Disorder Classification Defect (in)

Ankyrin
Mutations in band 3 or
4.2 may also cause it
Unable to maintain
Hereditary Hereditary (AD) normal shape MCHC
Spherocytosis membrane defects increased

mutation in
Paroxysmal Nocturnal Acquired membrane phosphatidylinositol
Hemoglobinurea defect glycan A
Lack glucose-6-
phosphate
dehydrogenase
Cannot produce GSH to
protect cell from
oxidative stress Patient
suddenly turns yellow
Hereditary (XR) from Oxidative drugs -->
G6PD deficiency metabolic defect sudden anemia

Pyruvate Kinase Hereditary (AR)

Deficiency metabolic defect Impaired ATP synthesis
 beta globin chain has
substitution at position 6
G6V mutation in b-chain
Homozygous = disease,
heterozygous = trait
Many other mutations:
Hemoglobin C is another
Hemoglobin S (Sickle Hereditary (AS) variant (milder in
Cell) qualitative Hb defect symptoms)

Hereditary quantitative
a - Thalassemia Hb defect β-thalassemia major:
Homozygous or
compound heterozygous
(β0/β0, β0/β+, or β+/β+)
β-thalassemia trait: β/β+
or β/β0
Mostly due to gene
deletions or
transcription/translation
Hereditary quantitative Hb decreased but Iron
β - Thalassemia Hb defect level increased

synthetic valves or
Mechanically induced microangiopathic
anemia disease
 IgG anti-RBC that react
Warm AIHA Immune mediated optimally at 37°C

IgM anti-RBC that react

Cold AIHA Immune mediated optimally at 0 – 4°C

Cold Hemolysin IgG anti-RBC that react

Hemolytic Anemia Immune mediated optimally at cold temp,

Drug Induced Immune

Hemolytic Immune mediated
Alloimmune Hemolytic Immune mediated incompatible blood types

Malaria

Chronic Renal Failure

Lead Poisoning Impaired production heme synthesis

Iron deficiency Impaired production heme synthesis

Anemia of Chronic
Disease Impaired production heme synthesis

B12 deficiency (other

causes) Impaired production DNA synthesis

Pernicious Anemia Impaired production DNA synthesis

Folate Deficiency Impaired production DNA synthesis

Reduced proliferation of
stem cells or produce
Aplastic anemia Impaired production neo-antigenic progeny

Myelophthisic anemia Impaired production Bone Marrow

Erythrocytosis Erythrocyte ++ EPO, or malignant

(Polycythemia Vera) overproduction stem cells
Pathogenesis Severity Cell morphology &Labs

1. Shear stress slowly

cause loss of
membrane.RBC's
become rounded
due to low surface area Normocytic
to volume ratio. sperical cells
2. Extravascular Howell Jolly bodies
hemolysis of inflexible (small dark nuclear
spherocytes in the mild to moderate (6 – 9 remnant), MCHC
splenic cords d/dL) Increased
1. GPI anchor is NOT
synthesized
2. CD 59, 55 (DAF), C8
binding proteins not
available on cell
1. Exposureno
membrane; to oxidative
stress
protection from
2-3 day lagcomplement
alternative period. then:
2. Initially
pathway Intravascular Low platelet count
lysis of severly damaged
cells
3. But ultimately
accumulation of Heinz
bodies & membrane by Normocytic
macros leads to “bite cells”
Extravascular A- in American blacks Spherocytes may be
sequestration (some function) present Heinz bodies
(moderately damaged A0 in mediterranian RBC with precipitated
cells). variant (zero function) denatured globin

1. low ATP
2. dehydration & change
in morphology
3. Extravascular echinocytes (RBCs w/
hemolysis thorny projections)
1. Deoxygenated Hb's
aggregate in cell. So
hypoxia causes sickling.
2. Microvascular
damage & tissue
ischemia as sickled cells Severe (3 – 8 g Hb/dL)
aggregate & plug Symptoms develop Anisocytosis &
vessles around age 6 months poikilocytosis.
3. Extravascular (when HbF is (Ir)reversibly sickled
hymolysis diminished) cells

1. a-chains aggregate
into tetramers making
abnormal Hb. Ineffective microcytosis
Oxygen transport Hypochromia
2. membrance damage Major: severe Anisocytosis
leads to Extravascular Trait: asymptomatic/mild Poikilocytosis
1. RBCs damaged by
hemolysis anemia Target cells
passing through fibrin
cords or synthetic
valves. Also seen
Microangiopathic
(narrowed vessels) w/
TTP, HUS & DIC
2. Results in
Intravascular hemolysis Etiology is more
& production of significant that the actual Schistiocytes:
schistiocytes anemia fragmented RBCs
1. cause: Idiopathic or
secondary to
autmimmune diseases,
Primary cause idiopathic
Lymphoma/leukemias or
secondary cause
other neoplasms. Or -
infection and
drug induced.
Waldenstrom
2. Abs bind to RBCs at
macroglobulinemia 1.
body temp (Type II HSR)
cause: acute
3. Extravascularphase Spherocytes formed due
assoc. w/ infestions:
hemolysis - Autoab Can be sever & life to splenic macros
EBV/mycoplasma.
signals spleen to rid of threatening (4 – 6 g plucking Ab bound cell
Chronic:
RBC idiopathic or Hb/dL) membrane
assoc. w/ CLL,
macroglobulinemia,
diffuse large B
cell lymphoma & splenic
lymphoma.
2. Abs bind to RBCs
when blood is cooled
(e.g. at extremities)
3. cryocyanosis of mild to moderate stable
extremities anemia agglutination of RBCs

1. exposire to cold
2. Abs attach to P Ag on
RBC
3. complement mediated
Intravascular hemolysis
when RBC
recirculates to warm
area
1. Introduction of depends on prior
immunogenic RBCs sensitization to Rh
2. IgM mediated factor, and dose of blood
Intravascular hemolysis exposed

1. inhibits ala
dehydrogenase and
ferrochelatase microcytic Hypochromic
2. impaired Hb synthesis Cells
 variety of cell sizes;
starts as normocytic –
progresses to microcytic
varies Hypochromia
1. presenece of a
chronic illenss (infection,
autoimmune disorder, or
malignancie); increases
hepcidin
1.
2. Malabsorption
hepcidin prevents due to
terminal
transfer ofileum
iron diseases
from Initially normocytic –
(Celiac, Chrons, etc.),
mitochondria in macros progresses to microcytic
Chronic pancreatitis,
to erythroid precursorsor 9 – 12 g Hb/dL Hypochromic Cells
fish tapeworm
2. DNA synthesis
imparied; Cell
differentiation halted
3. Megaloblastic
precursors
phagocytosed by macrocytic RBCs
macros. Hypersegmented
1.
4. Malabsorption
pancytopenia due to neutrophils &
achlorhydria and lack of eosionphils
intrinsic factor
2. DNA synthesis
imparied; Cell
differentiation halted
3. Megaloblastic
precursors
phagocytosed by macrocytic RBCs
macros. Hypersegmented
4. pancytopenia neutrophils &
eosionphils
1. deficiency: decreased
intake, increased
utilization, or antagonists
(e.g. methotrexate)
2. DNA synthesis
imparied; Cell
differentiation halted
3. Megaloblastic
precursors
phagocytosed by macrocytic RBCs
macros. Hypersegmented
4. pancytopenia neutrophils &
eosionphils

1. causes: Idiopathic,
chemical related,
infections, etc.
2. marrow aplasia
3. pancytopenia
checmical related
anemia may be dose
related, or idiosyncratic hypocellular bone
(chloremphenicol marrow (mostly fat)

1. Malignancy or
myelofibrosis crowds out
bone marrow Dacrocytes,
2. pancytopenia immature RBC's &
3. extramedullary leukocytes among
hematopoesis mature cells

1. Primary: -- EPO;
erythropoietin receptor
hyperfunction
Secondary: ++ EPO;
appropriate (hypoxia) or
inappropriate (normoxia)
2.
Labs Epidemiology Treatment

Osmotic fragility test slenectomy

Avoid oxidative
stressors:
Drugs: antimalarials,
sulfa drugs
More common in the Food: fava beans
Mediterranian & African Others: prolonged
areas since it offers hypoxia, lactic acidosis,
protection from malaria infections
Sickledex (cannot Hydroxyurea therapy
distinguish between trait reduces frequency &
and disease), Affects people of African severity of vaso-
Electrophoresis, decent; protection occlusive crises; survival
DNA testing against malaria is now 50% upto age 50

Worldwide; ++ in Italy &

Greece. More common
in the US. Than a-thal regular blood
elevated HbA2 &HbF (protection against transfusions required in
Dx: electrophoresis malaria) severe form
 50 – 70% immune no compatible blood for
Coomb's test hemolytic anemias transfusion

30% immune hemolytic

anemias
Increased frequency w/
older adults
 Blood type mismatch
more common than
catching blood borne
diseases from
Coomb's test transfusion cease transfusion

++ serum iron
++ serum ferretin
--TIBC
++ serum ferretin
-- serum iron
-- serum ferretin
++ TIBC worldwide: worse in
++ RDW developing countries iron supplements

-- serum iron
++ serum ferretin most common anemia in
-- TIBC hospitalized patients

-- serum cobalamine
++ methylmalonic acid more common in vegans
++ serum homocysteine & breast fed infants of
vegans
Shilling's test & alcoholics? vitamin supplement

-- serum cobalamine
++ methylmalonic acid
++ serum
homocysteineserum Abs
to intrinsic factor or
gastric parietal cells

Shillings test vitamin supplement

 more common in 50 – 200 micro gram
++ serum homocysteine alcoholics daily vitamin supplement

after ACD, most

common cause in
individuals age ≥ 60

associated with cigarette

smoking (appropriate phlebotomy for ≥54
secondary form) hematocrit
Complications/Other
symptoms

splenomegaly
Jaundice
Cholelithiasis (pigment
stones or bilirubinate)
Aplastic crisis w/
parvovirs infections

Rare hepatic/cerebral
vein thrombosis due to
platelet dysfunction
increasees risk of AML

acute hemolysis may

lead to death

++ 2,3 BPG shifts O2

binding curve to the right
Sickle crisis (e.g. bone
pain)
Autosplenectomy (leads
to infections w/ S.
pneumonae & H.
influenzae)
Hemolysis causes
hyperbilirubinemia &
pigment stones

iron overload from blood

transfusions
Bone expansion due to
increased
hematopoesis?
precipitated by cold

hemoglobinunria
frequent
Back pain, burning
sensation, anaphylaxis
neurological deficits:
spinal cord dorsal &
lateral columns
Gastric
(Subacute atrophy
combined
(++ risk of gastric
degenration) w/ spastic
carcinoma)
paraperisis, sensory
Achlorhydria
ataxia, & paresthesia
atrophic gastritis (beefy
tongue)
Neurological deficits –
spinal cord dorsal &
lateral columns:
(Subacute combined
degenration) w/ spastic
paraperisis, sensory
ataxia, & paresthesia
Cortical: dementia
If patient is deficient in
cobalamine, this
supplement Tx might
improve anemia but
worsen neurologic
problems

++ blood viscosity
++ cardiovascular
complications
++ thrombosis &
hemorrhage
Disorder Classification Cause

1st normocytic
normochromic- then
microcytic
Iron Deficiency hypochromic malnutrition

increased utilization
(e.g. during
pregnancy),

acute/chronic blood
loss, or hemodialysis
Ferrochetalase lacks
substrate to complete
heme synthesis

reduced αglobin
synthesis in any of 4
α Thalassemia Microcytic Anemia total genes
gene deletion is most
common cause

Silent carrier: -/a, a/a-

asymptomatic
Mediterranian, Africa
& Southest Asia αThalassemia trait:
(protection against -/-,a/aasymptomatic or
malaria) βthal minor
HbH disease: -/-,-/a-
severe anemia
Hydrops fetalis: -/-,-/-
lethal in utero

inherited defect in 2
β Thalassemia Microcytic Anemia genes
which destroys normal
RNA splice junction-
causing no globin
synthesis
beta globulin is
produced- due to splice
mutation or promoter
region mutation
 children ingest in old
houses because they
Lead Poisoning microcytic anemia used lead paint
genetic, aquired
(myelodysplastic
syndromes), Reversible
(alcohol, lead, vitamin
B6 deficiency, copper
Sideroblastic Anemia microcytic anemia deficiency, isoniazid)
Pathogenesis

1st stage: iron requirement exceeds intake-

progressive depletion of bone marrow iron
stores-

then stores decrease so dietary absorption

increases (hepcidin decreases and stops
interfering) then deficiency impairs iron
synthesis- causing normocytic anemia,
hypochromic microcytic and can cause
dysfunction of ironn containing cellular
enzymes

β chains aggregate into tetramers-Hb H

disease- high affinity for O2 so cause tissue
hypoxia

oxidation and precipitation of intracellular

protein aggregates promote RBC sequestration
by macrophages
HbBart- γchain tetramers bind o2 with
avidity

impaired or no creation of β chains

alpha chains do not form tetramers so they

precipitate within the cell
lead inactivates ALA dehydrase and
ferrochetalase in heme synthesis and produces
microcytic sideroblastic anemia with ringed
sideroblasts in bone marrow, also lead inhibits
rRNA degredation- causing RBCs to retain
aggregates of rRNA (basophilic stippling)

defect in heme synthesis- x linked defect in δala

synthase gene
Signs and Symptoms Diagnosis

CBC- shows anemia

fatigue, SOB, weakness, dizziness, pallor Hgb

Pica, glossitis, cheilosis, concave nails serum iron- low, serum

(koilonychia) severe caused by postcricoid iron binding capacity-
esophageal web- Plummer-Vinson syndrome high
serum ferritin= iron
body stores- low levels
<12ng/mL

bone marrow- absent

iron stores

Evaluation for
severe anemia in HBH hemolytic anemia

splenomegaly d/t increased RBC turnover Peripheral smear

Electrophoresis

DNA testing for

prenatal diagnosis

CBC, smear, serum

LDH, serum
haptoglobin, indirect
Minor- just mild microcytic anemia bilirubin

Intermedia- generally d/t β+/β+ οr β0/β+ may

need transfusions but not severe

Major/Cooley Anemia- β0/β0 microcytic

hypochromic anemia, splenomegaly, bone
deformities, death by age 20
hyperplasia of bone marrow and
extramedullary hematopoiesis in liver and
spleen
produced, but more needs to be produced of
those than a normal HbA1 because they have
a higher O2 affinity and don't unload it very
well
splenomegaly d/t increased RBC turnover

lead lines and

erythrocyte basophilic
lead lines on gingivae (burton lines) and on stippling (retained
metaphyses of long bones on xray, Anemia, aggregates of rRNA in
Abdominal colic, encephalopathy RBCs)
Cell morphology Labs Treatment
bone marrow iron
stores, Hb serum iorn
normal, serum ferritin
falls, increase iron
early- normocytic absorption causes
anemia increase Transferrin oral iron
impaired- transferrin
increased, serum iron
decreased, transferrin
sautration decreases,
late- microcytic serum ferritin receptor
hypochromic level rises
normal appearing
RBCs and indices
develops

Stage 4- microcytosis
and hypochromia
Stage 5- iron deficiency
affects tissues

anisocytosis,
poikilocytosis, target blood transfusions in
cells severe anemia Hb<6 severe
erythroblasts, target
cells, small pale
RBCs, punctuate and RBC elevated but cells
diffuse basophilia microcytic
ringed sideroblasts
with iron laden
mitochondria in bone increased iron and
marrow ferritin, normal TIBC B6- pyridoxine
Complications/Other symptoms

iron overload from transfusions

bone expansion due to increased

hematopoiesis

extramedullary hematopoiesis

iron overload due to anemia and

hypoxia down regulation of
hepcidin
LEAD:
LEAD: Lead Lines on gingivae
(Burton lines) and on
metaphyses of long bones D on x-
ray. Encephalopathy and
Erythrocyte basophilic
stippling.
Abdominal colic and sideroblastic
Anemia. Drops—wrist and foot
drop. Dimercaprol and
EDTA are 1st line of treatment.
Succimer used for chelation for
kids (It “sucks” to
be a kid who eats lead).
Disorder Classification Cause
MEGALOBLASTIC

Vitamin B12 Deficiency

Folate Deficiency

NON-MEGALOBLASTIC
Liver Disease
Alcoholism
Reticulocytosis
Metabolic Disorder- Orotic
Aciduria
Pathogenesis Signs and Symptoms Diagnosis

B12 needed for tetrahydrofolate,

converting homocystein to methionine,
metabolizing methylmaloyl CoA- no B12
gives same symptoms as no folate but
also demyelination is what leads to CNS
effects
Cell morphology Labs Treatment
Complications/Other
symptoms
Disorder Classification
NONHEMOLYTIC ANEMIA

normocytic normochromic or
Anemia of Chronic Disease microcytic hypochromic

Aplastic Anemia normocytic normochromic

Kidney Disease normocytic normochromic
Myelophthtisic Anemia

HEMOLYTIC ANEMIA
INTRINSIC
EXTRAVASCULAR
Hereditary Spherocytosis

Pyruvate Kinase Deficiency

Sickle Cell Anemia
HbC Defect

INTRAVASCULAR

G6PD Deficiency

Paroxysmal Nocturnal destruction of RBCs by

Hemoglobinuria complement system
EXTRINSIC

antibodies directed against

blood causes them to burst-
either warm or cold(cold
Autoimmune Hemolytic aglutinin and paroxysmal
Anemia cold)

IgG (or A) bind to RBCs at

Warm Agglutinin warm temperatures
autoimmune disease high
concentration of IgM directed
Cold Agglutinin at blood cells

Paroxysmal Cold
Hemoglobinuria- PCH/
Donath-Landsteiner presence of hemoglobin in
Syndrome urine after exposure to cold

Microangiopathic Anemia mechanical destruction

Macroangiopathic Anemia mechanical destrucion in

Infectious anemia
Cause

chronic infection, immune activation, and maligancy

o Toxic exposures
• Irradiation
• Drugs or chemicals-
• marrow suppression can be dose related predictable and reversible
(benzene, alkylationg agens, antimetabolites)
• idiosyncratic (chloramphenicol, chlorpromazine, streptomycin)
o viral infections- hepatitis (non-a,b,c or g)
o inherited diseases- fanconi anemia, telomerase defects
o idiopathic- d/t primary defect in stem cells
o suppression of altered stem cells by T-cell immune mechanisms
insufficient erythropoietin

autosomal dominant and recessive inheritance due to mutation in PKLR

gene- less glycolysis means reduction in ATP in red blood cells

x-linked recessive deficiency- mediterranean and african (mediterranean

is worse) antimalarials, sulfonamides, fava beans

defect in PIGA enzyme required to make GPI, located on X chromosome

idiopathic primary, secondary d/t lymphoproliferative disease in adults
or an infection in children (M. pneumo, mono, HIV)

following an infection- when microorganism triggers antibodies

formation that cross react- molecular mimicry

DIC, Thrombotic Thrombocytic Purpura, Hemolytic Uremic Syndrome,

Lupus, Malignant hypertension
Pathogenesis Signs and Symptoms

• elevation of interleukin-6 stimulates hepcidin

release from liver which reduces ferroportin so iron
is not released- instead it is sequestered and not
exported by duodenal epithelim and macrophages
• also inflammatory cytokines increase production
of WBCs which come from the same progenitor as
RBCs so decreased erythropoiesis anemia stupid

o Hypocellular marrow-
hematopoietic cells replaced
by fat
o Infections-
granulocytopenia
o Bleeding-
thrombocytopenia
o Anemia

• Anemia
• Cholecystolithiasis
because RBCs cannot synthesize ATP cellular death • Jaundice
occurs- NAKATPase pump halts so potassium leaks • Splenomegaly
out cell shrinks and diesand is eaten by spleen • Leg ulcers

without the GPI yu have no CD55 that prevents c3- red dicoloration of urine d/t
convertase, and CD59 which blocks c9 from binding hemoglobin and
on cell- at night decreased respiratory rate causes hemosiderin, anemia
acidification of blood and activation of complement symptoms- some have
that RBCs cannot protect themselves against so abdominal pain, difficulty
intravascular hemolysis swallowing, ED, blood clots
IgG or A bind to polysaccharides on RBC in warm
temps, macrophages in spleen pick off pieces of
membrane turning them into spherocytes- not as severe anemia, increased
flexible so they will lyse MCV, hyperbilirubinemia
at low body temp, IgM binds to polysaccharide,
when they return to warmth, complement is
triggered so RBCs lyse

polyclonal IgG anti-P autoantibody binds to RBCs in

cold so red cells are lysed when blood returns to
warmer central circulation- intravascular hemolysis

mechanical destruction in small vessels-

endothelial layer of small vessels are damaged-
fibrin deposition and platlet aggregation so the
blood going thru this gets fragmented and results in
intravascular hemolysis

mechanic destruction in large vessels- heart valves

Diagnosis Cell morphology Labs

• Underlying disorder
• CBC-anemia
• Serum iron- low
• Serum ferritin- high
• TIBC low
• Transferrin receptor-
normal

bone marrow- replaced by fat

and CBC for pancytopenia no cells

CBC, Reticulocyte counts,

Bilirubin
positive indirect coombs test
(direct coombs test looks for
antibodies attached to
surface of RBCs)

schistocytes, helmet cells

schistocytes, helmet cells

 Complications/Other
Treatment symptoms

epo & iron treatments +

underlying disorder

• Equine antithymocyte
globulin, corticosteroids,
cyclosporine
• Hematopoietic cell
transplantation
• Cytokines
• Surgery in thymoma
associated RBC aplasia

not generally necessary-

splenectomy and blood
transfusion if severe
Name

Poiklocytes

Spherocyte

micro-spherocyte

irregularly contracted cell

Elliptocyte

Ovalocyte

Dacrocyte
Target Cell

Stomatocyte

Keratocyte

Schistocyte

Echinocyte (crenated cell)

Acanthocyte

Sickle Cell

Boat-shaped Cell
S-C poikilocyte

Rouleaux

Basophilic stippling

Cabot

pappenheimer bodies

howell-Jolley

Bite Cell

Ringed Sideroblasts
Teardrop cell
Image/ Description
spurr cell
basophilic remnants found in RBC- normally removed by spleen
Disorders Seen

hereditary spherocytosis, autoimmune hemolysis

hereditary elliptocytosis

megaloblastic anemia (also hypersegmented PMNs) marrow failure

HALT said hunter to his target: HbC disease, Asplenia, Liver disease, Thalassemia

helmet cell- DIC, TTP/HUS, traumatic hemolysis

abetalipoproteinemia and liver disease

sickle cell anemia

Anemia of Chronic Disease, alcohol abuse, lead poisoning, Thalassemias

seen in patients with functional hyposplenia or asplenia

G6pD deficiency

sideroblastic anemia. Excess iron in mitochondria = pathologic

Bone marrow infiltration- myelofibrosis, thalassemia
Test Explanation
Anti-parietal cell antibody
Blood smear See-Cell morphology
Bone marrow biopsy

includes all of the following: Red blood cell count,

hemoglobin, hematocrit, RBC indices, MCV, MCH, MCHC,
RDW, WBC and differential, Neutrophils, lymphocytes,
monocytes, eosinophils, basophils, blood smear, platelet
Complete blood count (CBC) count, mean platelet volume (MPV)

RBC count
Hemoglobin (Hgb) total amount of hemoglobin in blood
percentage of blood volume that is made up by RBCs-
Hematocrit (Hct) measured by height in column after centrifugation
RBC indices

differentiating macrocytic, microcytic and normocytic

Mean Corpuscular Volume (MCV) anemia
Mean Corpuscular measure of average amount of hemoglobin w/in an RBC-
Hemoglobin(MCH) indicates hypochromia

Mean Corpuscular Hemoglobin measure of average percentage of hemoglobin in a single

Concnetration (MCHC) RBC- hemoglobin over hematocrit percentage
Red Cell Distribution Width (RDW) indication of anisocytosis- variation in RBC size

indication of ability of bone marrow to respond to anemia-

Reticulocyte Count so if production is adequate
WBC
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Platelet Count

Mean Platelet Volume (MPV) evaluation of thrombocytopenia

2,3 diphosphoglycerate
Erythropoietin

indicator of available iron stores- 1ng/ml of serum ferritin is

equal to 8mg of stored iron- ferritin is also an acute phase
reactant protein (rises 1-2 days after onset of acute illness
and peaks 3-5 days after) most sensitive test for iron
Ferritin deficiency anemia
Folic acid
Heinz body
Hemoglobin electrophoresis
Intrinsic factor
Iron Testing blood test
iron level (Fe)
Total Iron Binding Capacity
Transferrin
Transferrin Saturation
differentiate iron deficiency anemia from anemia of chronic
disease or other low iron anemias- it is a receptor on cells
Transferrin Receptor Assay with high requirement for iron

Sickle Cell Screen

TSH
Total blood volume

Vitamin B12
Zinc protoporphyrin
Direct Coombs Test
Indirect Coombs Test
Donath Landsteiner Test

identify presence of intravascular hemolysis- nonspecific for

Serum haptoglobin
Urinary Hemosiderin
Positive Acid Hemolysis (HAM)
indicating type of hemolytic anemia- haptoglobins bind to
hemoglobin in blood so complex can be metabolized so
more hemolysis causes diminished haptoglobin blood

Serum Bilirubin total bilirubin-direct+indirect

Indirect Bilirubin

Direct Bilirubin
Newborn bilirubin
Urine bilirubin
Erythrocyte Fragility
Normal Results

M-4.7-6.1, F4.2-5.4
m14-18g/dL F:12-16g/dL

M42-52%, F 37-47%, pregnant >33%

80-100fL

27-33pg

33-37%
11.5-14.5%

0.5-1.5% or 2% (higher in infants)

5000-10,000
55-70%, 2500-8000
20-40% 1,000-4,000
, 100-700
1-4%, 50-500
0.5-1.0% 25-100
150,000-400,000

7.4-10.4fL

12-300ng/ml M, 10-150ng/mL F
m80-180mcg/dL, f 60-160mcg/dL
250-460mcg/dL
215-365mg/dL
20-50%m, 15-50%f

M2-5mg/L, W1.9-4.4mg/L

50-220 mg/dL or 0.5-2.2g/L

0.3-1mg/dL
0.2-0.8mg/dL

0.1-0.3mg/dL
1.0-12mg/dL
0-0.02mg/dL
Increased

• Erythrocytosis
• Congenital heart disease
• COPD
• Polycythemia vera
• Severe dehydration
• Hemoglobinopathies
• Thalassemia trait- in response to decreased O2 carrying
capacity of abnormal hemoglobin- more RBCs produced
same as RBC

Same as RBC

• Pernicious Anemia
• Folic Acid deficiency
• Antimetabolite therapy (methotrexate- B12 and folate
inhibitors)
• Alcoholism (malnutrition)
• Chronic Liver Disease

macrocytic anemias

• Spherocytosis: it’s an automated false perception because of

they variation in shape
• Intravascular hemolysis- d/t free hemoglobin in blood so
automated counter sees hemoglobin and incorporates that
into calculations
• Cold agglutinins- false calculation
• Iron deficiency anemia
• B12 or folate deficiency: RBC fragmentation alter size and
shape but also those that were produced before deficiencies
are there
• Hemoglobinopathies
• Hemolytic anemias
• Posthemorrhagic anemias- due to release of premature RBCs
into blood stream (they are larger)

• Hemolytic anemia- marrow attempts to compensate for

shortened RBC survival time by producing large amounts of
RBCs so reticulocytes are released into blood
• Hemorrhage- 3-4 days later
• Hemolytic disease of newborn
• Treatment for iron, b12, or folate deficiency

• valvular heart disease

• immune thrombocytopenia
• massive hemorrhage(release of immature platelets are larger
and increase MPV)
• vitamin b12 or folate deficiency (megaloblastic changes
affect megakaryocyte line so larger platelets are produced that
may have nuclei so MPV increased)
• Myelogenous leukemia (abnormal platelets formed by
neoplastic megakaryocytes)

• Hemochromatosis
• Hemosiderosis (increased iron stores in tissues stimulate
ferritin production for storage)
• Megaloblastic anemia
• Hemolytic anemia (iron is released in bloodstream so ferritin
is stimulated to store excess fee iron)
• Alcoholic/inflammatory hepatocellular disease
• Inflammatory disease
• Advanced cancers (ferritin is an acute-phase reactant protein
increased with acute diseases)
• Chronic illnesses- leukemias, cirrhosis, chronic hepatitis
iron deficiency anemia

increased in iron deficiency

Paroxysmal Cold Hemaglutinin

• biliary obstruction- because after attaching to hemoglobin

haptoglobin is excreted by liver in bile
• infection
• collagen rheumatic diseases
• nephritis
• ulcerative collitis- d/t it being an acute phase reactant
protein

paroxysmal nocturnal hemoglobinuris

Erythroblastosis fetalis, transfusion reaction, sickle cell
anemia, hemolytic jaundice, hemolytic anemia, pernicious
anemia, hepatitis, cirrhosis, sepsis, Neonatal
hyperbilirubinemia, Crigler, Najjar, Gilbert Syndrome
(interruptions in bilirubin conjugation)

gallstones, extrahepatic duct obstruction (if you can't excrete

bilirubin blood levels rise) liver metastasis (intrapeatic or
hepatic duct obstruction) Cholestasis(bile cannot be excreted)

gallstones, obstructions
Decreased

• Anemia
• Hemoglobinopathy/ blood dyscrasias
• Cirrhosis
• Hemolytic anemia- d/t decreased survivial
• Hemorrhage
• Dietary deficiency
• Bonemarrow failure
• Prosthetic valves
• Renal disease
• Pregnancy- d/t overhydration
• Rheumatoid/collagen vascular diseases
• Lymphoma
• Multiple myeloma
• Leukemia
• Hodgkin disease

• Iron deficiency anemia

• Thalassemia α and β
• Anemia of chronic illness

microcytic anemias, hypochromic anemia

• Iron deficiency anemia

• Thalassemia
not clinically applicable

• Pernicious anemia and folic acid deficiency

• Iron deficiency anemia
• Aplastic anemia
• Radiation therapy
• Marrow failure
• Adrenocortical hypofunction
• Anterior pituitary hypofunction
• Chronic diseases

• Aplastic Anemia
• Chemotherapy-induced Myelosuppression:
inadequate bone marrow production releases
small platelets
• Wiskott-Aldrich syndrome
telets) Wiskott-Aldrich syndrome

• Iron deficiency anemia: less iron stores so less

ferritin is required
• Severe protein deficiency
• hemolytic anemias- free hemoglobin after lysis
is bound to haptoglobin and used up but liver
can't replace fast enough before levels drop
• transfusion reactions
• prosthetic heart valves-d/t RBC mechanical
trauma/lysis
• primary liver disease
• hematoma
• tissue hemorrhage

we don't care about decreased- it just means

things are doing fine
Extra Information

MCHC= hemoglobin/hematocrit x100

reticulocyte index should be 1- it is the reticulocyte count x
(patient's hematocrit/ normal hematocrit) a good marrow
response should be 1, if it is below, even with an elevated
reticulocyte level
is =serum iron level/total iron binding capacity x 100
Disorder Classification
Related to Vessels and/or
Primary Platelets
Vessel Wall Abnormalities

Scurvy

Ehler's Danlos vessel disorder

Cushing's Syndrome

Aging Senile purpura

Henoch-Schonlein Purpura leukocytoclastic angiitis

Hereditary Hemorrhagic
Telangiectasia (Osler-Weber-
Rendu Syndrome)

Waldenstrom's lymphoplasmacytic
Macroglobulinemia lymphoma
Amyloidosis

Drug Reactions

Infections
Platelet Disorders
 quantitative platelet
Thrombocytopenia dysfunction

Immunologic Idiopathic
ThrombocytopeniaPurpura platelet destruction

Drug-Induced platelet destruction

Thrombotic
microangiopathies

Thrombotic platelet overactivation and

thrombocytopenic Purpura use

platelet overactivation and

Hemolytic Uremic Syndrome use
Platelet function
abnormalities
Von Willebrand's Disease defect of platlet adhesion

Bernard-Soulier Disease defect of platelet adhesion

Aspirin defect of platlet aggregation

Glanzmann's Thrombasthenia defect of platelet aggregation

Secondary related to Clotting Factors
Hen

Hemophilia A deficiency of clotting factors

Hemophila B deficiency of clotting factors

Vitamin K Deficiency deficiency of clotting factors

related to platelets and
Combined clotting factors
Von Willebrand's Disease
DIC

Liver Disease

Dilutional
Cause

vitamin C deficiency

age related atrophy of vascular supportive tissues

autosomal dominant

somatic mutation in MYD88, somatic mutation in

CXCR4, history of autoimmune disease with
autoantibodies, liver inflammation, HIV, rixkettsiosis

ricketssial and meningococcal diseases

• Decreased production: irradiation, exposure to
drugs/chemicals, Acute leukemia, myelophthisis,
aplastic anemia
• Unreplaced loss of platelets: splenic
sequestration, DIC
• Dilution of platelets: multiple transfusions
• Secondary to AIDs and SLE

• In children- acute reaction to viral infection

• In adults- chronic idiopathic disorder

• Alcohol
• Quinidine
• Heparin
• Sulfa
• Cytotoxic drugs
• Thiazide diuretics

• Deficiency of vWF metalloprotease (ADAMTS13)-

accumulation of high molecular weight multimers of
vWF promote platelet microaggregate formation

post exposure to Shiga toxin or vero toxin by E.coli

0157:H7 or Shigella dysenteriae
vWillebrand's Disease, Bernard Soulier, Aspirin,
Glanzmann's
genetic- most common heritable bleeding disorder

autosomal recessive deficency of platelet GPIb

autosomal recessive deficiency of platelet GPIIb-IIIa

x linked genetic disorder Factor 8 deficiency

x linked genetic disorder Factor 9 deficiency

• Fat malabsorption from pancreatic or small-bowel

disease
• In neonates d/t deficient exogenous vitamin K in
breastmilk and incomplete intestinal colonization
• Release of tissue thromboplastin
• Activation of intrinsic pathway of coagulation
• Secondary activation of fibrinolytic system
• Most commonly in obstetric complications-
toxemia, amniotic fluid emboli, retained dead fetus,
abruption placentae
• Cancer (most commonly lung, pancreas, prostate,
stomach)
• Infection- gnegative sepsis
• Trauma
• Immunologic mechanisms- immune complex
disease, hemolytic transfusion reactions

multiple transfusion of stored blood

Pathogenesis Signs and Symptoms

• extensive primary
hemostatic bleeding- gingival
hemorrhages
• bleeding into muscles and
subQ tissue
• hemorrhagic perifolicular
hyperkeratotic papules-
surrounded with twisted
lack of collagen cross-links corkscrew hair

vascular bleeding, articular

hypermobility, dermal
poor vascular support hyperelasticity, tissue fragility

hemorrhagic areas on back of

hands and forearms

hemorrhagic urticaria
(palpable purpura) fever,
small vessel vasculitis where IgA and C3 are deposited on arthralgias, gastrointestinal
arterioles, capillaries and venules. and renal involvment

malformation of venules and capillaries of mucous and skin

weakness, fatigue, weight

loss, chronic oozing of blood
from nose and gums,
peripheral neuropathy,
cancer of B cels creating a bunch of igM, vascular damage lymphadenopathy- blurring,
from sluding of hyperviscous blood because of all of the IgM loss of vision, headache
vessel damage

immune complex deposition with hypersensitivity vasculitis

involve vascular endothelium leading to necrosis and rupture
of small blood vessels
 • Petechial Cutaneous
Bleeding
• Intracranial bleeding
• Oozing from mucosal
decreased platelets lead to decreased clot formation and surfaces

• Antiplatelet antibodies coat and damage platelets

• Platelets removed selectively by splenic macrophages
• Platelets not removed by spleen can become activated due • Petechia
to antibody attachement and cause aggregation and • Purpura
thrombosis • Mucosal bleeding
• In pregnant women IgG antibodies can cause fetal • Thrombosis- due to
thrombocytopenia, and also the risk of maternal thrombosis antibodies activating platelet
is increased aggregation

• Thrombocytopenia,
• Platelet derived hyaline microaggregates (microvascular • Anemia
platelet thrombi) block and cause damage to RBCs as they • neurologic deficit
pass- thus hemolytic anemia- intravascular • renal dysfunction
• Platelet constant activation leads to thrombocytopenia • fever

• Thrombocytopenia
• Anemia
• Renal insufficiency and
• Platelet derived hyaline microaggregates (microvascular failure
platelet thrombi) block and cause damage to RBCs as they • Prodrome vomiting,
pass- thus hemolytic anemia- intravascular abdominal pain, bloody
• Platelet constant activation leads to thrombocytopenia diarrhea

either defect in platelet adhesion or in platelet aggregation Mucocutaneous bleeding

• Type 1(dominant)- clinically mild, reduced levels of vWF • Mild to moderate
• Type 2 (dominant) –qualitative defects in vWF- they are • Easy bruising
normal in number but unable to for active high-molecular • Mucosal bleeding
weight nultimers- mild to moderate bleeding • Prolonged bleeding time
• Type 3 (recessive)- marked deficiency of vWF and severe • Increased menstrual
phenotype bleeding
vWF is the adhesion molecule of endothelium that GPIb-IXV • Abnormal bleeding after
on platelets binds to so that the shear rates don't pull off the surgical procedures
platelet- when severe factor VIII deficiency NO petechiae and purpura

perioperative/postop
bleeding, bleeding gums,
easy bruising, heavy
menstural bleeding, epistaxis,
without gp1B there is no initial adhesion of platelets on abnormally prolonged
vascular endothelium, so there is bleeding bleeding time
irreversibly acetylates cyclo-oxygenase, preventing platelet
production of thromboxane A2

• Bleeding into tissues

• Hemarthroses
• Muscle hematomas
• Retroperitoneal
hemorrhage
lack of factor 8 cofactor on intrinsic pathway leads to • Excessive bleeding after
bleading from inabiity to activate factor X surgery

• Bleeding into tissues

• Hemarthroses
• Muscle hematomas
• Retroperitoneal
hemorrhage
lack of cofactor 9 leads to inabiility to activate factor 10 with • Excessive bleeding after
factor 8 surgery

Vitamin K is required as a reucing agent to reduce glutamyl • Bleeding

residues on factors (II, VII, IX, X, proteins c &s) to γglutamyl • Easy bruisability
carboxylase residues which allows calcium to bind to the 2 • Mucosal bleeding
negatives and then for the factors to bind to negative surfaces • Hemorrhagic disease of
on platelet lipid membrane. Without vitamin K in its reduced newborn (cutaneous, GI,
form you have no electron donor to form those factors so intrathoracic, intracranial
coagulation cascade cannot occur bleeding)
widespread clotting with consummption of platelets and thrombotic phenomena and
coagulation factors, particularly 2, 5, 8, and fibrinogen hemorrhage
coagulopathy because all factors except vWF produced in
liver
persistent bleeding from
surgical wounds
Diagnosis Labs

raised IgA levels and raised CRP- distinguish

HSP from hypersensitivity vasculittis:
palpable purpura, abdominal angina,
digestive tract hemorrhage, hematuria at
age less than 20
 • Decreased platelet count
• Prolonged bleeding time
• Bone marrow aspiration shows megakaryocytes
decreased when platelet production problem,
increased when caused by increased platlet
destruction

• CBC with platelets

• Normal or increased megakaryocytes
• Exclusion of other thrombocytopenic
disorders (drugs, alcohol,
lymphoproliferative disorders, autoimmune
diseases, viral infections)
• Coagulation studies, LFT, hep C and HIV
tests
• Prolonged bleeding time
• Decreased platelet count
• Normal PT and aPTT and Thrombin
time/fibrinogen
• Megakaryocytes are increased

• Prolonged bleeding time

• Decreased platelet count
• Normal PT and aPTT and Thrombin
time/fibrinogen
• Megakaryocytes are increased

• Blood smear: schistocytes and helmet cells

• Cbc with platelets • Increased megakaryocytes
• Peripheral blood smear • Decreased platelet
• Coombs test • Negative direct coombs test
• LDH • Evidence of intravascular hemolysis (elevate
• PT bilirubin, elevated LDH)
• PTT • Bleeding time prolonged
• Fibrinogen • PT, aPTT, thrombin time/fibrinogen normal
Serum bilirubin

• Blood smear: schistocytes and helmet cells

• Cbc with platelets • Increased megakaryocytes
• Peripheral blood smear • Decreased platelet
• Coombs test • Negative direct coombs test
• LDH • Evidence of intravascular hemolysis (elevate
• PT bilirubin, elevated LDH elevated reticulocytes,
• PTT reduce haptoglobin)
• Fibrinogen • Bleeding time prolonged
Serum bilirubin • PT, aPTT, thrombin time/fibrinogen normal

PT, PTT, bleeding time, platelet count

 • Impaired adhesion prolongs bleeding time
• Deficiency of factor VIII, prolonged aPTT
vWF assay: total plasma vWF, vWF function, • Normal platelet count, PT, Thrombin Time and
plasma factor VIII level Fibrinogen assay

PT, PTT, bleeding time, platelet count all are normal but bleeding time is prolonged

PT, PTT, bleeding time, platelet count normal but bleeding time is prolonged

PT, PTT, bleeding time, platelet count normal but bleeding time is prolonges

• Platelet count • Bleeding time normal

• PT • Platelet count normal
• PTT • PT normal
• Factor VIII and X assays • aPTT prolonged
• vWF activity and antigen and multimer • thrombin time/ fibrinogen assay normal
composition • Factor VIII assay

• Platelet count • Bleeding time normal

• PT • Platelet count normal
• PTT • PT normal
• Factor VIII and X assays • aPTT prolonged
• vWF activity and antigen and multimer • thrombin time/ fibrinogen assay normal
composition • Factor IX assay

prolonged PT and aPTT

microangiopathic hemolytic anemia with
fragmented red cells (schistocytes),
increased fibrin and fibrinogen degredation
products, thrombocytopenia, prolonged
bleeding time, PT, aPTT, and thrombin time
PT, aPTT, thrombin time, bleeding are
prolonged

thrombocytopenia, prolonged PT or aPTT

Treatment Complications/Other

closele related to and may be

a systemic form of IgA
neuropathy- most common
cause of glomerulonephritis
• Oral corticosteroids
• IV immune globulin
• IV anti-D immune globulin
• Splenectomy
• Thrombopoietin receptor
agonist drugs-
• Rituximab
• Other immunosuppressants

• Weakness, confusion or
coma, abdominal pain, n/v,
corticosteroids and plasma diarrhea, arrhythmias by
exchange myocardial damage

hemodialysis and supportive

care
• desmospressin- vasopressin
analog stimulates release of
vWF into plasma and
increases levels of factor VII
• vWF replacement

those treated in early 80s got

HIV from plasma elements

• Normal hemostasis >30% of

normal factor 8 and 9 levels
• Most patients have <5%
levels
• Bleeding severity depends
on bleeding levels

warfarin inhibits vitamin K

epoxide reductase, the
reaction that restores
electrons to vitamin K so it
can be a donor again- for
warfarin overdose give fresh
vitamin K frozen plasma and vitamin K
fix the liver, also give vitamin
K
Test
Activated Clotting Time
Antithrombin III
Bilirubin
Coagulating factor Concentration
CBC
D-Dimer
DIC scfeening
Fibrinogen
Partial Thromboplastin Time (PTT)
Plasminogen
Plasminogen activator inhibitor-1 (PAI-1) antigen
Platelet aggregation
Platelet antibody
Platelelt Count
Platelet function Assay
Protein C, Protein S
Prothrombin Time (PT)
Thromboelastography
Thrombosis indicators
Explanation Normal Results
Increased Decreased Extra Information
Laboratory Screenign Tests in
Selected Hemorrhagic
Disorders
Disorder Bleeding Time Platelet Count

Vascular Bleeding usually prolonged normal

Thrombocytopenia prolonged decreased

Qualitative platelet defects prolonged normal

Hemophilia A Normal normal

Hemophilia B Normal normal

von Willebrand Disease prolonged normal

DIC prolonged decreased

Vitamin K deficiency/
Warfarin Normal normal

Aspirin prolonged normal

Liver failure, early Normal normal

liver failure end stage prolonged decreased

uremia prolonged normal

congenital afibrinogenemia prolonged normal

factor V deficiency Normal normal

factor X deficiency- amyloid
purpura Normal normal

Glanzmann's thrombasthenia prolonged normal

Bernard Soulier Syndrome prolonged normal or decreased

Factor XII deficeincy Normal normal

C1NH Deficiency Normal normal

Anemia Diagnostic Flow

Charts
Hodgkin vs Non
Hodkin Lymphoma Hodgkin Non-Hodgkin

localized, single group of

nodes; extranodal is rare;
contiguous spread (stage is
strongest predictor of Multiple, peripheral nodes;
prognosis) Prognosis is much extranodal involvment
better than with non-Hodgkin common, noncontiguous
Lymphoma spread
majority involve B cells-
characterized by Reed- except those of lymphoblastic
Sternberg cells T cell origin

Binodal distribution- young

adulthood and >55; more
common inmen except for peak incidence for certain
nodular sclerosing type subtypes 20-40 years old
50% cases associated with may be associated with HIV
EBV and immunosuppressions
Constitutional ("B")
signs/symptoms- low grade
fever, night sweats, weight fever constitutional
loss signs/symptoms
tumor giant cell- binucleate
or bilobed with 2 halvs as
mirror images, CD15+ and
Reed Sternberg cell CD30+ Bcell origin

Hepatitis B HBsAg HBeAg

Acute + +
Chronic + +
Resolved - -
Vaccinated - -
PT aPTT

normal normal

normal normal

normal normal

normal prolonged

normal prolonged

normal prolonged

prolonged prolonged

prolonged normal or mildly prolonged

normal normal

prolonged normal

prolonged prolonged

normal normal

prolonged prolonged

prolonged prolonged

prolonged prolonged

normal normal

normal normal

normal prolonged

normal decreased
Anti-HBcAg-IgM Anti-HBcAg IgG
+ -
- +
- +
- -
Confirmatory Tests or Other Significant Findings
megakaryocytes normal or increased when
thrombocytopenia is caused by increased platelet
destruction, decreased when due to decreased
production

platelet aggregation and other specialized studies

Factor VIII assay

Factor IX assay

vWF assay

fibrin and fibrinogen degredation products

low levels of gpIIb/IIIa

low levels of gp1b

hereditary angioedema d/t deficiency of C1inhibitor

gene
Anti-HBsAG
-
-
+
+
Disorder Classification
Lymphoid Neoplasms
Precursor B-Cell Neoplasms

B-Cell Acute Lymphoblastic

Leukemia/Lymphoma (B-ALL) Leukemia
Precursor T-Cell Neoplasms

T-cell acute lymphoblastic

leukemia/lymphoma (T-All Leukemia
Peripheral B-Cell Neoplasms

• Lymphoma-divided into 3 main clinical

variants:
• Endemic(malarial regions, children- because
malaria decreases resistanc)
• Sporadic- non African where malaria is not
holoendemic- EBV associated- less commonly
jaw ileocecal is common
Burkitt Lymphoma • Immunodeficiency associated lymphoma

Diffuse large B-cell lymphoma Lymphoma

Extranodal marginal zone lymphoma Lymphoma- MALToma

Follicular lymphoma Lymphoma- weel differentiated

Hairy Cell leukemia Leukemia-TRAP

Lymphoma- intermediate differentiated

Mantle cell lymphoma lymphocytic lymphoma

Chronic Lymphocytic Leukemia (CLL)/Small Leukemia- well differentiated leymphocytic

Lymphocytic (SLL) lymphoma
Peripheral T-Cell and NK cell Neoplasms

T-Cell chronic lymphocytic leukemia, "knobby"

type T-cell leukemia, T-prolymphocytic
T-Cell prolymphocytic leukemia leukemia/t-cell lymphocytic leukemia

Large granular lymphocytic leukemia Leukemia

Mycosis fungoides/Sezary syndrome cutaneous T-Cell lymphoma

Non Hodgkin Lymphoma- all T-cell lymphomas
that are not contained in the 4: Extranodal,
Cutaneous (mycosis/sezary), anaplastic,
Peripheral T-Cell lymphoma angioimmunoblastic

non-hodgkin lymphoma: 4 clinical entities all

sharing same name- histologically have in
common presense of large pleomorphic cells
Anaplastic large-cell lymphoma that express CD30 and T cell markers
Adult t-cell leukemia/lymphoma T-Cell Leukemia

not in typical lymph node- cutaneous T-cell

extranodal NK/T-cell lymphoma lymphoma, subcutaneous t-cell lymphoma
NK cell leukemia SEE large granuar lymphocytic leukemia

peripheral T cell lymphoma characterized by

systemic disease, polymorphous infiltrate
involving lymph nodes, with prominent
proliferation of high endothelial venules and
Angioimmunoblastic T Cell Lymphoma follicular dendritic cells

Hodgkin Lymphoma Lymphoma

Classical subtypes Lymphoma

Lymphoma- collagen bands that surround at

leaset one nodule and Hodgkin Reed Sternberg
Nodular sclerosis cells with lacunar morphology

Mixed cellularity Lymphoma

Lymphoma- classical HL with scattered Reed-

sternberg cells and nodular or less commonly a
diffuse cellular background of small
lymphocytes- absense of neutrophils and
Lymphocyte rich eosinophils
lymphocyte depletion Lymphoma

Lymphocyte predominance Lymphoma

malignant disease of plasma cells in bone

marrow, second most common hematological
Multiple Myeloma cancer

Plasmacytoma plasma cell neoplasm that forms a discrete mass

small lymphocytic lymphoma with plasmacytic

differentiation: cross between multiple myeloma
Lymphoplasmacytic (Waldenstrom and small lympocytic lymphoma- also called
Macroglobulin) plasmacytoid lymphoma, immunocytoma

plasma cell neoplasm- monoclonal

immunoglobulin in serum or urine without
MGUS (Monoclonal Gammopathy of clinical features of multiple myeloma or
undetermined sign) macroglobulinemia

MYELOID NEOPLASMS
 Leukemia: Subclassification by cytogenic
abnormalities, lineage, or surface markers-
Acute Myeloid Leukemia M3:promyeloblast(MPO+

leukemia: Classified into 3 phases based on

Chronic Myeloid Leukemia clinical characteristics and labaratory findings

Myelodysplastic Syndromes based on number of blasts in marrow

clonal neoplastic proliferations of myeloid stem
Myeloproliferative syndromes cells
Cell Type & Location Epidemiology

Children below 10, down syndrome

B cell precursor arising from bone children older than 5, most
marrow commonly children between 2-5

immature T cell proliferation from Children, lymphoma version is

thymus adolescent males

B cell arising from Germinal Center

B cell lymphoma arising from

marginal zone or Germinal center 70 year old median age

diverse group of B cell neoplasms

from lymph nodes, spleen,
extranodal tissue
B-Cell lymphoma arising from
Germinal Center
B cell leukemia arising from mature
B cells middle aged caucasion men

B cell lymphoma arising from

mantle zone- CD19,20,5+ CD23-

leukemia arising from naïve B cell in 75% of diagnosed patients are over
bone marrow 50

mature- post thymic T cell adults over 30- median 60

adults-rare, only 2-3k% of chronic

Cytotoxic T cells or NK cells lymphoprolif d/o

Helper T-Cell- CD4+ mature adults

10% non-hodgkin lymphomas-

Helper or Cytotoxic T cells mainly older adults

children and young adults-most

commonly men- increased risk with
T-Cell silicone breast implants
Mature CD4+ T-Cells that are Adults • Mainly in Japan, west
infected africa, and Caribbean

Nkcell (most common) cytotoxic T adults- 3% incidence in Asia for

Cell is rare lymphoma

● 15-20% of peripheral T-cell

lymphomas
● 1-2% of non-Hodgkin lymphomas
mature CD$+ follicular T cell- at ● Middle aged and elderly patients
lymph nodes primary site- some ● M:F ratio 1:1
involve sleepn, liver, skin, ● More common in Caucasians than
pleuopulmonary and bone marrow in Africans or Asians

bimodal age group, late 20s and

lymph nodes- single or chain of older than 50- 30% of all
nodes- spread contguously lymphomas, 1% of all cancers

cervical lymph nodes, mediastinum,

bulky disease, spleen or lung (bone,
marrow and liver uncommon but similar males and females, 15-34
5,3,2% respectively) years of age, 70% of all HL

eosiniphils and plasma cells-

eosinophils d/t IL-5 secretion-
Cervical and supraclavicular lymph
nodes, peripheral lymph nodes, males 38 years- more frequent in
spleen, marrow, liver (mediastinum HIV pts and developing countries,
is uncommon) 20-25% of all CHL

peripheral lymph nodes,

mediastinal, bulky disease, lungs,
bones, bone marrow, liver, males 43 yrs- 5% of all classical
waldeyer's ring Hodgkin lymphoma
90% have subdiaphragmatic disease
or organomegaly, predilection for
retroperitoneal lymph nodes,
abdominal organs, bone marrow, males- <1% of all hodgin
marrow involvement is common lymphoma- 30-37yrs
B cell origin- peripheral lymph males, uncommon-5%of Hidgkin
nodes lymphoma

neoplastic proliferation of plasma older individuals (increase risk 1-2%

cells with multifocal skeletal each year) 10-15% of
involvment- hematopoietic neoplasms

3-5% plasma cell neoplasms-

isolated of bone or soft tissue
(oropharynx) of terminally
differentiated B cells- can be either
solitary of bone, extramedullary, or
primary lymph node

● Rare (2% of hematopoietic

neoplasms) malignancy of older
patients (50-69 years) with
involvement of bone marrow,
lymph node, spleen and liver ●
May affect nerve roots, meninges
and rarely brain or small intestine

more common than multiple

myeloma, higher prevalence in
African americans, incidence
Plasma cell increases with age (64 years)
from either a myeloid stem cell or a
myeloblast: 5 classes based on
predominant cell type: Myeloid,
myeloid-monocytic, monocytic, incidence increases with age, 50yr
erythroid, megakaryocytic onset

from either a stem cell or a myeloid

stem cell
Etiology

• chromosomal translocations
t12;21 CBFα and ETV6 in 25%,
9;22(philadelphia as well)

• Chromosomal translocations-
NOTCH1 mutations 50%-70%

8;14 translocation! EBV- C-myc gene

translocation on chromosome 8 and
immunoglobulin heavy chain of
chromosome 14

• EXOC2 gene, PVT1, COA1, HLA-B

mutations
• Immunohistochemical staining
show BCL2, BCL6, MUM1, LMO2,
MYC and p21

lesion begins as reactive polyclonal

reaction to autoimmune disorder or
infectious disease (Sjogren,
Hashimoto thyroiditis, Helicobacter
gastritis)

14;18 translocation (Bcl-2)

translocation fo 11,14- bcl1-cyclin D
and immunoglobulin heavy chains

clonal rearrangements for γ and δ

chains- inversion of chromosome
14, abnormalities of chromosome 8

postulated that T-LGL are

transformed cytotoxic Ts with β
chain rearrangements for T cell
receptor and clonal rearrangement
of γ chain receptor

no known chromosomal
abnormality

no specific chromosomal
abnormality

cytotoxic cell rearrangement of ALK

2p23- 2,5 translocation most
common- an uncommen cancer
HTLV1 provirus is present in cells

EBV associated (B cells EBV+) but T

cells are EBV negative- clonal
rearrangement of T-cell recempot
genes or IgH- chromosomal
abnormalities 3, 5, X

most common subtype (65-70%)

rare form composed of reactive

lymphocytes- associated with EBV
in 40% cases
often HIV associated

cell or origin is less differentiated

thaan plasma cell- express antigens
associated with
myelomonocytes(CD33),
megakaryocytes (GPIIbIIIa)
erythroid cells (glycophorin)

waldenstrom's macroglobulinemia
is a clinical syndrome defined by
serum IgM monoclonal
gammopathy, monoclonal Ig light
chains in urine (bence jones)
hyperviscocity syndrome and B cell
neoplasm involving marrow-
including lymphoplasmacytic
lymphoma

?
t15;17 translocation PML-RARα
inhibits differentiation; 1:12
translocation, 3;21

Philadelphia chromosome 9,22 BCR

fusing with ABL leading to
constitutive activation of tyrosine
kinase IL3betac receptor
Pathogenesis

• constitutive activation of tyrosine kinase receptor causes unchecked proliferation of

lymphoblastic cells (9-22 translocation)
• loss of function mutations in PAX5, E2A or EBF genes
• 12;21 translocations
• loss of function generally leads to unchecked growth or disinhibition of apoptosis

proliferation due to mutation in Notch1 which makes it constitutively active singling the
cell to constantly proliferate

associated with mucosal tissue

disseminated disease in more advanced stage

splenomegaly (red pulp), but no lymphadenopathy

• Small lymphocytic lymphoma- proliferation of small B cells with B markers and 1 T

marker (CD5) like B-chronic lymphocytic leukemia
• B chronic lymphocytic leukemia: 95% of cases, B cell markers CD19, CD20, T cell marker
present CD5. Cells must be CD23 positive but CD10 negative
• T chronic lymphocytic leukemia: 5% of cases, T cell markers, diffuse not nodular lymph
node proliferation, peripheral findings show increased normal lymphocytes, smudge cells
(from fragile neoplastic lymphocytes) Bone marrow with numerous neoplastic
lymphocytes

most common type of mature T-Cell leukemia

CD4+ cells hone to skin producing 3 phases: premycotic(inflammatory), plaque, then

tumor phase

helper or cytotoxic t cells efface the lymph nodes by over proliferation and activation of
eosinophils

constitutively active tyrosine kinases trigger signaling pathways that cause unchecked
proliferation- unchecked proliferation leads to increasing damage in the DNA which
causes other mutations and then cancer
HTLV1 provirus infects and causes circulating lymphocyte proliferation with an irregular
nuclear contour, leading to visceral involvement, hypercalcemia and lytic bone lesions
(because of RANKL induction)
destructive extranodal masses- sinonasal most common (destructive nasopharyngeal)
Testis and skin are less common- tumor invades small vessels causing extensive ischemic
necrosis

expansion of EBV+ B cells due to immunodeficiency

lymph node has broad collagen bands, Reed sternberg cell variant present in nodular
sclerosis is called Lacunar cell- clear space surrounding malignant tumor cell
few lymphocytes, many reed-sternberg cells

lympho-histocytic variants- L&H cells- popcorn cells that are negative for CD15 and CD30

a whole bunch of light chains are produced and (IgG and IgA) and these plasma cells
produce and secrete IL3 (inhibit osteoblast progenitor), secrete DKK1 (inhibit OPG
osteoblast), stimulate MIP1αand RankL to stimulate osteoclast (osteoclast stimulates
everything with IL6) so increase calcium in blood leads to neuronal tetany, and light
chains get filtered thru glomerulus in kidneys- lead to renal failure in 20-30%- when the
light chains urinated they are called Bence Jones proteins. Anemia (shift myeloid to
lymphoid progenitor cell, over produciton of plasma cells in marrow, failing kidney)

Extramedullary plasmacytoma:
● Arises outside bone marrow; often in nasal cavity, nasopharynx, sinuses, oropharynx,
lung or any other body site
● May recur locally, but only infrequently progresses to myeloma, less often than solitary
plasmacytomas of bone
● Morphologic features similar to solitary plasmacytoma of bone

has an M spike, neoplastic cells infiltrate many organs (lymp nodes, spleen, bone
marrow) no lytic bone lesions, serum calcium does not increase

paraprotein discovered unexpectedly- 70% IgG, 15% IgM, 12%IgA, 3%

myeloblast, normal precursor of white blood cells, accumulates genetic changes that
freeze the cell in immature state and prevent differentiation. Other mutations disrupt
genes controlled by differentiation leading to uncontrolled growth of immature clone
cells

constitutive activation speeds up cell division and inhibits dna repair causing genomic
instability and makes cell more susceptible to further abnormalities

dysplastic changes: Pelger Huet cells (aviator glasses nuclei) ring sideroblasts, nuclear
budding, "pawn ball" megakaryocytes

bone marrow is markedly hypercellular, all cell lines ar eincreased in number

Signs and Symptoms

• Abrupt, stormy onset- days to weeks

• Depressed marrow function symptoms: fatigue, fever, bleeding
• Bone pain and tenderness d/t marrow expansion
• Generalized lymphadenopathy, splenomegaly, hepatomegaly
• CNS manifestations d/t meningeal spred

General acute leukemia symptoms + mediastinal mass- may

compress SVC

african type involves mandible or maxilla associated with EBV,

american type nonendemic sporadic involves abdomen (bowel,
retroperitoneum, ovaries) high incidence in AIDS

high grade lage cell B-lymphoma with diffuse growth pattern,

aggressive rapidly proliferating tumor
dry tap bone marrow aspiration, enlarged spleen

• Stage 0: absolute lymphocytosis (>15,000) without adenopathy,

hepatosplenomegaly, anemia, thrombocytopenia
• Stage 1: absolute lymphocytosis with lymphadenopathy without
hepatosplenomegaly, anemia, or thrombocytopenia
• Stage 2: absolute lymphocytosis with either hepatomegaly or
splenomegaly with or without lymphadenopathy
• Stage 3: absolute lymphocytosis and anemia (hgb<11) with or
without lymphadenopathy, hepatomegaly, or splenomegaly
• Stage 4: absolute lymphocytosis and thrombocytopenia
(<100,000) with or without lymphadenopathy, hepatomegaly,
splenomegaly, or anemia

hepatosplenomegaly, generalized lymphadenopathy, skin infiltrates

cells can be found in peripheral blood, nodes, marrow, spleen, liver,
skin- high lymphocyte count with anemia and thrombocytopenia
are common, indolent leukemia, hypogammaglobulinemia

Indolent course initialy mild to moderate lymphocytosis and

splenomegaly, neutropenia occurs even tho there is no marrow
infiltration

sezary variant because it is disseminated where skin manifests as

generalized exfoliative erythroderma, mycosis has cutaneous
patches, plaques, nodules, generalized erythema, indolent

generalized lymphadenopathy with eosinophilia, pruritis, wieight

loss

lymph node systemic involvement in 2, and cutaneous soft tissue

disease in the other
• Adults with cutaneous lesions RASH
• Marrow involvement
• Hepatosplenomegaly
• Generalized lymphadenopathy
• Peripheral blood lymphocytosis
• Hypercalcemia- lytic bone lesions
• Aggressive

usually presents with advanced stage disease- hepatosplenomegaly,

polyclonal hypergammaglobulinemia, fever, weight loss, skin rash
(pruritis), pleural effusion, arthritis, ascitis

painless enlargement of lymph nodes- B-cell symptoms (Pel Ebstein

fever that comes and goes) weight loss, night sweats

most present with stage II, or 1, B symptoms in 40%

B symptoms are frequent, more often stage III or IV

B symptoms are rare, Stage 1 or 2 presentation

more advanced stage and with B symptoms at presentation, more
aggressive than other subtypes, may be part of continuum with
mixed cellularity subtype
indolent- nodular behavior in young ment with cervical or axillary
adenopathy, stage 1 or 2 presentation

anemia, infections, renal failure, proteinuria, fractures, dehydration,

lytic bone lesions(HRAL)

Primary lymph node plasmacytoma:

● Rare, must exclude metastatic multiple myeloma (40% of high
stage myelomas metastasize to lymph nodes), metastatic upper
respiratory tract plasmacytomas (15% metastasize to cervical lymph
nodes) and Castleman’s disease
● Often involves cervical nodes, mean 5 cm, 40% had serum
monoclonal proteins, most patients had localized disease and were
cured after local excision or radiation, similar to other
extramedullary plasmacytomas

hyperviscosity syndrome (because IgM is BIG) visual abnormalities

d/t vascular dilations and hemorrhages in retina, Neurologic
headaches and confusion, bleeding and cryoglobulinemia which
precipitate at low temps and may cause raynaud phenomenon and
cold urticaria

Paraprotein is usually discovered unexpectedly: 70% IgG, 15% IgM,

12% IgA, 3% biclonal; monoclonal light chain in urine in 1/3
● Serum immunoglobulin level less than 3g/dl
● No myeloma-related organ or tissue impairement (no CRAB
features related to myeloma: hypercalcemia, renal insufficiency,
anemia, bone lesions)
related to replacement of normal bone marrow by leukemic cells-
anemia, thrombocytopenia, neutropenia, symptoms happen early

• chronic phase: asymptomatic or mild symptoms of fatigue, left

side pain, joint or hip pain, abdominal fullness
• accelerated phase- 10-19% myeloblasts in blood or bone marrow,
>20% basophils in blood/marrow, platelet count <100,000 or more
than 1 mil, cytogenic evolution with new abnormalities in addition
to Philadelphia chromosome, increasing splenomegaly
• Blast crisis: >20% myeloblasts or lymphoblasts in blood or bone
marrow, Large clusters of blasts in bone marrow on biopsy,
chloroma development
Diagnosis
acute lymphoblast are all TdT positive

• CBC and peripheral blood smear show blast cells

• Bone Marrow Exam shows blast cells between 25-95%, Basophilic
cytoplasm and larger nuclei, Nuclear chromatin is delicate and stippled,
Nucleoli absent or inconspicuous, Interspersed starry sky macrophages
• Histochemical studies
• differentiated from T cell by markers (over 10) CD10, 19,20
• myeloperoxidase negative PAS positive, TdT positive

• CBC and peripheral blood smear show blast cells

• Bone Marrow Exam shows blast cells between 25-95%, Basophilic
cytoplasm and larger nuclei, Nuclear chromatin is delicate and stippled,
Nucleoli absent or inconspicuous, Interspersed starry sky macrophages
• Histochemical studies
• differentiated from B cell by CD markers (generally T cell are below 10)
• myeloperoxidase negative PAS positive, TdT positive

biopsy of lymph node, staging includes CT of chest, abdomen and pelvis,

bone marrow biopsy, CSF cytology and PET-
lymphocytes have hairlike cytoplasmic projections, TRAP stain diagnostic

first suspected with lymphocytosis, then demonstrated wth abnormal B

lymphocytes in blood- cluster differentiation 5 and cd23 present

HTLV-1 negative, serum gamma globs normal, no paraporteins present

immunohistochemistry of cells reveals CD3+ T cell vriants or CD3-,CD56+

for NK cell variants

sezary cells on blood smear have cerebriform like nuclei, express

adhesion molecule CLA and chemokin CCR4 and CCR10 which hone to
skin, PAS positive T-lymphocytes are present in epidermis

immunophenotyping: mature T-Cell phenotype: CD2,3,5, αβ or γδ,

receptors, helper or cytotoxic origin (CD 4 or 8)

examination of enlarged lymph node- hallmark cells and CD30+-

recognition of large cells with pleomorphic kidney shaped nuclei,
paranuclear eosinophilic region(doughnut cells) and abundant cytoplasm
(may express CD3 or CD4) only 1 systemic type expesses ALK
HTLV1 antibody is detected in serum, Cells with mutlilobed nuclei (clover
leaf or flower cells)- lytic bone lesions

large azurophilic granules are seen in tumor cells that resemble NK cells,
they have killer Iglike receptors, express CD3 and NK cell markers

Cytology● Small to large cells with moderate to faint basophilic

cytoplasm without azurophilic granules and sometimes with
microvacuoles, often irregular or indented nuclei, moderately condensed
chromatin
monoclonal plasma cells in bone marrow, >10%, presence of monoclonal
antibodies in serum or urine, presence of one or more of following
(hypercalcemia, renal insufficiency, anemia, lytic bone lesions)

differential: myeloma cells are mor anaplastic, plasmacytosis no light

chain restriction of plasma cells

● IgM monoclonal gammopathy of any concentration

● Bone marrow infiltration by small lymphocytes showing plasmacytoid
or plasma cell differentiation
● Intertrabecular pattern of bone marrow infiltration
● Immunophenotype is surface IgM+, CD19+, CD20+, CD22+, CD25+,
CD27+, FMC7+, CD5 variable, CD10-, CD23-, CD103-, CD108-

● <10% clonal plasma cells in bone marrow

● Plasma cells lack nucleoli
crystal aggregates of MPO(auer rods), punched out nucleus with an aur
rodd Blasts in blood- low cytoplas,

CBC shows increased granulocytes, basophils and eosinophils increased

(differentiate from leukemoid reaction), Bone marrow biopsy,
cytogenetics detechs philadelphia chromosom
Labs Treatment

Anemia, Neutropenia, Thrombocytopenia,

Immunohistochemistry:preB cells are arrested
at stages preceding surface immunoglobulin excellent response to
expression so they express CD19, PAX5, and chemotherapy- prophylaxis to
CD10, Ce20 scrotum and CSF needed

Anemia, Neutropenia, Thrombocytopenia,

ImmunohistochemistrypreT cells arrested at
early intrathymic stages so often express
CD1,2,5&7 (CD2-8 NOT 10)

starry sky benign macrophages-because they

have engulfed macrophages of malignant
lymphocytes chemotherapy with rituximab

doesn't respond
 excellent response 2CDA which
inhibits adenosine deaminase and
increased levels of toxic
deoxyadenosine (adenosine
accumulates to toxic levels in
neoplastic B cells(part of purine
degredation pathway))

CBC, peripheral smear, treatment not needed in early

immunohistochemistry stage, very indolent cancer

medium sized lymphocytes with single

nucleoli and basophilic cytoplasm with
occasional blebs or projections- irregular
nuclear shape - smudge cells d/t delicate difficult to treat, alemtuzumab
lymphocytes helps but survival is still low

Lymphocytosis, sites of involvment in

peripheral blood, bone marrow, spleen, liver

aggregates are Pautrier microabscesses

pleomorphic mixture of variably sized

malignant T cells in lymph nodes

blood smear morphologic variants: small cell

(cells with same immunophenotype), CHOP, radiationchemotherapy- but
sarcomatoid, signet ring good prognosis
hypercalcemia

circulating immune complexes, cold

agglutinins with hemolytic anemia, positive rh moderately aggressive- may
factor, anti-smooth muscle antibodies- respond to steroids

chemo and external beam

radiotherapy survivors have
increased risk for 2ndary
nonhodgkin lymphoma or acute
leukemia
Blood & Urine: (anemia, abnormal RBC,
increased paraprotein, decreased normal
antibodies, hypercalcemia, increased blood
urea/nitrogen, increased creatinine, urinary
bence jones) BONES: bone aspiration, bone poor prognosis if no treatment, 3
marrow biopsy >10% plasma cells, xray- years with chemotherapy- poorer
osteoporosis, CT scan for lesions prognosis with cyclin D1+

with local radiatin

smear: russel bodies (cytoplasmic

immunoglobulin) & Dutcher bodies
(intranuclear immunoglobulin) may be
present● Moderate to severe normochromic
anemia with marked rouleaux formation (like
partially stacked coins)
● 30% have leukemia composed of no cure- plasmapheresis for
lymphocytes and lymphoplasmacytoid cells hyperviscosity and hemolysis

● Follow with serial measurements

of monoclonal protein but usually
no specific treatment
 Chemotherapy (induction and
consolidation), stem cell
transplantation- altransretinoic acid
immunohistochemistry, CBC, peripheral blood in promyelocytic subtype with
smear (blasts with auer rods) 15;17translocation

targeted therapy by imatinib

mesylate at BCR-ABL
Complications/Other

classic: 12;21 has a good prognosis- seen in kids, t9;22 has poor prognosis seen in adults
(philadelphia chromosomes Ph+ALL)

usually called acute lymphoblastic lymphoma

most common type of non-hodgkin lymphoma, subtypes immunodeficiency associated B-

cell lymphoma(EBV), body cavity large B cell lymphoma(HHV8)
Richter's syndrome (transformation of CLL to fast growing diffuse large B cell lymphoma),
hypogammaglobulinemia(infection), warm autoimmune hemolytic anemia,
transformation to high grade lymphoma

positive for pan-t antigens- CD2,3,7, negative for TdT and CD1a, CD4+/CD8- in 60%,
CD4+CD8+ 25%, CD4-/CD8+ in 15%

indolent tumors with long survival rate

worse prognosis than mature comparable B cell neoplasms

poor prognosis, rapidly progressive disease which is fatal in months to a year even with
chemotherapy

poor prognosis in advanced disease because they do not respond to chemotherapy, but
the do respond to radiation

may progress to diffuse large B-Cell lymphom (common), classical hodgkin lymphoma,
plasmacytoma, small b-cell lymphoma, peripheral t-cell lymphoma- mean survival <3
years- death d/t infection

worse prognosis depends on more reed-sternberg cells being present

great survival- >90% for 5 years

worse prognosis than nodular sclerosis but better than lymphocyte depleted
● Asymptomatic (smoldering) myeloma: patients with no related organ or tissue
impairement; 10% per year progress to symptomatic myeloma for the first 5 years, only
3% per year for the next 5 years and 1% per year for the subsequent 10 years
● Non-secretory myeloma: 3% of plasma cell myelomas show absence of M-protein by
electrophoresis or immunofixation; clinical features similar to secretory myeloma except
for low incidence of renal insufficiency and hypercalcemia
● Plasma cell leukemia: clonal plasma cells > 20% of the leucocyte differential count;
aggressive disease

may have poorer prognosis than other small B cell lymphomas if advanced age, peripheral
blood cytopenias high beta2 microglobulin levels

Risk of progression to overt myeloma is 1% per year; can evolve to myeloma, amyloidosis,
Waldenstrom’s macroglobulinemia or other lymphoproliferative disorder
AML Subtype: Acute Promyelocytic Leukemia t(15;17) disrupts retinoic acid receptor so
can't mature- promyelocytes, lots of auer rods which increases coagulation risk so DIC-
treat with alltrans retinoic acid (ATRA) which causes them to go to neutrophils

prognosis really good after imatinib

are considred preleukemias because pt have an increased risk of developing acute

leukemia
Microscopy
● Bone Marrow: focal or diffuse involvement by small B cells with
plasmacytic differentiation and cytoplasmic (Russell) and nuclear
(Dutcher) PAS positive inclusions
● Inclusions are cytoplasmic immunoglobulin and are nonspecific
● Diffuse involvement is associated with decrease in normal
hematopoietic cells
● Often has reactive mast cells, epithelioid histiocytes, mature plasma
cells
• monoblast AML- acute monocytic leukemia- myeloblasts build up
without myeloperoxidase, infiltrates gums
• megakaryoblastic leukemai- often no myeloperoxidase, associated
with down syndrom before age of 5,
• conditions that lead to AML- myelodysplastic syndrome- blast build
up in bone marrow
• myelodysplasia can also lead to AML because of low blood blood cell
count if the blast builds up to over 20%
• tissue form is called granulocytic sarcoma (chloroma)
• M0 undiferentiated myelogenous leukemia
• M1 myeloblastic leukemia without maturation
• M2 myeloblastic leukemia with maturation (some promyelocytes
• M3- hypergranular (microgranular) promyelocytic leukemia- Auer rods present, DIC d/t release
of thromboplastic substances in granules (especially when treatment kills tumor cells) 15;17
translocaation (PML and RARα)
• M4- myelomonocytic leukemia with both myeloblasts and monoblasts
• M5 monocytic leukemia (gingival infiltrates)
• M6 erythroleukemia (Di Guglielmo disease) abnormal erythroid precursor that show binucleate
and megaloblastic changes
• M7 acute megakaryocytic leukemia- associated with acute myelofibrosis d/t release of platelet
derived growth factor
 Acute
ia
em
uk
Le

Chronic

Hodgkins
as
om
ph
m
Ly

B-Cell

Non-
Hodgkin's T-Cell

Plasma Cell Neoplasms

Malignant
Benign
Syndromes

Leukemia= neoplasms with

widespread involvment of
bone marrow
masses arising from lymph
nodes- presentations often
blur definitions
acute lymphoblastic leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Chronic lymphoblastic Leukemia (CLL/SLL)
Chronic Myelogenous Leukemia (CML)
Hairy Cell Leukemia
Lymphocyte Predominant (LP) type
Lymphocyte Depleted (LD) Type)
Lymphocyte Rich (LR) type
Mixxed Cellularity type
Nodular Sclerosis
Small Lymphocytic Lymphoma (CLL/SLL)
Follicular Lymphoma
Diffuse Large B-Cell Lymphoma
Burkitt's Lymphoma
Lymphoma)
MALToma (marginal zone lymphoma)
Lymphoplasmacytic lymphoma (Waldenstrom)

Lymphoblastic Lymphoma
Peripheral T-Cell Lymphoma
Micosis Fungoides (MF)& Sezary Syndrome (SS)
Adult T-Cell Leukeumia-Lymphoma
Anaplastic Large Cell Lymphoma
Multiple Myeloma
Plasmacytoma
Lymphoplasmacytic (Waldenstrom Macroglobulin)
MGUS (Monoclonal Gammopathy of undetermined sign)
Chronic Myelogenous Leukemia (CML)
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
Pathophysiology Etiology & Age Group

type

chronic lymphocytic leukemia

T-ALL proliferation and non

differentiation of immature T-Cell- goes
to thymus, forms lymphoma teenage boys
Clinical Manifestations Diagnosis Treatment
Disorder
Leukopenia

Leukopenia

Neutropenia
Eosinopenia
Lymphocytopenia
Leukocytosis
eosinphilia

neutrophilia
Lymphocytosis
basophilia

Lymphadenitis

Acute Nonspecific Lymphadenitis

Chronic Nonspecific Lymphadenitis
Classification

Neutropenia, Agranulocytosis

suppurative lymphadenitis
Typical Patient
Cause
o BSC suppression- aplastic anemia
o Infiltrative marrow disorders
o Suppression ofo commited precursors
o Disease states by ineffective granulopoiesis
o Inherited conditions (Kostmann syndrome,
ipairing differentiation)
• Accelerated removal or destruction of
neutrophils
o Neutrophil injury by immunologic
disorders (SLE) or drug exposures
o Splenic sequestration
o Increased peripheral utilization in
overwhelming infections

aplastic anemia, immune destruction (SLE) septic shock

infection (acute appendicitis), sterile inflammation with

necrosis (acute MI) drugs (corticosteroids)

most commonly S. aureus infection, cat scratch disease, IV

drug use, mesetneric lymphadenitis, lymphogranuloma
venereum, Staphylococcal infection- Necrosis: anthrax,
bubonic plague, kikuchi disease, meliodosis, tularemia,,
typhoid fever
Pathogenesis

decreased production, increased destruction

(complement/macrophages), activation of neutrophil
adhesion molecules (increase number of neutrophils adhering
to endothelium by endotoxins)

increased bone marrow production of neutrophils or

decreased activatio of adhesion molecules d/t corticosteroids,
catecholamines, lithium

regional lymph nodes infected by draining from pyogenic site-

superficial nodes most common- early phase dilated sinus
contain proteinaceous fluid with granulocytes and
macrophages that infiltate parenchyma and create
microabscesses- bacteria may be present- LATE phase
lymphocytes plasma cells macrophages and debris are inside
lymph node
Signs and Symptoms

• Interrcurrent infections
• Malaise
• Chills
• Fever
• Marked weakness and fatigability
• Ulecerating necrotizing lesions of gingiva,
buccal mucosa, pharynx
• Opportunistic infections
• Infections fulminant
• Broad spectrum antibiotics at first sign

infection! Fever
Diagnosis

WBC<1500
Labs
Treatment
Complications/Other