aplastic Anemia
Myelodysplastic
2. Deficiency of raw materials: Fe, B12,
4. Infiltrative: Myeloma, Lymphoma,
Folate
Cancer, TB
3. Ineffective production of BC:
5. Erythropoiesis: process of RBC
production occurring in BM
6. Critical factors:
BM environment: stromal cells
give the appropriate structure
(fibroblast, etc.)
Stem cells: normal proliferation
& maturation
Vital material: B12, Fe, folate
Growth factors: erythropoietin
produced by kidneys, used as
drug
7. Shape of RBC: Biconcave, central
pallor
1. surface area to vol. ratio
2. Not burst easily & withstand pressure
8. Immature RBC:
9. Nucleus/cytoplasm ratio, presence of fine chromatintranscription rate,
Cytoplasm maturation: Blue pink
10. Abnormal RBC

11. Polychromatophilia
RBC color with various shades of blue tinged with pink/
purple & bigger
Reflects immature RBC
Suggests reticulocytes in blood & MCV
Varying RBC hemoglobin content
12. Microcytosis
< than the smallest WBC, MCV
< 80 fL
Always with hypochromia
13. Hypochromia
Abnormal Hb
Central pallor > than half of
diameter
Low level of MCHC
14. Macrocytosis
Larger than normal WBC, > 95 fL
15. Possible DDx of abnormal RBC
16. Microcytosis
17. Macrocytosis (*=common)
Fe deficiency anemia
Pernicious anemia* (MCV > 120 fL)
Thalassemia
Megaloblastic anemia: B12/folate
Anemia of chronic disease
deficiency
Hemoglobinopathies
Myelodysplastic syndromes
Disorders of porphyrin & heme
/hematological malignancies
synthesis & vit. B6 responsive
(ineffective to produce blood cells)
sideroblastic anemia
Chronic liver disease /alcoholism
Hypothyroidism
18. Hypochromic
Myeloma
Fe deficiency anemia
Hemolytic anemia* /reticulocytosis
Thalassemia
In cold agglutinin disease* MCV > 125
Hemoglobinopathies
RBC clumping falsely high
Chronic disease
Physiological: Neonatal, pregnancy
sideroblastic
Chemotherapy (which targets DNA
synthesis, hence RBC)
19. Hypochromic
20. Normochromic
21. Macrocytic
microcytic Anemia
Normocytic Anemia
Anemia
Fe deficiency
After acute blood loss
Megaloblastic
Thalassaemia
Mixed cases (Fe MCV +
(must about BM):
Anemia of chronic
Folate MCV Normal
vit. B12, folate
disease (RA causes
MCV)
deficiency
mal function of Fe
Anemia of chronic disease
Non-megaloblastic:
rather than Fe
Hemolytic Anemia
alcoholism, liver
deficiency, congenital
(sometimes reticulocytes
disease,
heart failure)
may lead to MCV) (Burn,
hypothyroidism,
Lead poisoning
DIC, TTP: microangiopathetic
myelodysplasia etc.
(abnormal RNA)
hemolysis, fragment RBC)
22. Anemia due to production problem

23.
Bo

ne marrow failure syndrome

Pancytopenia: in RBC, WBC and PLT and reticulocytopenia (young RBCs)
Primary hematological conditions: Aplastic Anemia, acute leukemia
Secondary to BM infiltration: Malignant (carcinoma) or granulomatous infiltration
Anemia is only part of the cytopenias and diagnosed and managed in the context of
BM failure
Anemia is only part of the cytopenias and diagnosed & managed in the context of
BM failure

24.
25.
26.
27.
28.
29.
30. Fe deficiency Anemia
31. Diagnosis
1. Complete blood count / red cell indices:
Hb, MCV, MCH
Reticulocyte count (may after Fe therapy)
Platelet count may, WBC usually within limits (BM production but not suff. Fe
to produce RBC)
2. Peripheral smear:
target cells, pencil cells, HcMc blood picture
3. Serum iron study:
Fe , TIBC , % Saturation , Ferritin
4. Red Cell inclusion (Test for alpha thalassemia):
For exclusion of alpha thalassemia
5. S/S for severe cases:
Koilonychia: the nails are concave ridged and brittle

6.
7.
8.

Angular cheilosis: fissuring and ulceration at the corners of the mouth

Postcricoid web (Plummer-Vinson Syndrome)
Ix the cause of iron deficiency:
GI
9. Renal Tract
Ulcer, tumor, varices,
10. Haematuria, hemoglobinuria (PNH)
haemorrhoids, aspirin,
hookworm, inflammatory blowel 12. Uterine
diseases, bleeding,
13. Menorrhagia, ante- & postpartum,
malabsorption: atrophic
multiparity.
gastritis, partial gastrectomy
15. Poor diet
16. Poor quality diet, especially if mostly
vegetable
17. Sideroblastic anemia
18. Sub-type of MDS, named refractory anemia with ring sideroblasts
19. Congenital
20. Acquired
Hereditary sex-linked occurring in
Primary
males
21. classified as one of the
Autosomal
myelodysplastic syndromes
Very rare, produce hypochromic
Associated with malignant marrow
microcytic anemia
disorders
22. Acute leukaemias, myelodysplastic
syndromes, polycythaemia vera,
myelomatosis, etc.
Secondary
23. Drug e.g. isoniazid, cycloserine
24. Toxin e.g. alcohol, lead
25. Megaloblastic Anemia
26. Miscellaneous e.g. pregnancy,
rheumatoid arthritis, haemolytic
Anemias
27.
28.
29.
Siderotic granules
(Pappenheimer bodies)
are iron granules in RBC
Hypochromic microcytic
red cells
Ringed sideroblasts
30. Megaloblastic anemia
Group of anemia which
erythroblasts in BM
shows characteristic
abnormality, maturation
of the nucleus being
delayed (defective DNA
synthesis) relative to that of the cytoplasm
Nuclear cytoplasmic maturation asynchrony: The nucleus of RBCs has delay
maturation but the cytoplasm has normal maturation.
31. Diagnosis
32. Complete blood count / red cell indices
Hb, MCV , MCH normal
Reticulocyte count
WBC, neutrophil count, platelet BM problem
33. Peripheral smear

 Oval macrocytes, Howell-Jolly bodies (nuclear fragments)

Basophilic stippling
Hypersegmented neutrophils (>5% neutrophils with >5 lobes, normal 3-4 lobes)
34. Bone Marrow
Hypercellularity (ineffective)
Megaloblastic erythropoiesis (nuclear
maturation defects), after 48 hrs of B12
injection back to normal
Giant myelocytes and band cells (-ditto-)
Cannot recover in short time by B12
injection
35. Biochemistry
bilirubin LDH ( turnovers of red cell and
their precursors)
36. Cause
Vitamin B12 deficiency
Folate deficiency
Abnormalities of B12 or folate
metabolism, transcobalamin deficiency,
nitrous oxide, anti-folate drugs, these 2 drugs rapidly inhibit B12 function
Other defects of DNA synthesis:
Congenital enzyme deficiencies: Orotic aciduria
Acquired: Alcohol, therapy with hydroxyurea, cytosine arabinoside
37. Function of B12:
Neurologic myelination
RBC production
38. Pernicious anemia
A significant cause of B12
deficiency, which contributes to
megaloblastic anaemia
Epidemiology: late middle age,
northern European
Aetiology: an autoimmune
mechanism
39. B12 vs. Folate deficiency
40. Tests
41. B12 deficiency
42. Folate deficiency
43. Serum B12
44. Low
45. N /borderline
46. Serum folate
47. N /raised
48. Low
49. RBC folate
50. N /Low
51. Low
Serum folate is not accurate as when pts w/ folate deficiency but take high folate
supp before testing, it gives normal test result
B12 deficiency can cause neurological deficit and folate replacement (large doses)
should only be given for macrocytic anaemia when B12 deficiency has been ruled
out.
52.

53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.

Hemoly
sis: a
reduction of the red cell life span to below the normal value of 120 days (usually
down to hours to days)
76. When there is a mild problem, we dont consider as a problem. Even life span is 60
days, the pts still normal as compensation.
77. Hemolytic anemia: anemia resulted from rate of RBC destruction
78. But premature death of RBC doesnt consider as hemolysis
79. Lab features of HA
CBC
Hb, RBC (* in thalassaemia), Hct

MCV Reticulocytes (young RBCs) = polychromasia

WBC & platelets (reactive increase of hematopoiesis) in BM

Blood film
Polychromasia ( number of bigger and bluish RBCs)
Microspherocytosis (smaller and spherical not biconcave RBCs), lost central
pallor as no longer biconcave and becomes spherical shape
Biochemistry of RBC destruction

serum unconjugated (indirect) bilirubin, since the RBC is broken down outside
liver

urine urobilinogen; faecal stercobilinogen

serum haptoglobin which binds to Hb, as metabolism
Bone marrow features of compensatory RBC production
Bone marrow showing erythroid hyperplasia
80. Extra-vascular haemolysis
81. Intra-vascular haemolysis: (structural
protein defects, easy destruction)
82. Red cell destruction in reticulo84. Haemoglobinaemia: free Hb in blood
endothelial system, mainly in spleen,
85. Haemoglobinuria (Dark color
serum bilirubin (Jaundice)
urine)
83. DDx:
86. Haemosiderinuria
Warm (IgG) autoimmune haemolytic
87. DDx:
anaemias (AIHA), Warm type: IgG,
ABO mismatched transfusion IgM,
Cold type: IgM
very rapid circulation

Hereditary spherocytosis
G6PD deficiency
some allo-immune transfusion
some cold (IgM/complements) AIHA
reactions (mainly IgG, major immune
paroxysmal nocturnal haemoglobinuria
blood type mismatch)
88. Spherocytes:
w/o membrane, no central pallor, spherical & smaller
Myeloid: Erythroid ratio: N = 1/3
89.
90.
91.
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105. Classification of
haemolytic anaemia
106.
Hereditary: Intrinsic RBC
107.
Acquired: Extra-corpuscular or
defects
environmental change
1. Membrane: Spherocytosis
109.
Immune:
112.
(common in northern China);
110.
Auto/Allo- immune antibody
DAT
Elliptocytosis
against antigen on RBCs
+
2. Metabolism: G6PD; Pyruvate
111.
Drug-induced
Kinase (common in Western
countries)
113.
Red cell fragmentation
114.
3. Hemoglobin: HbE (common in
syndrome:
DAT
Thailand), HbS (Sickle cell
1. Mechanical valves, DIC
anaemia, common in Africa);
(microangioplastic), TTP
Thalassaemia (Non-structural)
(thrombic), heavy marching
108.
All give DAT -ve
2. Infections: Malaria, DIC
3. Secondary: Liver or renal diseases
115.
Direct-antiglobulin
test (DAT)
116.
Coombs reagent is antiIgM Ag which binds to the
IgM on the RBC surface if
present.
117.
AHG reagent is added
to washed RBCs,
agglutination+ve result
118.
DAT +ve
119.
DAT ve
120.
Immune related hemolysis
121.
Non-immune related hemolysis
present:
Intrinsic red cell defects
AIHA
Mechanical damage
drug induced HA
Infection
hemolytic transfusion reactions
HDN

122.
Hereditary Spherocytosis
Common in Northern China
Problem in RBC cell membrane, spherical RBCs
have weaker tolerance in osmotic changes
123.
G6PD deficiency
124.
When pts face oxidant stress, RBC
membrane are oxidized & GSH is required for
reduction which converts to GSSG. Since pts
lacks of G6PD, GSH cannot be recycled in RBC.
RBC lysis due to oxidized membrane.
125.
126.
Lab features:
Hb, reticulocytosis
Male: 4.4% (HK)
Peripheral blood smear
normal when no haemolysis
bite cells, blister cells
polychromasia, Heinz bodies (oxidized
denatured Hb)
127.
Sickle cell anemia
Structurally Abnormal Hemoglobin: beta
chain mutation, Hb S = 2S2
Forms crystal when exposed to low O2 tension
Deoxygenated sickle Hb polymerizes into long
fibers block circulation & cause infarction
128.
129.
130.
131.
132.
133.
134.
135.
136.
137.
138.
Acquired Immune Haemolytic Anaemia
(AIHA) (DAT +ve)
139.
Alloimmune
140.
Autoimmune
Haemolytic transfusion
141.
Warm (IgG)
142.
Cold (IgM)
reaction
Mediate destruction by cold agglutinin syndrome
Haemolytic disease of
binding of Fc portion of paroxysmal cold
the new born
cell-bound Ig by
haemoglobinuria (as
marcophages in spleen
intravascular lysis)
& liver (hence
splenomegaly)
Drug induced,
penicillin/ methyldopa,
Participate in
autoantibody
production
143.
Diagnostic tip for HA:
144.
DAT +
145.
DAT 146.
work up for immune
Abnormal RBCs (spherocytes, elliptocytes) + FHx
related hemolysis
RBC membrane defect
Bite cells, hemighost + DHx G6PD


147.
149.

AIHA Warm Ab type

151.
Cold agglutinin syndrome
152.
Note:
153.
The spherocytes
154.
The polychromatic cells
(Retics)
155.
The nucleated RBCs
156.
The red cell aggregations
157.
The small lymphocytes in
CLL
158.

Schistocytes, helmet cells + thrombocytopenia

Microangiopathic Prosthetic valve, DIC etc
148.
AIHA Warm Ab type with CLL
150.

159.

160.
Thalassemia Syndromes (Hb structurally normal)
161.
A heterogeneous group of diseases caused by the imbalance of globin chains (
to non- ), and manifested by a wide spectrum of clinical syndromes. The more
imbalance of alpha & beta, the more severe is the disease.
162.
Hb
163.
Structure
164.
% in normal adult 165.
% in birth
Hb
166.
A
168.
96-98
169.
167.
22
170.
A2
172.
1.5-3.2
173.
Trace amount
171.
22
174.
F
176.
0.5-0.8
177.
50-90
175.
22
178.
Gamma beta change at 3-6 months after birth
179.
Pathophysiology of Thalassaemias
180.
Minor (carrier)
181.
Intermedia
182.
major
183.
Hb (g/dl) = >10 184.
7-10
185.
= <7
Minor (carrier), intermedia and major depending on the degree of imbalance in the
production of globin polypeptide chains: more imbalance more severe
In thalassaemia
chain synthesis decreases, chain excessive
In thalassaemia
chain synthesis reduced; and in excess
186.
forming unstable tetramers: HbH ( 4), Hb Bart's ( 4)
187.
Hemolytic state/ Ineffective erythropoiesis/ Hypersplenism (enlarge spleen, most
cells stay in there) anemia
188.
Consequences:
defective globin chain synthesis

 globin chain imbalances

precipitate and damage red cell membrane
premature erythroid cell destruction in BM and blood circulation
189.
Genetics of thalassaemia: carrier in HK: 3.4%
190.
o thalassaemia, mutation at
191.
+ thalassaemia
chromosome 11
small deletions causing frame-shift
Pt mutation: A->G at nucleotide 28
mutations and premature termination
causing decreased transcription
(stop codon)
reduced mRNA
mRNA non-functional or absent
reduced chain synthesis = 5-30% of
no globin chain synthesis
normal (just reduction)
more common in Far East
No particular gene therapy
192.
Heterozygous thalassaemia: trait
carrier /0 ; /+
trait carrier
Asymptomatic with minimal anaemia
HbA2 (3.8-6.8%)
Mild reticulocytosis
HbA2 between 3.2-3.7%:
repeat test
exclude Fe deficiency
family study
HbF usually normal; some elevated low
MCV (55-70 fL); MCH (18-20 pg)
193.
Homozygous -thalassaemia ( 0/ 0 ;
0/ +; +/ +)
Major/intermedia
MCV, MCH
severe anaemia tissue hypoxia &
retardation of growth and development
Presence of HbF aggravates the hypoxia
(higher oxygen affinity than HbA)
Require frequent blood transfusion
Normal at birth
Anaemia becomes evident only after 3-6
months of age
Skeletal deformities, pathological fracture
Progressive hepatosplenomegaly
Retarded growth and sexual development
Intercurrent infection
Fe overload

194.
o
e
s

Anaemia
195.
Complication
Fe overload due to absorption by regular
massive transfusion each unit of blood
contains 200 mg Fe, normal body store ~1
g with no active excretion
tissue damage occurs at about 28 g (age
11-12) when ~100 units given
Three main organ systems affected:
cardiac, hepatic, endocrine
Chronic haemolytic state
Extra-medullary haemopoiesis result in
splenomegaly and hypersplenism
Increased turnover of bone marrow cells
causing
pigmented gall stones
hyperuricaemia
folate deficiency
196.
Genetics of deletional -thalassaemia: HK carrier: 5%
197.
0 -thalassaemia: transcription 198.
+ -thalassaemia: transcription
-ve chromosome 6
+ve
both genes are inactivated
only one of the pair is affected
(--SEA) deletion all the 4 copies gone
(-3.7) deletion , 0.3%
4.5%
(-4.1) deletion chrom 16, 0.2%
Deletion of complete - globin
gene cluster, 0.06%
199.
Prevalence of (--SEA) Deletion in
SE Asia
Thailand: 3-14%
Southern China: 5-8.8%
Northern Taiwan: 3.5%
200.
0 or + traits:
Asymptomatic with minimal anaemia but
low or close to normal MCV & MCH
201.
Hb Barts Hydrops Foetalis
Deletion of all four globin genes (0 /0)
Stillbirth as a result of a severe
erythroblastic anaemia, high output heart
failure and hydrops foetalis
Hb in cord blood 4-8 g/dL

C
ol
y'

 Peripheral blood: gross thalassaemia changes with

numerous normoblasts
202.
Hb H disease (0 /+) Laboratory
investigations
Inactivation of 3 globin genes
Hb 8.9 -12.7 (mean 10.4) g/dL (Thal trait or
intermedia)
MCV 71 fL (average)
MCH 18.5 pg (average)
Reticulocytes 5%
Bilirubin slightly increased
Self-life: 6-23 days
Ineffective erythropoiesis
Variable splenomegaly
203.
Hb H disease Dx
Demonstration of numerous red cells appearing like
golf balls with numerous HbH inclusions after
incubation with brilliant cresyl blue for 30
minutes at 37 oC
204.
Electrophoresis
HbH is unstable (needs a fresh sample)
HbH migrates to a position anodal to HbA (starch gel or
cellulose acetate electrophoresis at pH 8.6 and 7)
Small amount of Hb Barts (in 10% of patients)
205.
trait carrier: (+ /+, +/ 3.7/4.1 deletion, 0 / SEA
deletion)
206.
Management of thalassaemias
Accurate diagnosis: Conventional methods and genetic
investigations
Assessment of Fe status/overload & organ damage
Transfusion program: keep Hb >10g/dl at
all times
Fe chelation with Vitamin C
Folic acid
Splenectomy
Endocrine therapy, thyroid hormone to
prevent hypothyroidemia
Gene therapy: Allogeneic Stem cell (cord
blood) transplantation
207.

208. Bleeding Disorder

209.
Thro
mbotic
211.
Platel
et
212.
Clottin
g factors

210.
Anticoagulant
213.
Protein C
214.
Protein S
215.
Antithrombin III
216.
Fibrinolytic
system
217.
Imbalance between two system causes bleeding disorder or thrombosis,
Bleeding disorder is resulted from either thrombotic factors or anti-coagulant
218.
3 components of hemostatic mechanism:
219.
vascular
220.
platelet
221.
coagulation
component
222.
Vasoconstriction
223.
Platelet adhesion & 224.
Fibrin formation
aggregation
225.
General Approach to investigation of a bleeding tendency:
1. Investigation of a clinically suspected bleeding tendency: bleeding history, family
history, drug history.
2. Follow up an abnormal first line test.
3. Investigation of acute haemostatic failure: DIC
226.
Detailed Hx & P/E provide hints on most likely Dx, severity & guide Ix
227.
228.
Platelet & Vascular Disorder
229.
Coagulopathy
230.
Bleeding into skin (petechiae,
Bleeding at deep site
Site
ecchymosis)
At joint +/- slightly movement
Mucus membranes (epistaxis,
Haemarthrosis
menorrhagia, gum bleeding and
Haematoma
sometimes haematuria, melena)
231.
232.
Immediate (Severe bleeding
Delayed bleeding
Type of
during the time course)
Slow down & severe again (as
ble
vasoconstriction, platelet
edi
adhesion are function)
ng
233.
234.
Detailed DHx: aspirin/ aspirin236.
DHx: warfarin recurrent adj
Hx
like
of medication
235.
Recent change of medication is
237.
Fx: bleeding occurs at
important, eg antibiotic stopped
childhood, hereditary disease
recently
238.
239.
Platelet count
241.
Clotting tests
Ix
240.
Bleeding time
242.
Ascertain the bleeding Hx, Fx & DHx which may give clues of the presenting
disease:
243.
B Bleeding: physiological vs pathological
leedi Physiological: normal bleeding after cut
ng
Clinical suspect bleeding tendency: deep bleeding hemophilia in
Hx
young male
244.
F Von Willbrand: Autosomal dominant genetic disease
x
Hemophilia: X chromosome, affected maternal side male, test factor 8/
9 for hemophilia A/ B
245.
D SC bleeding: IV drug user
Hx
Ab?
246.
247.
Coagulation cascade:

The coagulation cascade consists

of:
Contact Activation pathway
(formerly known as the
Intrinsic Pathway) &
Tissue Factor pathway
(formerly known as the
Extrinsic pathway) - primary
pathway for the initiation of
blood coagulation
Leading to fibrin formation
Factor 5 is co-factor
TT: time for fibrinogen changes to
fibrin
Fibrin multimer is much harder
Fibrin monomer is the end time of
clotting test
APTT & PT are both are in vitro test,
in pts body not like this
New test: platelet function test which is more specific on platelet adhesion/
aggregation test
Factor II is prothrombin
Clotting tests: APTT, PT, TT, Fibrinogen level
Thrombin Time (TT): Prolonged w/ fibrinogen & heparin effects, common pathway
Problem in common pathway, both TT & APTT
Protein C: regulate/ balance/ natural inhibit blood clotting
248.
Basic Laboratory Tests:
All coagulate test plasma
Citrate traps K & preventing clotting
Prothrombin Time (PT) in vitro diagnostic test
Activated partial thromboplastin time (APTT)
Thrombin Time (TT)
Platelet count clumping: count as 1 cell/ even no count it
249. Why the blood would clump:
Slow blood drawing, Ab (anti EDTA, should using citrate instead)
Anesthesia concerns blood clumping problem
Bleeding time (BT) (rarely performed) in devo platelet function
250.
251.
252.
253.
254.
255.
256.
257.
258.
259.
Prothrombin Time (PT)
260.
DDx of Prolonged PT
Indicates the overall efficiency of
Administration of oral anticoagulant
extrinsic clotting system.
drugs (e.g. warfarin, for considering the
Depend on reactions with factor II, V,
effect of warfarin, we wont consider
VII, X and fibrinogen concentration of
APTT even it prolong)
the plasma.
Liver disease functional vitamin K
In patients on warfarin, the results are
deficiency
reported as an international
Vitamin K deficiency.
normalized ratio.
Factor II, V, VII and X deficiencies.

 Each manufacturer gives an ISI

(International Sensitivity Index) for any
tissue factor they make. The ISI value
indicates how the particular batch of
tissue factor compares to an
internationally standardized sample.
Why need ISI: Different lab doing test
on same subject would give same
result & compare results between labs
262.
Activated partial
thromboplastin time (APTT)
Indicates the overall efficiency of
intrinsic pathway.
Depends on contact factors, factor VIII
and IX, as well as factor X and V,
prothrombin and fibrinogen.
Sensitive to the presence of circulating
anticoagulants and heparin.

Differentially sensitivity: PT >> APTT

261.

263.
DDx of a prolonged APTT
(mainly APTT )
Factor VIII, IX, XI, XII deficiency
Administration of heparin (some time
using 2x of PT)
Lupus anticoagulant
264.
In case with a long APTT, a 50:50
mixture of normal and test plasma
should be tested to distinguish
between factor deficiency and the
effect of an inhibitor.
265.
Differentiate deficiency & inhibitor
Inhibitor: even factor no effect
Deficiency: after mixing normal APTT
266.
PT w/ Normal APTT
267.
APTT w/ normal PT
268.
Isolated PT deficiency of factor 269.
Isolated APTT deficiency of
7
factors in intrinsic pathway +
prekallikrein
270.
Hx can predict which factors have
problem, usually X link male member
(8, 9 factor)
271.
Hemophilia A/ B
Factor 8: Hemophilia A, Factor 9: Hemophilia B
X chromosome, female carrier & male subj would affected
Factor 11 is autosomal disease
Factor 12 has no role in bleeding as it involved in lab test deficiency of 12 has no
bleeding tendency
272.
273.
274.
275.
276.
277.
Both PT & APTT :
278.
Causes of Multiple clotting
Either multiple factor deficiencies
factors deficiencies/ DDx of
/single factor deficiency in common
prolong PT & APTT
pathway, eg 10, 5, thrombin,
Vitamin K deficiency, factor 5 & 10
fibrinogen
Oral anticoagulants: Warfarin, vit. K
Multiple factor deficiencies are more
and warfarin give normal TT time
common (7, 9)
DIC (Disseminated Intravascular
Acquire (recent onset) MFD are
Coagulation), consumption of factors,
vitamin K related 2, 7, 9, 10
TT, d-dimers +
Either one pathway problem is
Multiple factors deficiency, eg: Liver
uncommon
disease: early stage (PT affected
TT, short half life factor affect)
Factor II, V, VII, or X deficiency.
279.
Thrombin time (TT):
281.
DDx of Prolonged TT

Thrombin is added to plasma and the

clotting time measured.
The TT is affected by function
(quantity and quality, cannot bind) of
fibrinogen and the presence of
inhibitory substances (FDP,
heparin)
A patients TT should be within 2
second of the control. Times of 20s
and over are definitely abnormal
280.

Very prolonged TT presence of

heparin, corrected by protamine sulfate
indicates heparin contamination
(repeated test & corrected protamine
sulfate)
Heparin: thrombin time by binding
to anti-thrombin 3
Hypofibrinogenaemia congenital or in
DIC
Dysfibrinogenaemia inherited or in
liver disease
Raised concentration of Fibrin
Degradation Product as in DIC
Both APTT & PT , TT normal Vitamin
K, warfarin
282.
Heparin block: yellow bean on
dorsal hand for blood drawing, heparin
contamination
Presence of inhibitor, anti-thrombin
Heparin (anti-thrombin agonist)
Fibrinogen degradation production
DIC

283.
1:1 mixing with normal plasma:
Mix patients plasma with normal plasma in 1:1, PT & APTT is corrected factor
deficiency
If not corrected, inhibitors, Ab to clotting factors, factor 8 in hemophilia patients/
lupus anticoagulant
The normal sample is from normal result of other blood test
284.
Deficiency
285.
Inhibitors
286.
Tx: Transfusion
288.
Inhibitors are Ab, lupus
287.
Same picture to inhibitor but
anticoagulant, etc
management is diff.
289.
Ab against factors
290.
291.
292.
293.
Platelet count:
Normal platelet count: 150-450 x109, >50 is adequate for clotting
Before considering further investigation of a suspected bleeding disorder, always
check the platelet count and platelet morphology.
Confirm whether there is blood clumping which causes pseudothrombocytopenia
294.
Other laboratory tests:
D-dimer
Degraded product of fibrin, which has fibrin & cross link DIC
Diagnostic test for DVT
Fibrinogen
Von Willebrand factor, Ricof activity
Function of Von willebrand factor:
Stick factor 8 in order to half life
Platelet mediate function, permissive role
Differentiate the problem is platelet type/ coagulative type
Coagulation factors assay
Testing on factor 8, 9 2nd line test
Platelet function tests
Platelet count dysfunction, qualitative functional problem
Lupus anticoagulant

295.
Bleeding time test:
296.
Prolonged bleeding time:
Depth cut with BP cuff keeping BP at
Thrombocytopenia
40-50 mmHg
Defective platelet functions (eg von
Blood comes out and soaked the
Willebrands disease, thrombasthenia =
blood w/o touching the wound
platelet dysfunction)
Ask in EXAM
Vascular defect
297.
Hx suggests platelet/ vascular bleed
CBP if platelet <50 work up for thrombocytopenia
Platelet >50 (adequate) bleeding time test, if normal result, suggests the patient is
normal
bleeding time platelet defect/ vascular platelet function test
298.
Platelet Dysfunction
Aspirin
Uremia (renal failure), metabolite waste cause platelet dysfunction
von-Willebrands disease
299.
von-Willebrands disease
Always think of it
Autosomal platelet disorder
VWF factor assays, For EXAM purpose, do it when suspect
Ritocetin platelet aggregation, require VWF factor, normal have VWF factor for
aggregation
300.
301.
302.
303.
Low platelet count does not suggest bleeding tendency
Platelet is one of the factors
Pts has low platelet count due to DIC, TTP, HUS, heparin induced thrombocytopenia
may have thrombosis (as aggregation)
304.
Prolonged clotting time does not indicate bleeding tendency
APTT, PT are in vitro tests which cannot indicate the real situation in pts
Pts factor 10 deficiency has markedly APTT but no bleeding tendency
305.
Prolonged clotting tests (APTT, PT) associate w/ thrombosis
DIC, lupus anticoagulant associated with thrombosis (Not bleeding but thrombosis)
Prolong APTT bleeding & thrombosis
Not just relied on prolong APTT to predict thrombosis/ bleeding tendency
ONLY clinical Hx & clinical presentation decide whether patient has bleeding
tendency or not cause
When pt has APTT & thrombocytopenia: stroke thrombosis, severe bleeding
bleeding tendency
306.
Clinical question for assess pts whether have bleeding tendency:
Gum bleeding after teeth brush, stop by few wash/ long time for stop bleeding
Dental surgery, inspect if burise in arms, most serious: spontaneous bleeding
307.
Normal clotting test cannot exclude bleeding tendency due to coagulation
factors abnormality
308.
Because the test does not & cannot access, only assess vascular & platelet
parts
309.
Factor 13 deficiency, defects in plasminogen, plasminogen activatior
310.
Very rare
311.
Always ask what you can do for the patient with the lab test, either +ve/ -ve
result can help the Dx/ management when no, dont order the test
312.
Case study:
A 20 years old female history of easy bruising and heavy menstruation
APTT 34 sec (N 31-35 sec)
PT 12 sec
Plt 10 x 109/L

313.
314.
315.
316.
318.
319.
&
320.
321.

Dx & Ix
Blood film no clumping suggests thrombocytopenia
Find out the cause is production cause/ consumption cause
Production cause
317.
Consumption casue
Aplastic
322.
Ab/ immune
Lack of raw material, Treatable
Autoimmune
correctible
Infection
Ineffective
Drug
Infiltrate
b-cell lymphoma
neoplatic
323.
Non-immune
BM exam production suggests consumption problem
Bleeding time must , not order
Coombs test test anti-RBC Ab
ANF (Anti-nuclear Ab) for testing if lupus causes, if 3 parameters already known,
do it otherwise dont order Dx of lupus, fulfill 4/11 citeria
Anti-platelet Ab test
324.
Dx: Isolated thrombocytopenia
325.
Anti-platelet Ab, Coombs test, ANA, rheumatoid factors, complements are not
needed to do
Bone marrow examination was not an essential procedure in patient with isolated
thrombocytopenia and no other abnormalities clinically
Considered BM for patients over age 60, before splenectomy or other
expensive/toxic treatment modalities
Platelet antibodies are not specific for ITP
Antibodies to specific glycoproteins are more specific but not sensitive (50-65%)
Not useful for diagnosis in general
ANA, Rheumatoid factors & complements are needed unless indicated by other
clinical features
ITP is clinical Dx
326.
Tx:
Risk of bleeding related to the severity of thrombocytopenia.
Need to balance the risk (may be worse than the disease) and benefit of treatment
Achieve a safe platelet count but does not need to be normal
Treatment is not indicated for mild or moderate thrombocytopenia with no
haemostatic risk
327.
5 minimum in hematology
328.
Treatment, period, platelet count, side effect, Ix
329.
Causes of DIC:
Intrauterine death
Amniotic fluid embolism
Post-partum infarct
Sepsis/ septicemia
Prostate/ pancreas CA
330.

331. Transfusion Medicine, Thrombosis & Anticoagulant Therapy

332.
4R in Transfusion medicine
Right indications
Right products
Right way
Right patient
333.
Avoid reaction between patients Ab &
donar
red cell Ag
334.
Usually use patients serum to do
compatibility test
335.
Transfusion Reaction
336.
Ab & Ag reaction
337.
An 338.
Antig 339.
Status
tibodie
en status
s
of Donor
status
of
Recipi
ent
340.
+
341.
+
342.
Potential
serious
reaction
343.
+
344.
345.
No
reaction &
safe
346.
347.
+
348.
No
reaction &
safe
349.
Apart from ABO blood group, other minor blood group antigen test for minor
antigen (C, D)
350.
Patients bacterial flora produces B-like antigen naturally occurring antibodies
351.
352.
353.
354.
355.
356.
357.
358.
359.
360.
Why serum
grouping &
cell group
gives different result on same
patient?
Wrong patient
Immunodeficiency (common)
Lab error (least likely)
361.
Major blood group system
362.
ABO blood group & Rh
363.
Remaining 2%, find Ab or from a wider blood bank
364.
Direct crossmatch (past method)
Direct mixing of donor red cells with patients serum to determine whether there is
any antigen antibody reaction ( hemolysis, agglutination) in vitro, needed to test 4
units

 Incubation at 37oC for 1 hr

365.
366.
Drawback:
After transfusion, patient still bleeding need to retake sample
Long time (1 hr)
Order 8, 10 unit of blood sample for this test, big storage demand
367.
Antibody screen
Mixing of patients serum with pre-selected group O screening cells
Screening cells express all common red cell antigens, includes some minor blood
group antigen
368.
The screening cell from blood source from many blood banks
369.
Take voluntary blood cells, not only ABO but also many common minor antigens
370.
All ve: Ab free of minor blood group
371.
e.g blood group A + all ve result present of Ab B
372.
How long antibody screen remain valid?
Primary response (or called first exposure)
Secondary response (or called follow exposure)
72 hours time for follow exposure to develop Ab
373.
1st exposure: 10 14 days with 2 Ab
374.
Cover 90-99% Ab
375.
Discard the expire result as patient may expose to antigen at that period
376.
Antibody identification
377.
When patient does not have that antibody, it means he has that respective
antigen
378.
When to transfuse?
Hb (anemia + symptoms appear)
symptoms
379.
Efficiency + symptomatic efficiency
380.
Dont treat the number
381.
Transfusion rate is as fast as possible
Blood is stored in refrigerator w/ continue shaking
For shock patients, as fast as possible
Completed within 4 hrs in a bid to prevent bacterial growth
382.
Indication for platelet transfusion
383.
Active bleeding in a patient with thrombocytopenia
384.
Platelet transfusion
Active bleeding - < 50x109
Prophylactic < 10x109
Find out the causes of thrombocytopenia first
Not consumption problem but symptomatic Transfuse
Production problem Transfuse
Rate of platelet transfusion
Need of X-match
Need for ABO compatibility
Patient with blood group A: AB, A platelets are the 1st choice
Group O plasma contains both anti A, B
385.
FFP transfusion
Active bleeding and abnormal clotting profile( prolonged APTT, PT >1.5x normal)
FFP with significant amount of plasma which contains Ab
386.
Blood bank definition: 1 unit of FFP (10-15 ml/kg) = 1 pack of whole blood
387.
From 1 unit contains 1 unit of RBC, platelet & FFP respectively
388.
Volume of 1 FFP = 450 ml 200 ml
389.
Plasma : blood cells = 6 : 4
390.
450ml: 3-4 unit of FFP
391.
Thrombosis & Anticoagulant

392.
In our body, a delicate balance exists between haemostasis and anticoagulation
mechanisms.
393.
Disturbance of this delicate balance will lead to excessive haemorrhage at one
end, or abnormal thrombosis at the other.
394.
Thrombosis- Virchows triad
Stasis stop flowing of blood/ liquid
Hypercoagulability ( thrombotic components)
Damage to endothelium of blood vessels
395.
Acquired risk factors for venous thrombosis
396.
Stasis
397.
Hypercoagulability
398.
Damage to
endothelium
Immobility
Pregnancy and
Trauma and
Hyperviscosity
puerperium
surgery
syndrome
Malignancy
Obesity
Lupus anticoagulant
Oral contraceptive
399.
Mention some risk factors of inherited thrombophilia
(Hypercoagulability)
400.
Established:
Protein C deficiency + clotting factor
Protein S deficiency
Activated protein C resistance (factor V Leiden mutation)
Antithrombin deficiency
Hyperhomocysteinaemia
Elevated prothrombin levels (prothrombin gene mutation G20210A)
401.
Non-established:
Elevated factor VIII level
Plasminogen deficiency
dysfibrinogenaemia
402.
Deep vein thrombosis / Pulmonary embolism
bedside clinical diagnosis - accuracy is only 50%
One must use objective tests to confirm or exclude DVT/PE
Clinical suspect the case start the treatment
Confirm diagnosis by radiological imaging: Ultrasound, primary angiogram
403.
404.
405.
406.
Objective tests required
407.
DVT
408.
PE
409.
Doppler US
412.
Lung scan
410.
+: DVT diagnosed -: refer to
413.
V/Q scan
venogram as false + cannot rule
414.
Pulmonary angiogram
out
(Gold stand, invasive)
411.
Venogram (Gold standard)
415.
CT angiogram
416.
417.
D-dimer in DVT/PE
Screening with less specificity
+ve: extensive DVT/ PE ve: less probable for DVT/ PE
Adv of D-dimer: easily perform
418.
Risk factors for arterial thrombosis
Hyperlipidaemia
Cigarette smoking
Hypertension
Positive family history
Diabetes mellitus
Male sex
Polycythaemia
Anticoagulants are used for the: Prevention and Treatment of thromboembolic

disease
One should know the followings:
Indication
When to start
How? Dosage
Duration
Monitoring
Accepted indications
Deep vein thrombosis (DVT) / Pulmonary embolism
Stroke
Myocardial infarction
Unstable angina
Hemodialysis, heart lung machine Rx: heparin
Atrial fibrillation warfarin in chronic
case
When to start treatment
DVT/PE
Once diagnosis is suspected, start
treatment immediately to prevent
extension
Confirm diagnosis as soon as possible
Dx in the first 24hr complication
D-dimer +ve start the Tx
US for confirm Dx
Antithrombotic therapy
Heparin
Activate antithrombin III, which inactivate the serine protease coagulation factors
(thrombin, Xa, IXa and XIa)
Heparin: faster than warfarin
Heparin as immediate treatment for DVT/ PE, latter switch to use warfarin as which
can be on oral route
Standard Heparin
Heparin + antithrombin III inhibit thrombin
Loading dose 70 units/kg, IV
Maintenance 10-15/kg/hr, IV
Aim at keeping APTT, there is no universal range agree
Upper limit is prefer as reversible
APTT 1.5-2.0 x normal
More sensitive to monitor APTT as normal range of APTT is higher,
percentage is & easily measure
Check APTT 4-6 hours - After maintenance 4 5 half-life of heparin
Low molecular weight heparin (LMW heparin)
LMW heparin + antithrombin III inhibit Factor Xa
Since different preparation, pharmacodynamic of patients
Higher MW heparin cover the whole antithrombin III and inactivate thrombin
Advantages:
Therapeutic effects with recommended dose in most patients
Less bleeding most without signs of bleeding
No need for monitoring side effect and therapeutic effect
Once or twice daily dosing schedule
If monitoring required, monitor Factor Xa
Complications of heparin
Bleeding
Heparin induced thrombocytpopenia with thrombosis (HAT)
70% of unfracturated heparin have thrombocytopenia
Ab against heparin Antithrombin complex consumption of antithrombin,

cause thrombosis
5 days close monitor heparin, however at that moment regimen changed to
warfarin already
Osteoporosis
HAT
Antibodies against heparin + PF4
Activate platelets thrombosis
Usually occurs after 5-7 days of heparin therapy
Must stop heparin immediately
Reversal of heparin effects
Half-life standard heparin 60-90 min.
Protamine sulfate - 1mg per 100 units of heparin in the body
Warfarin
Affect both side (thrombosis, bleeding)
Anti vit K
Net effect depends on the half life, short half life affected first protein C/S
Inhibits Vitamin K dependant clotting factors (II,VII,IX,X)
Also inhibits Vitamin K dependant anticoagulation factors such as Protein C/S
Therefore during active thrombosis never start warfarin treatment without heparin
coverage
Use heparin to control the thrombotic stage first, but in atrial fibrillation case
warfarin first
For DVT/PE
Start heparin when diagnosis is suspected
Confirm diagnosis as soon as possible with objective test
Start warfarin when diagnosis is confirmed
Monitor of Warfarin
Monitor by PT as warfarin affect factor 2, 7, 9, 10 and 7 has short half life
Maintain INR between 2-3
Duration At least 12 weeks for first episode, longest duration is infinite,
commonly 3 to 6 months
Life long for recurrent episodes
INR - international normalized ratio
Tissue thromboplastin + patients plasma Prothrombin Time (PT)
Different thromboplastins have different potencies , eg
Plasma +
PT
thromboplastin A
18
sec.
Same plasma +
PT
thromboplastin B
15
sec.
Same plasma +
PT
thromboplastin C
24
sec.
Since the relative potency of varies tissue thromboplastin is known,
Individual laboratory may use its own thromboplastin, but convert the result as if
the test is performed with thromboplastin A
Why no INR for APTT?
1. LMW heparin does not require monitoring
2. APTT did in lab and does not need to compare result to other lab
Warfarin and Diet
Either ask patients to avoid vitamin K containing food completely OR
No diet restriction as long as they eat a construct mount
Warfarin and drug interaction
Monitor INR whenever a patient is started on a new medication for > 1 week or a

regular medication is stopped

Warfarin side effects
On pregnancy
S/E
1st
ter
Bleeding
trim
ato
Warfarin
ester
gen
sensitivity
ic

2nd
trim
ester
3rd
ble
trim
edi
ester
ng
Reversal of Warfarin effects
Vitamin K
FFP
Over-warfarinization
Most important: stop warfarin
Assess if patient has active bleeding
Resuscitation and transfusion if haemodynamically unstable
Reversal of anticoagulation if there is major bleeding:
Vitamin K
Fresh frozen plasma
Prothrombin Complex Concentrate
Warfarin indicated for patients with
Prosthetic valves
Rheumatic heart disease with atrial fibrillation
Mural thrombi
patient with chronic atrial fibrillation
Risk factors for arterial thrombosis (Stroke, TIA, Ischemic heart disease)
Hyperlipidaemia
Hypertension
Diabetes mellitus
Polycythaemia
Cigarette smoking
Positive family history
Male sex

 Antiplatelet Agent
Useful for:
TIA
Stroke
Ischemic heart disease (unstable angina , MI)
Aspirin
Inactivates COX activity platelet
Prevention of TXA2 synthesis
Impairment of platelet aggregation
Thienopyridines
Ticlopidine and clopidogrel
Inihibit ADP induced platelet aggregation
Glycoprotein IIb/IIIa receptor antagonists
Abciximab, epitifibatide, tirofiban
Inhibit the final common pathway of platelet aggregation

LMWH
Stroke
Ischemic heart disease (unstable angina , MI)
Stroke cerebral infarction, haemorhage excluded
? LWM heparin - beneficial for recent infarct
Aspirin for TIA
?
? synergistic effects
Warf
with aspirin
arin
?
clopi
dogr
el
Unstable angina
Aspirin
LMWH
Thrombolytic therapy
Fibrinolytic agents (Streptoinase, Urokinase, t-PA)
Enhancing the conversion of plasminogen to plasmin, which degrade fibrin.
They are used to lyse fresh thrombi
Facilitate rapid restoration of vascular patency
Recent MI, Stroke
? Massive PE

 Cytopenia
Production
BM hematopoiesis
affects all the blood
cells production

Destruction

Circulation/
RE system
Many about
spleen
Premature
death

Abnormal blood counts

R
Anemia
B
C
P
Thrombocytopenia
l
a
t
e
l
e
t
W
Leucopenia
B
Classified as cell types
C
involved:
Neutropenia
Lymphopenia
monocytopenia

Sequestration
Compartmentalization, Stay in
spleen & not go to other place/
circulation

Erythrocytosis
Thrombocytosis

Leucocytosis
Classified as cell types involved:
Neutrophilia
Lymphocytosis
Monocytosis
Eosinophilia
Basophilia

Erythr
Blood becomes thick thrombosis
ocyto
sis
Lymp
In viral infection & chronic infection
hocyt
osis
Monoc
In chronic infection
ytosis
Neutr
In bacterial infection
ophili
a
Eosin
Parasite, hypersensitivity
ophili
a
Basop
Uncommon for reactive, need to rule out blood
hilia
malignancy - CML
Stem cells commitment
Erythro
RBC
poiesis
Granulo
Neutrophils, monocytes, basophils,
poiesis
eosinophils
Thromb
Platelets
opoiesi

s
Lympho
T, B lymphocytes, cytotoxic T cell
poiesis
viral infection
Growth factors
Erythrop
EPO produced in kidney, can be used as
oietin
drug to Tx anemia
Granulop
G-CSF, GM-CSF, M-CSF improve WBC
oietin
comes out, G-CSF mobilize stem cells for
resure BM failure
Thrombo
TPO, improve immunocompromised
poietin
patients
Production problem can be divided into 4 categories
Empty
Aplastic
All blood cells affected, anemia is
factor
just one sign
y
Raw
Fe, B12,folate
Important for general DNA
materi
synthesis
al
Fe deficiency large MCV, Hb
Ineffe
Myelodysplastic
Cannot produce mature cells to
ctive
circulation
Infiltra
Myeloma, lymphoma,
TB force BM out
tive
cancer, granuloma

Cytopenia
Pancytopenia - in all
blood cells
Isolated cytopenia

Trilineage/ Bilineage cytopenia

Anemia
Thromobocytopenia esp. in pedi
Leucopenia - neutropenia
Causes of Pencytopenia: 70-80% due to production problem, as destruction
affects one cell type commonly
Aplastic anaemia
Megaloblastic anaemia
Leukaemia, MDS, Myelomatosis
Bone marrow infiltration
Myelofibrosis
Hypersplenism peripheral cause, spleen stay, spleen secrete &
destruction
Autoimmune disorders (SLE) combine cause
Paroxysmal nocturnal haemoglobinuria
Cytotoxic chemotherapy most common cause
In thalassemia, recruit retired BM for production
Pancytopenia with production cause
More commonly problems of Production than Consumption/Destruction
More implication on BM failure
Primary BM disorder
Secondary BM disorders
Aplastic anaemia (Marrow with fat)
Carcinoma
Acute leukemia (Marrow with
TB granuloma
leukemic blasts)
Myeloma
Myelofibrosis (Marrow with
Lymphoma
fibroblasts)
Neuroblastoma
Myelodysplastic syndromes (active
Storage disease

but ineffective marrow)

Problem with maturation

Gelatinous transformation: Change of

marrow characterized by atrophy of
fat cells and hematopoietic cells and
accumulation of serous fluid in the
interstitium

Aplastic Anemia
Hypoplastic anameia:
Bone marrow failure
Pancytopenia:
anaemia, leucopenia (by opportunistic infection) and thrombocytopenia
resulting from the aplasia of bone marrow

Primary
Secondary
Congenital
Industrial (Benzene, Insecticide)
(Fanconis anaemia)
Post-viral infection, 6-9 mths before
Acquired
iatrogenic (Cytotoxics)
(Idiopathic)
Hypersensitivity (Chloramphenicol eye drops, gold,
sulphonamide, phenylbutazone)
Pathogenesis:
Substantial reduction in the number of haemopoietic pluripotential stem cells
Stem cell defects or immune reaction against the stem cells
Inability to divide and differentiate to populate the bone marrow
Diagnosis
CBC
Peripheral smear
Bone marrow study
No abnormal cells
Hypocellular/Hypopla
Hb, Normal or MCV

sia (bone marrow

(most time)
biopsy mandatory)
Retic

Confirmatory test
WBC

Platelets
Hypoplastic bone marrow
Biopsy

Normal

 Aspirate

Normal cellularity about

50%
Aplastic: 5%

Congenital aplastic anaemia: Fanconi anaemia

Recessive pattern of inheritance
Growth retardation and congenital defects of the skeleton (Microcephaly, absent
radi or thumbs), of renal tract (pelvic or horseshoe kidneys) or skin (areas of
hypo- or hyper-pigmentation) and mental retardation
Develop AML (10%)
Dx: Increased random chromosomal breaks
Tx: androgens and or BMT
Acquired aplastic anameia
Probably autoimmune in origin: Patients T lymphocytes suppress the
hematopoietic stem cells
Secondary:Ionizing radiation, Chemicals (benzene), Cytotoxics,
Chloramphenicol, Gold etc and infections (post-hepatitis A)
Tx: ATG, cyclosporin, HD methylprednisolone,
androgens and BMT
Myelofibrosis (chronic blood cancer)
Primary: hematological malignancy
Reactive: In response to marrow infiltration and
irritation (carcinomatous infiltration) (look hard for
cancer cell)
BM failure
Leucoerythroblastic picture (immature blood cells in
blood): Sign of BM irritation or infiltration with blasts,
nucleated RBCs, myelocytes in PB (Cells from BM
seen in PB)
Tear drop cells are characteristic
Investigation:
Unexplained pancytopenia always requires BM
examination with aspiration smears and trephine
biopsy to evaluate possibility of aplastic anaemia,
acute leukemia and infiltration (TB or hidden
carcinoma)

Tear
drop
cells

Rule out chemotherapy cause

Can evaluate Production status
BM biopsy for cell architecture, cellularity, infiltration
DDx:
Aplastic anaemia: Good length of biopsy to confirm cellularity.
Acute leukemia: Good aspiration smears+ BM blood for immunophenotyping
Infiltration: Good trephine biopsy for evaluation of infiltration + ZN/Fungal etc
special stains

Isolated cytopenia - Production

Pure Red Cell Aplasia: Congenital (DBS)
or acquired (Pavovirus B19/ thymoma/
Autoimmune disease), damage RBC
progenitor cells
Pure Amegakaryocytic
thrombocytopenia: Rare congenital (TAR)
or acquired (pre-MDS or AML)
Agranulocytosis: Hypersensitivity
reaction with selective damage of
granulocytic precursors in BM by drugs (e.g.
anti-thyroid, anticonvulsants, gold)
Causes of Red cell aplasia
Congenital
Acquired
Diamond-Blackfan
Chronic:
Syndrome
idiopathic
associated with thymoma and lymphoma
Acute (transient):
parvovirus
other infections
drugs
riboflavin deficiency
Thrombocytopenia with absent radii (TAR)
syndrome: Rare congenital problem
Lymphopenia:
AIDS
Congenital immunodeficiency syndrome
B/T cell deficiency
Monocytopenia:
Hairy cell leukemia (chronic cancer)
Neutropenia:
Neutrophils <2.5 x109/L
Neutrophils <1 risk of infection

Neutrophils <0.5 likely recurrent

infections
Neutrophils <0.2 serious fatal infection
EXAM!! Important to know them!!
Cancer patients on chemotherapy
BM failure patients [pancytopenia]
Congenital: Kostmans syndrome, AR
Drugs: Chloramphenicol, Gold,
antithyroid, phenytoin etc
Immune: SLE (Production and
Destruction)
Infection: HIV, MTB
Ix: opportunistic infection w/ Candida albicans
Pancytopenia - destruction
More often isolated (single lineage) cytopenia or bilineage
cytopenia
Hypersplenism: RE destruction and splenic pooling
PNH: Complement sensitivity of blood cells-causes lysis
Autoimmune disorders: SLE (rarely trilineage cytopenia)
causes peripheral destruction
Paroxysmal nocturnal haemoglobinuria
Clonal stem cell disorder
Intravascular hemolysis
Acquired defects of red cells: membrane highly susceptible to complement lysis
WBC and PLT may also decrease with dangerous thrombosis
Lack of glyceryl phosphatidyly inositol (GPI): anchor of CD55 and CD59
(protective factors)
Acquired aplastic anaemia
Dx: Positive detection of
CD55/CD59 deficient blood cells
by flow cytometry BM studies:
Hypoplastic marrow
Left is over-night urine sample,
very dark

Isolated cytopenia - Lineage restricted destruction

Immune destruction: Autoimmune
Mechanical destruction: Heart valves
disorder Vs Alloimmune
(RBCs)
RBC: Common (Hemolytic anaemia)
Infection: Malaria, Typhoid fever
WBC: Uncommon (Neutropenia)
(WBCs)
PLT: Common in Children (ITP)
Drug induced

 Hematological Malignacies

The leukemia cells look appear to normal cells, morphologically indifferent.

Different on count, normal value not > 5%
Myelocytes promyelocytes metamyelocytes neutrophils
Spectrum of Hematological Malignancies
Acute Leukemias (AL)
Acute Myeloid Leukemia (AML)
Acute Lymphoid Leukemia (ALL)
Myelodysplastic Syndromes (MDS)
Chronic Myeloproliferative Diseases
Chronic Myeloid Leukemia (CML)
(CMD)
Polycythemia Vera (PV)
Essential Thrombocytosis (ET)
Myelofibrosis (MF)
Lymphoproliferative Disorders (LPD)
Malignant lymphoma (ML)
HD
NHL
Multiple Myeloma (MM)

MDS: ineffective on production, pre-leukemia stage

PV: patients Hb appear red
ET: platelet
MF: induced by cancer infiltrate, primary form
MM: B-cell problem
Leukemia
Leukemic cells morphologically resemble normal precursor cells (blasts) and
mature hematological cells (myelocytes, neutrophils and lymphocytes)
Normal Bone Marrow

Metamyelocyte,
nucleus change
Earliest
immature stage

Chromatin
Promyelocytes
larger than mast
cells
Granules are
myloperoxidase
N/C ratio can be recognized
Nucleone = immature
Leukemia
Malignancies of lymphoid precursor Acute Lymphoblastic Leukemia (ALL)
B- and T- cell
blasts in PB and BM (>30%), excess
basal
Malignancies of myeloid precursor
Acute myeloid leukemia (AML)
cell
blasts in PB and BM (>20%)

 Malignancies of clonal
hematopoietic stem cell
Malignancies of mature B or T cell

CMPD can develop to ALL/AML,

MDS
LPD already in mature cell
transform at stem cell level, ML
Lymphoid and myeloid are differentiated by enzyme profile. Myeloid has CD 3/10
while lymphoid have other CD.
B-cell and T-cell have different antigen profile
Malignant proliferation and accumulation of leukemic blasts in the bone marrow.
Rapidly fatal if untreated, for non-acute patient, the patients can live longer
These blast cells may cause bone marrow failure and circulate in the blood and
infiltrate organs, staging starts on circulation, so it does not count as metastasis
Features: Bone marrow failure, leucocytosis (some with leucopenia) and organ
involvement: liver, spleen, LNs, skin, brain, testes hence male have worse
prognosis as testes can provide place for the cancer
80% of Children: ALL 80% of Adults: AML
Signs and Symptoms
Related to bone marrow failure- pancytopenia
anemia, infection, bleeding.
anemia anemic symptoms
Opportunistic infection cause fatal fungal
septicemia
Pancytopenia is due to lack of function blood
cells
Bone pain due to bone marrow expansion, like
infilatrate to bone
Leukemic infiltration- reticuloendothelial system (LN,
hepatosplenomegaly), CNS, Testis, Gums Skin etc.
(AMLM4)
P/E on CNS, Testis and gums
Gum hypertrophy in M4, M5
Rapid cell turnover- Metabolic disturbance: Uric acid,
LDH etc
uric acid: RF, gout
LDH in hemolytic anemia (but not just it), at very
high level
Diagnosis
CBC: Low Hb but Raised white cell count up to 200
x109/L (Normal 4-11), many blasts and low platelet count [Leukemic
leukemia and aleukemic leukemia]
WBC as blast cells are counted as WBC
Aleukemic: WBC not as stay in BM
Diagnosis: Bone marrow examination:blasts > threshold
Classification: Morphology, Immunophenotyping (Flow cytometry),
Cytochemistry and Cytogenetics (MICC)
Morphology: monocytic & auer rod: M3
Cytochemistry: stain enzyme, granules in ALL - myeloperoxidase
Cytogenetics: t(15;17) confirms M3, diagnostic role; t(9;22), t(4;11) indicate
poor prognosis patients need transplantation for cure
Molecular studies for gene rearrangements: Sensitive, Specific and Fast
Growth cells: 1-2 week but molecular studies 2 days can get the result
Complete Blood Report of Aleukemic leukemia
Besides MCV, MCHC & MCH are normal, others
Reticulocytes 1% - more likely a production problem

Many blast cells (written on report) have BM exam to see whether there is any
infiltration
Classification of ALL
B-lineage: B-lymphoblastic (more common), maturation in descending order
Early precursor B (Pro-B) ALL
Common ALL (Calla/CD10 + ALL; hyperdiploidy more than 46 chromosomes)
Gd news for child but not adult, better prognosis for children
Pre-B ALL (cytoplasmic +; t(1;19))
Mature B ALL (Burkitts aggressive, t(8;14))
T-lineage: T-lymphoblastic
FAB classification : L1, L2, L3 (Mature B ALL).
Cytogenetics: t(4;11), t(9;22): prognostically poor
Classification of AML

Undifferentiated,
SBB/MPO(myeloperoxidase)-

90% blasts in BM

Undifferentiated, SBB/MPO+

90% blasts in BM

With maturation: with variable

numbers of maturing cells

20% blasts in BMt(8;21)

more important, see
maturation

Acute promyelocytic
Hypergranular; Multiple Auer
rods (Faggots)

t(15,17); PML-RARA

Microgranular variant

t(15,17); PML-RARA

Specific Tx: ATRA, Arsenic

Specific Tx: ATRA, Arsenic

Acute myelomonocytic

t(4;11) in infantile leukemia,

infant group with poor
prognosis

With eosinophilia (abnormal

purple-violet granules)

Inv chromosome 16
CBF/MYH11);

Acute monoblastic

Infiltrations: Gum, soft tissues

Acute monocytic

Infiltrations: Gum, soft tissues

Acute erythroleukemia

Erythroid abnormalities

Acute megakaryocytic cell

budding

Infantile t(1;22), Down

syndrome

M3: Medical emergency, delay patients may dead by DIC

M4: gum hypertrophy, more neutrophils
ATRA: induce apoptosis and differentiation
Treatment without ATRA: release of necrosis cell content, patient dead by DIC
PML from 15, RARA from 17
AML-M3 [Acute Promyelocytic Leukemia
(APL)]
High risk of bleeding and rapid death
Urgent diagnosis required
>30% of abnormal promyelocytes in the BM
Heavy, dense granulation & abundant Auer rods,
sometimes forming bundles
Often associated with disseminated intravascular
coagulopathy (DIC)
Typical t(15:17) translocation involving the retinoic
acid alpha receptor gene on 17q21 and the PML
gene on 15q22
Diagnosis
Blood smear
Chromosomal study
PCR
Hypergranular cells
t(15;17)
PML-RARA
cause DIC
rearrangement
Auer rods and Faggot
quick way to do it
cells
Treatment:
ATRA induce apoptosis and differentiation, avoid necrosis causing DIC
All trans-retinoic acid therapy
Arsenic therapy, 2nd line therapy
Conventional cytotoxic chemotherapy, when DIC under control
Good prognosis if treated properly
Normal eosinophils have red, fine granules

Budding: characteristic of
AML M7
Budding production of
platelets

Presence of vacuole in
leukemic cells
Poor prognosis and
aggressive

Acute leukemia: Treatment

Supportive: blood transfusion, platelet transfusion, antibiotics

No WBC transfusion as which contain many germs

Antibiotics for prophylactic use
Specific: Cytotoxics, radiotherapy +/- BMT
Antiemetics as chemotherapy induce vomiting
Isolation & Good nursing care
Close monitoring
Good prognosis for childhood ALL
Poor prognosis for adult acute leukemia
Chronic Myeloproliferative Diseases (CMPD)
Clonal haemopoietic stem cell disorders characterized by proliferation in the
bone marrow (BM) of one or more of the myeloid (i.e., granulocytic, erythroid
and megakaryocytic) lineages resulting in increase in peripheral counts of one
or more lineages (RBC, WBC or PLT)
The mature cells are sub-normal

Philadelphia
chromosome is
detected by
cytology/ molecular
basis.
PV:
The Hb is about 2x
than normal
Either one or 2
parameters in blood
report have problem
MF:
count as
proliferates
count as postfibrotic
JAK2 mutation
confirm Dx of MPD,
CMPD but not CDL

Distinguish between Cytosis and Cythemia

RBC - erythrocytosis vs erythemia
WBC - leucocytosis vs leukemia
Plt - thrombocytosis vs thrombocythemia
Cytosis
Cythemia
increase
implies the increase is due to Primary Bone Marrow Disorder
in
(malignancies)
counts,
Hyperviscosity ( red and white blood cells, blood diff to flow
reactive
ischemia)
Thrombosis ( blood cells; flow)
Hepatosplenomegaly (heavy infiltration)
Reactive erythrocytosis for Hb:
Kidneys are important to sense hypoxia

 Paraneoplastic
syndrome:
Cancer cells
secrete atopic
hormone

Reactive
thrombocytosis
for Plt:
produce more
platelet to plug the
hole

Diagnosis and
treatment of
CMPD
Diagnosis:
After excluding reactive (eg infection)/secondary causes of leucocytosis and
thrombocytosis, consider CMPD
Perform bone marrow (hypercellularity or fibrosis) and cytogenetic studies (for Ph
chromosome status)
Treatment:
Venesection (cut out vein): (Apheresis procedure - WBC)
Chemotherapy: Cytotoxic drug (Alkylating agents, P32 etc); antiplatelet drugs (ET)
Chronic myeloid leukemia: clinical features
Adult male more common
Hypermetabolism: night sweats, weight loss, anorexia (DDX: thyrotoxicosis)
Massive splenomegaly: abdominal distension and discomfort
DDx: CML, Myelofibrosis
Symptoms of low Hb and platelet count
Gout: hyperuricaemia
Hyperviscosity syndrome: Hearing and visual disturbance; angina; claudication
(impairment in walking), Priapism (erect penis)
Investigation and Treatment
Laboratory: WBC 50-200 x 109/L (DDx: leukemoid reaction severe
sepsis
Blood film: a spectrum of granulocytic cells as come to peripheral blood
Cytogenetic analysis on BM: t(9;22) [Ph chromosome]
BM: Hypercellular and granulocytic hyperplasia
Neutrophil alkaline phophatase score (NAP) low
Tx of CML: Leucopheresis; Hydroxyurea; tyrosine kinase inhibitor
(Glivec) for inhibit BCL gene; -IFN;
BMT (allogeneic): Alternative when TKI fails
Triphasic CML
Chronic phase: Extreme leucocytosis with largely mature and a few immature
forms and marked splenomegaly
Accelerated phase: increasing blast count and splenomegaly

 Acute phase: Transformation to Acute leukemia (AML or ALL)

Pathogenesis:
Normal bone marrow cells replaced by cells with Philadelphia chromosome
[abnormal chromosome 22 resulted from t(9;22)]
Fusion of oncogenes: BCR-ABL rearrangement: an acquired abnormality of
haemopoiectic stem cells that is present in all dividing granulocytic, erythroid
and megakaryocytic cells in the marrow

 Myelodysplastic syndrome (MDS)

MDS can
transform to
AML
For elderly
patient with
AML, no
treatment and
palliative
instead

Chronic lymphocytic
leukemia
Elderly >40 y.o.
Lymphoadenopathy,
splenomegaly at late stages
Lymphocytosis:
monoclonal B cell
proliferation
Susceptibility to infection (e.g.
herpes zoster)
Low Hb and platelet count at
late stages: bone marrow
infiltration
Autoimmune hemolytic
anameia or thrombocytopenia
(Ab against blood cells and platelet)
Dx: CBC, blood film and immunophenotyping
Tx: No treatment, Steroid, Combination
chemotherapy, monoclonal antibodies
Malignant lymphoma
Hodgkin and non-Hodgkin lymphomas
Malignant disease of the lymphoreticular system
with monoclonal lymphoid proliferation in LN,
Spleen, Liver
Nodal disease: LN (Hodgkin lymphoma): Reed
Sternberg cells
Extranodal: stomach, GI tract, brain etc (NHL)
Clinical features: LN enlargement with fever
Dx: LN section (a spectrum of cellular and histological morphology)
Tx: Combination chemotherapy

Myeloma

Mature
lymphoc
ytes

Sme
ar
cells

1.
2.
3.

Clonal B-cell derived plasma cell

malignancy
Plasma cell proliferation that
infiltrates bone marrow and secretes
a paraprotein (IgG or IgA) with light
chain ( or ) restriction
Osteolytic lesions: Bone pain
Protein electrophoresis: monoclonal Ig
peak with suppression of normal Ig
(immunoparesis): prone to infection
Hyperviscosity syndrome: visual
disturbance
Biochemical abnormality
Multiple myeloma: serum protein
electrophoresis. A monoclonal M protein in the region
and background decrease of and globulins is present.
This deficiency and the spike of M protein (monoclonal
gammopathy) are typical of MM.
Dx:
Bone marrow examination: >30% plasma cells
Biochemistry: Serum paraprotein IgG/IgA increased
(monoclonal Ab)
Skeletal survey (X-ray of bones): Osteolytic lesions
Tx: Chemotherapy, RT, -IFN, ASCT, Thalidomide,
proteosome inhibitors

 Lymphoma

1.
2.

Lymphomas are a heterogeneous group of diseases caused by malignant

lymphocytes.
The diseases can either be nodal (tumor cells accumulating in lymph nodes) or
extranodal (tumor cells infiltrating organs outside the lymphoid tissue, e.g.
stomach, thyroid, even skin)
Occasionally tumor cells may spill over into blood (leukaemic phase, like
leukemia but uncommon)
Classification
Lymphomas can be divided into Hodgkins disease (lymphoma) and nonHodgkins lymphomas based on the histological presence of Reed-Sternberg
(RS) cells in Hodgkins lymphoma
WHO classification: Stratified neoplasms primarily according to lineage.
Within each category, distinct diseases are defined according to a combination of
morphology, immunophenotype, genetic features and clinical syndromes
Hodgkins lymphoma
Pathology
Lymphoid
Characterised by presence of
Neoplasms
Reed-Sternberg (RS) cells, which
is of B-lymphoid lineage.
Hodgkin's
Non-Hodgkin's
Epstein-Barr virus (EBV) genome
Lymphoma
Lymphoma
detected in ~ 50% of cases
Peak incidence 3rd decade and
B cell
T and NK cell
the elderly
neoplasms
neoplasms
Clinical features
Present with painless, non-tender, asymmetrical, firm, discrete and rubbery
enlargement of superficial lymph nodes.
Cervical lymph nodes involved in 60-70% of cases.
Clinical splenomegaly (not massive) in 50% of patients
Diagnosis
Histological diagnosis
Reed-Sternberg cells multinucleate, with a characteristic owl eye appearance
Associated with reactive inflammatory components consisting of lymphocytes,
eosinophils, plasma cells and histiocytes
Reed-Sternberg cells
Larger than lymphocytes
More than 1 nucleus
Prominent of nucleolus
Histological classification
Nodular lymphocyte predominant Hodgkins
lymphoma
Classical Hodgkins lymphoma
A. Nodular sclerosing
B. Mixed cellularity
C. Lymphocyte-rich
D. Lymphocyte-depleted
Nodular sclerosis and mixed cellularity types are more frequent

Most favorable prognosis

lymphocyte predominant
Nodular sclerosis type
predominates in young adults;
the other types have a bimodal
age distribution.
Mediastinal involvement is a
feature of nodular sclerosis type,
particularly in young women.
There may be associated pleural
effusion or superior vena cava
obstruction
Clinical Staging
Ann Arbor scheme
Stage I to IV
A or B, indication absence (A) or
presence (B) of constitutional features:
unexplained fever >38C, night sweats, or loss of >10% of body weight within
6 months
Localized extranodal extension from a mass of nodes which does not advance the
stage indicated by subscript E
Treatment & prognosis
Radiotherapy, chemotherapy, or combination of both.
5-year survival - 50% to >90%; depending on age, stage and histology.
Treatment related complications:
myelodysplasia, AML, sterility, intestinal complications, myocardial infarction
and other cardiac and pulmonary complications
Non-Hodgkins Lymphoma
More variable in clinical presentation and natural history than Hodgkins
lymphomas
Predisposing factor
HTLV-1 adult T cell leukaemia/lymphoma.
Epstein-Barr virus post-transplant lymphoproliferative disease, Burkitts
lymphoma, NK/T cell lymphoma
Helicobacter infection mucosa-associated lymphoid tissue (MALT) lymphomas of
stomach
Inherited or acquired immunodeficiency predisposes to B-cell lymphomas (high to
intermediate, B-cell origin)
Increased incidence of lymphomas at unusual sites in AIDS patients. The
lymphomas are usually of B-cell origin and of high grade or intermediate grade.
Hepatitis C infection has also been suggested as a risk factor of NHL
Histological grading
Clinician has subdivided NHL into low grade and high grade, with some falling
into an intermediate grade.
Low grade NHL
High grade NHL
relatively indolent, respond well to
aggressive and need urgent
chemotherapy and are very difficult
treatment but are often curable
to cure
Clinical features
Superficial lymphadenopathy.
Constitutional symptoms less frequent than in Hodgkins lymphomas and their
presence is usually associated with disseminated disease.
Anemia, neutropenia with infections or thrombocytopenia with purpura may be
the presenting symptoms with diffuse bone marrow involvement

Abdominal disease liver and spleen are often enlarged and involvement of
retroperitoneal or mesenteric lymph nodes are frequent
Extranodal lymphomas
Gastrointestinal tract is the most common extranodal site
Skin, brain, testis and thyroid involvement not infrequent
Skin is primarily involved in two unusual closely related T-cell lymphomas: mycosis
fungoides and Szary syndrome
Immunological markers
Cluster differentiation (CD)
Monoclonal antibodies to antigens
expressed on cells at
sequential stages of lymphoid development and in different lineage or states of
activation
Useful in the classification of NHL, differentiate the lineage
T-cell CD3, CD5, CD7
T-cell subsets CD4, CD8
B-cell CD19, CD20, CD22, CD24
Leucocytes common antigen CD45
MIB1
In M1B1: proliferation & mitotic
Cytogenetic findings
Various subtypes of NHL are associated with characteristic chromosomal
translocations which are of diagnostic and prognostic value.
Burkitts lymphoma : t(8;14)
Follicular lymphoma : t(14;18)
Mantle cell lymphoma : t(11;14)
Anaplastic large cell lymphoma : t(2;5)
Gene rearrangements
Useful in diagnosis and classification of NHL especially in difficult cases.
B-cell lymphomas clonal rearrangement of immunoglobulin (Ig) genes, usually
involving both heavy and light chain genes.
T-cell lymphomas clonal rearrangement of T-cell receptor (TCR) genes
Investigation of NHL
Lymph node biopsy (excisional biopsy, trucut biopsy [may have sampling error])
definitive investigation
Morphological examination +/- immunophenotypic analysis +/- genetic analysis
Suspected peripheral T-cell lymphoma
Trephine biopsy of
marrow may be valuable.
Serum LDH level
frequently raised. Useful as a
prognostic indicator and for monitoring response to treatment.
Immunoglobulin electrophoresis may reveal a paraprotein
Staging of NHL
Ann Arbor Scheme.
Less clearly related than histological types to prognosis.
Chest X-ray, CT scanning, MRI, PET scan for multiple regional LN involvement

IHC

CD3

H&E

Positron-emission tomography (PET) may

detect disease not seen on CT scan and
useful for following treatment response.
Follicular lymphoma
Most common form of NHL.
Middle aged or elderly.
Characterized by a benign course for many
years.
Follicular pattern (neoplastic follicles).
Bcl-2 overexpression
Bcl-2 stain for Dx
Extranodal marginal zone B-cell
lymphoma of mucosa-associated
lymphoid tissue (MALT lymphoma)
Most common site stomach.
Other sites other part of gastrointestinal
tract, lung, head and neck, ocular adnexae,
skin, thyroid, breast.
Associated with pre-existing inflammatory or
autoimmune disease Helicobacter pylori
associated chronic gastritis, Sjogren syndrome,
Hashimotos thyroiditis.
Indolent natural course.
Centrocyte-like cells, lymphoepithelial lesions,
lymphoid follicles, not neoplastic
Protracted remissions may be induced in H.
pylori associated gastric MALT lymphoma by
antibiotic therapy for H. pylori
Burkitts lymphoma (B-cell
lymphoma)
Highly aggressive, high grade
Three clinical variants: endemic
(African), sporadic, immunodeficiency
associated.
Associated with EBV infection.
Jaws and other facial bones (orbit) as
site of presentation in ~50% of endemic
Burkitts lymphoma.
Histological feature: Starry sky pattern
Oncological emergency, immediate treatment
as easily electrolyte imbalance
Diffuse large B-cell lymphoma
Classical high grade lymphoma.
Nodal or extranodal.
De novo or present progression /
transformation from a less aggressive
lymphoma.
Large neoplastic B lymphoid cells, lager than
RBC
Aggressive but potentially curable with
multiagent chemotherapy, potential curable
Mycosis fungoides and Sezary syndrome

Mycosis fungoides is a chronic cutaneous Tcell lymphoma.

Epidermal and dermal infiltration of
neoplastic T-cells with cerebriform nuclei,
irregular nuclei, like cerebrum without sulcus
T-cell lymphoma involved skin, infiltrate
dermis, epidermis
Sezary syndrome: generalized disease
characterized by erythroderma,
lymphadenopathy and neoplastic T
lymphocytes in blood.
More aggressive
Extranodal NK/ T-cell lymphoma, nasal
type
Also known as lethal midline granuloma.
More prevalent in Asia, Mexico and
Central and South American, relative
common in HK
Extranodal. Nasal cavity as the
commonest and prototypic site of
involvement.
Constantly associated with EBV.
Angiocentric and angiodestructive