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Hematology

DISORDERS

ETIOLOGY
Hgb/Hct
Sign of underlying disease
Hgb/Hct females<males
Lower in pregnancy

Anemia

Production
Problem
Destruction
Problem

Either hemolysis or
bleeding

CC/HPI/PE
PMH: autoimmunity,
malignancy, renal/liver
disease, CAD, HTN, DM, GI
Ethnic Origin: AA,
Mediterranean
Diet: veg/vegan, alcohol,
pica
GI surgery
Drugs
Bleeding
Exposures: lead, benzene
PE: Skin: jaundice, nail
changes, pallor, petechia,
palmar creases, ulcers
Musculoskeletal: lead
lines, bone pain,
pathologic fx
CV: hypotension,
tachycardia
Other: lymphadenopathy,
splenohepatomegaly,
neurologic/neuropathy,
glossitis, gum changes,
Hemoccult+ stool

DX
Functional: production
(90%) or destruction
(10%) problem
Look at reticulocyte count
Normal response to
anemia increased
retics/RBC production

LABS/TESTS
Retic <2% = production
problem: bone marrow
not responding to anemia
(marrow damage, iron
deficiency, decreased
stimulation)
Retic >2% = destruction
problem: bone marrow
fails to compensate for
loss of RBC (acute blood
loss, membrane
abnormality,
autoimmunity, hemolysis,
hemoglobinopathy)

Look at MCV
Macrocytic >100
Normocytic: 80-100
Microcytic <80

Retic <2%
Microcytic = area of
central pallor is smaller
Macrocytic = area of
central pallor is beefy
(compare sizes to nucleus
of leukocyte)

TX

OTHER

Hemolysis:
Extrinsic C+ or CC+ drug, warm Ab or
cold Ab
Intrinsic Hgb,
Membrane, Enzyme

Not compiled by Drew Murphy

Hematology
Microcytic
Anemia

Thalassemia

TICLS
Thalassemia
Iron Deficiency
Chronic Inflammation
(30%)
Lead poisoning
Sideroblastic

Hereditary
Reduced/absent
production of globin
chains ( or )
-intrinsic hemolytic
anemia
Gene deletion Hbg
chain synthesis
Severity depends on how
many of the 4 -Hbg
genes are deleted

HbA = 2 and 2 = 98% in


adults
HgA2 = 2 and 2 (1-2%)
HgF = 2 and 2 (Hgb of
fetal life, at age 1, less
than 1% in adult Hgb)
Seen in Asian,
Mediterranean and less
commonly in African
decent

Alpha
Thalassemia

Hemoglobin
H Disease

Hg is unstable chronic
hemolytic anemia

Varying severity
Pallor, splenomegaly

- transfusion support
- splenectomy
- Hematopoietic stem cell
transplant
- iron chelation

4 -Hbg genes present:


normal, no anemia,
normal MCV
3 -Hbg genes present:
silent carrier, no anemia,
normal MCV
2 -Hbg genes present:
alpha thal train, milkd
microcytic anemia
1 -Hbg gene present:
Hgb H disease, very
microcytic, hemolysis,
variable anemia
0 -Hbg genes present:
hydrops fetalis,
incompatible with life
-Microcytic (MCV = 60-70)
-Peripheral
smear=abnormal
-Retic count >2% due to
chronic hemolysis
-Hgb electrophoresis: HbH
(10-40%)

-splenectomy may be
helpful
- folic acid
- avoid medicinal iron and
oxidative drugs (sulfa

Not compiled by Drew Murphy

Hematology
Alpha-Thal
Trait
Beta
Thalassemia
Homozygous B0
= Thalassemia
major or
Cooleys anemia

Mild anemia

Nearly normal
erythropoiesis
Normal life expectancy
Normal clinically

Caused by gene mutations


not deletions
B0 = absent chain
B+= reduced chain

Ethnicity: Mediterranean
(Italian, Greek), less often
Asian or African origin
-varying degree of anemia

Beta chains are absent


-severe chronic hemolysis
and anemia

Bony abnormalities on PE:


due to expansion of bone
marrow = chipmunk
faces
-growth retardation
-jaundice
-hepatosplenomegaly
- some bony
abnormalities

Homozygous B+ =
Thalassemia
intermedia

Beta chains are reduced


-moderate chronic
hemolysis and anemia

Heterozygous B0 or
B+ = Thalassemia
minor

-mild anemia

-no PE abnormalities
-no bony abnormalities

-most common cause of


anemia worldwide
Causes:
Decreased intake: poor
diet (milk babies)
Decreased absorption:
gastric resection, celiac
Increased loss: gastritic, GI
bleed, hemodialysis,
menorrhagia, blood
donation, GU, neoplasm
Increased requirements:
pregnancy, lactation,
infancy, adolescence

-fatigue, dyspnea on
exertion, tachycardia
-cheilosis, nail changes
-dysphagia (plummerVinson syndrome)
-pica: ice, starch, clay/dirt
- Iron deficiency =
symptom not a disease

Iron
Deficiency
Anemia

Dx of exclusion
Genetic testing available

Dx shortly after birth


when HgF normally
decreases more
obvious disease

Extremely low Ferritin Lvs


- Iron deficiency anemia in
an adult = most likely due
to blood loss
- GI bleed until proven
otherwise!!
-In children = nutritional
deficiency

-Hemoglobin
electrophoresis: no in
HbA2 or F, no HbH
Microcytic (MCV = 70-80)
-Increased % of Hb A2 & F
compared to A
- & sub for chains
-excess a-chains are
unstable damage to
RBC membrane
hemolysis in periphery
and bone marrow
-iron overload
-predominantly HgF
-little to no HbA

-no treatment required


-genetic counseling
offered

-microcytic

-transfusion dependent
- folate
- splenectomy
- iron chelation
- allogeneic bone marrow
transplant for cure

-iron overload
-Hgb = 10% HbA2 and the
rest is HbF

-occasional transfusions in
periods of stress

-Hgb = mostly HbA and 48% HbA2


-sometimes 1-5% HgF

-rare transfusions
- no treatment required
- genetic counseling
offered
-identify specific cause &
target treatment
- multiple formulations
- oral iron w/stool
softener: Ferrous Sulfate
325mg TID
- multivitamins
- Eldertonic (MVI + sherry)
- some oral contraceptives
- parenteral if oral is not
tolerated: anaphylaxis risk
lower w/newer drugs
- IM of iron dextran: use
Z-track technique

-initially =
normocytic/normochromi
c
microcytic/hypochromic
as iron stores deplete
-Hgb will before MCV
-serum iron = very low
-TIBC = high
- RDW = high
-% salt = low
- ferritin = low
-absent marrow iron = 0

Easy to confuse with iron


deficiency

Dont confuse w/iron


deficiency: iron studies
will be normal
Iron absorption: diet,
caloric intake, absorptive
capacity of stomach/sm
intestine
-heme iron (meat source)
- nonheme form (veggies)

Not compiled by Drew Murphy

Hematology
Include serum iron, TIBC,
RDW, serum ferritin

Ferritin lvs reflect rion


stores
TIBC = total iron binding
capacity: reflects
availability of iron binding
sites on transferrin mols

Iron Study
Iron Store
Depletion

Stage 1 of Iron Deficiency

normal morphology

Iron-Deficient
Erythropoiesis

Stage 2 of Iron Deficiency

No morphologic changes

IronDeficiency
Anemia

Stage 3 of Iron Deficiency

Anemia of
Chronic
Disease

Common Causes: liver


disease, acute or chronic
infection (HIV), chronic
inflammation (RA, lupus),
hypothyroidism, renal
disease
(diabetic/hypertensive),
malignancy
-often due to
erythropoietin stimulation
of bone marrow
- RBCs shortened life span
and EPO response is
inadequate to maintain
Hgb

-mild to moderate anemia


-renal disease more
severe anemia

- consider iron or folate


def if anemia is severe
-Signs & Sx related to
underlying disease
process
-Dx of exclusion

-ferritin <20
-iron indices normal
-no anemia
-ferritin<15
- iron indices change
- absent marrow iron
-mild normocytic anemia
-abnormal iron indices
-serum iron = low
-TIBC = high
-% salt = low
- ferritin = low
-absent marrow iron = 0
-microcytic changes
- abnormal peripheral
blood smear
(anisocytosis)
- platelets may
-Microcytic or normocytic
- 1/3 progress to mild
microcytic/hypochromic
anemia due to defect in
moving iron into RBCs
- normal appearing
peripheral smear
- retic = normal
- serum iron and TIBC =
low
- ferritin = high
- RDW = normal
- marrow iron stores =
norm
- erythropoietin - low

-evaluate & treat blood loss


- oral iron supplementation:
ferrous sulfate po tid
- encourage stool softeners
-parenteral iron: more risky
- check CBC in 3-4 weeks: Hgb
normalizes quickly
- check ferritin in 8 weeks:
once normal stop
treatment

For acute anemia, serum


iron is more dependable
-For chronic illness use
ferritin

-no treatment is generally


needed unless pt is
symptomatic or
transfusion dependent
- treat co-existing
deficiencies (iron, folate)
- treat underlying
disease/infection
- erythropoietin injections
(Procrit, Aranesp) usually
w/iron
- transfusions w/chelator

Not compiled by Drew Murphy

Hematology
Sideroblastic
Anemia

Vitamin
B12
Deficiency

Pernicious
Anemia
Folic Acid
Deficiency

-enzyme disorder: body


has enough iron but cant
incorporate it into Hgb
- iron accumulates in
mitochondria of RBC
defective heme synthesis
- inherited, acquired, or
idiopathic
-aka cobalamin
- 2000-5000 mcg of stored
B12 in liver
- takes 3+ yrs to become
deficient
Causes:
-inadequate intake
- Malabsorption:
Inadequate production of
IF = 70% (pernicious
anemia, gastrectomy
Disorder of terminal
ileum: celiac, enteritis,
resection, neoplasm,
Crohns
Competition of B12 in gut:
fish tapeworm (rare)
Drugs: colchicine,
neomycin
Hereditary autoimmune
dz
-pts lack intrinsic factor
necessary for B12
absorption in GI tract
-inadequate intake =
alcoholics, teens, elderly
(most common cause)
- increase requirements =
pregnancy, lactation,
infancy, malignancy,
chronic hemolytic anemia,
hemodialysis

-No specific clinical


futures other than related
to anemia: pallor, fatigue

- rule out malignancy


(MDS, leukemia)
-

-glossitis
- pallor
- anorexia
- diarrhea
- peripheral neuropathy:
stocking-glove
paresthesias, vibration
and position sense,
progress to abnormal
balance and dementia

-anemia = mild to
moderate
- normo or microcytic
- serum iron = high
- bone marrow shows
ringed sideroblasts/iron
stain increased

-transfusions when
necessary
-chelation prn
-tx depends on the cause
- remove offending agent
(alcohol, lead, drug)
- Vit B6 may be helpful

Contributors: Alcohol,
lead,
myelodysplasia/leukemia,
TB, drugs

-macrocytic = MCV 110140


- severe anemia with
coexisting
thrombocytopenia and
leukopenia
- peripheral smear =
hypersegmented
neutrophils
- retic = low
- serum B12 = low (<170
pg/mL = anemia,
<100pg/mL =
symptomatic)

- replacement therapy:
oral, parenteral, nasal
- parenterally: front load
doses with maintenance
monthly for life
- oral dose
- response is brisk =
normal CBC in 2 months
- Schillings test = rare
today
- assay for antiparietal cell
antibodies

-B12 not synthesized in


body
- foods of animal origin:
meat, dairy, eggs
-binds with Intrinsic
Factor (IF), secreted by
gastric parietal cells
- B12-IF complex
absorbed in terminal
ileum & stored in liver

-Replacement therapy
with folic acid po daily
- higher doses necessary if
malabsorption issues exist
- quick response = 1-2
month correction
- therapy duration
depends on the cause of
the deficiency

-Important for DNA


synthesis
- fruits and veggies =
primary dietary source
- daily requirement =
50mcg (more in
pregnancy)
- body stores are 5-20mg
deficiency in months

B12 deficiency

-malnourished
appearance
- diarrhea
- cheilosis
- glossitis
- NO neurologic
symptoms

- RBC folate < 150ng/mL =


diagnostic

-labs similar to B12


deficiency
-macrocytosis
- normal B12 lvs
- RBC folate < 150ng/mL
(RBC folate is better than
serum folate b/c it is not
subject to fluctuations
based on intake)

Not compiled by Drew Murphy

Hematology
- malabsorption = GI
diseases, drugs
(phenytoin, sulfa)
- Impaired metabolism =
alcohol, methatrexate

Pure Red
Cell Aplasia

Aplastic
Anemia

- hemolytic anemia will


need therapy indefinitely
- multivitamin

-usually idiopathic & rare


- autoimmune dz
mediated by T
lymphocytes or (rarely)
IgG antibody against
erythroid precursors

-symptoms associated
with anemia which is
often severe

-bone marrow failure,


arising from injury or
suppression of
hematopoietic stem cell
pancytopenia
Acquired = drugs
(phenytoin,
sulfonamides),
chemotherapy, radiation,
chemicals (benzene,
solvents, insecticides),
viruses (HIV, EBV),
pregnancy (SLE, PNH)
Hereditary (rare):
Fanconis anemia
Idiopathic = 50-60%
(autoimmune)

-occurs at any age: most


common in young adults
(20-25) or >60
- male:female ratio similar
- incidence in western
countries is 1-5
cases/million
persons/year (1000
diagnosed per year in US)
- abrupt onset or insidious
- significant pancytopenia
fatigue, weakness,
dyspnea, excess
bleeding/bruising,
petechiae, purpura,
pallor, infections
- NO hepatosplenomegaly
or lymphadenopathy

-retic = low/absent
- normal morphology
- WBC and platelets = not
affected
- bone marrow =
normocellular (erythroid
precursors are reduced or
absent)
Hallmark = Pancytopenia
Impt to distinguish from
other causes of
pancytopenia
1. MDS or acute
leukemias abnormal
cells in bone marrow,
increase blasts
2. Hairy cell leukemia
splenomegaly & abnormal
lymphoid cells on bone
marrow
3. Normocellular marrow
& pancytopenia SLE,
hypersplenism,
disseminated infection

-anemia may be severe


- retic = low
- morphology and MCV =
normal
- bone marrow =
hypocellular, but no
abnormal cells seen

- stop potential offending


medications
- resection of thymoma if
present
- high dose IV
immunoglobulin (if viral
associated)
- immunosuppressive
therapy = #1 choice
- mild =
monitor/supportive care,
transfusions, treat
infections
- severe disease (ANC <
500, plts<20, anemia
w/retic<1%)
- bone marrow transplant
(under age 50) =
allogentic transplant from
HLA-matched sibling is
potentially curative
- only 25-30% of pts will
have a matched sibling
- immunosuppression: if
not a transplant candidate
or s/out a match

- methotrexate, sulfa &


other drugs interfere with
metabolism of folate
- Alcohol = common
precipitator of folate
deficiency (impaired
hepatic function/defective
diet/poor or absent tissue
stores due to long
standing alcoholism)
Can be associated with
thymoma, lymphoma,
lupus, CLL, viral infections(
transient episodes), drugs
(phenytoin)

- untreated severe disease


= 3 month survival w/20%
alive at 1yr
- bone marrow transplant
offers 60-90% cure in
HLA-matched donors
- partial remissions
w/immunosuppression in
60-80% of pts
-1/3 will relapse and 2050% will develop MDS

Not compiled by Drew Murphy

Hematology
Macrocytic
Anemia

Normocytic

RBC
Destruction:
Hemorrhage
RBC
Destruction:
Hemolysis

Causes:
-B12, Folate, Thiamine,
Diet, Alcoholism
-Inherited/GI
- Chemo
Drugs/Spleenectomy
- Erythroleukemia/LeschNyhan
- E Hypothyroid
- Liver dx
- Reticulocytosis
Causes:
-Normal preg or lactation
-over hydration
-Renal
- Marrow infiltration
- Acute blood loss
- liver Dz
- Endocrine Dz/zero
production
- systemic inflammation
(anemia chronic illness
70%)
-Hemorrhage = acute
blood loss bone
marrow stimulates
release of stored platelets
and WBCs
- no anemia
- No stoarage reservoir of
RBCs in bone marrow
takes several days to
weeks to replenish RBCs
-Hemolysis = shortened
RBC survival: severity
dependent on rate of
destruction & bone
marrow response
- RBCs are destroyed
(continuously or
episodically)

-look at family Hx

-Coombs test
- peripheral blood smear:
Heinz bodies, sickle cells,
parasites
- Hgb electrophoresis

- Erythropoietin s by 6
hrs
- reticulocytosis w/in 24
hrs

- HR increases,
extravascular fluid shift
results in anemia due to
the dilution effect

-Haptoglobin = low
-Lactate Dehydrogenase
LDH lvs = high
- indirect bilirubin = high
- retic=high = bone
marrows response to
RBCs

Haptoglobin: glycoprotein
produced in the liver, binds
circulating free Ggb after
hemolysis occurs so lvs are
sed following hemolytic
episodes
-haptoglobin non-specific
acute phase reactant

Not compiled by Drew Murphy

Hematology
- bone marrow cant keep
up w/destruction
anemia

Hereditary
Spherocytosis

Paroxysmal
Nocturnal
Hemoglobinuria
(PND)

G6PD:
Glucose-6Phosphate
Dehydrogenase
Deficiency

-Hemolytic Anemia:
Intrinsic
- inherited abnormality of
RBC membrane
- loss of RBC surface
integrity defective cell
membrane protein
(spectrin)
-RBCs prone to rupture in
microvasculature or
spleen
-Hemolytic Anemia:
Intrinsic
- varying degree of
anemia (pitted RBCs)
- acquired stem cell
disorder: RBC membrane
= prone to lysis by
complement
- all stem cell lines can be
affected

-Hemolytic Anemia:
Intrinsic
- hereditary enzyme
defect episodic
hemolysis
- absence of G6PD makes
RBCs sensitive to
oxidation
- oxidized Hgb denatures
to Heinz Bodies
damage to RBC

Intrinsic: internal defect of


RBC membrane, enzyme
system, hemoglobin (most =
hereditary)
-Extrinsic: defect cause by
external factor (autoimmune,
drugs, infection or trauma)
often acquired

- hemoglobin normal or

- Clinical triad of anemia,


splenomegaly and
jaundice
- pigment type gallstones
may be present
- chronic leg ulcers

-spherical shaped RBCs =


Spherocytes

-microcytic
-mild to moderate anemia
- anemia may be absent:
bone marrow can
compensate except in
times of stress (ex
infection)
-retic = high
- Indirect bilirubin = high
-Neg coombs test

- folic acid po daily


- splenectomy for sever,
symptomatic pts
RBC survival

-3 common
manifestations
1. episodic hemolytic
anemia
2. thrombosis
3. pancytopenia
increased risk of MDS,
aplasia, leukemias
-25% exhibit
hemoglobinuria (episodic
and usually first morning
urine) = due to episodic
hemolysis
-affects more than 200mill
- mostly men
- X-linked recessive
- female carriers rarely
affected
- usually healthy
- No splenomegaly
- episodic hemolysis
triggered by oxidative
stress (acute infection,

- confirmed by flow
cytometry assay :
absence/deficiency of
CD59 or CD55 proteins
- anemia is variable =
normocytic, unless iron
deficiency is present

-normocytic anemia
unless associated w/iron
deficiency =
microcytic/hypochromic
- WBCs and platelets can
be affected as well (low
counts)
- +/- reticulocytosis

-treat iron deficiency


-transfusion prn
- prednisone to
hemolysis
- bone marrow transplant
in young pts
- Anti-complement Ab
(eculizumab) reduce
hemolysis, thrombosis &
transfusion reqs

-peripheral smears may


be normal b/w hemolytic
episodes
Following an episode
-retic= high
- indirect bilirubin = high
- G6PD specific enzyme
assay (may be false
normal directly following
hemolytic episode)

- no specific tx
- avoid oxidative stressors
- splenectomy for severe
cases
- transfusions prn (rarely
needed)
- inform all providers of
condition

-mild microcytic anemia


from chronic hemolysis
- spherocytes appear
hyperchromic and high
MCHC
- loss of biconcave disc
shape = lack of flexibility
- RBC fragility
- destruction in spleen or
microvasculature

-Resistance to malaria
-fava beans = trigger

Not compiled by Drew Murphy

Hematology
membrane and removal
by spleen (bite cells)

Sickle Cell
Anemia

SS trait =
AS

-Hemoglobinopathy
-Hemolytic Anemia:
intrinsic
- autosomal recessive
disorder with abnormal
Hgb chronic hemolytic
anemia
- abnormal HbS chronic
hemolysis
- sickling = reversible but
after repeat episodes, cell
permanently sickles
- rate of sickling depends
on [HbS], dehydration,
presence of HbF,
hypoxemia, and acidosis

No anemia
Rare crises except for
extreme conditions

acidosis, drugs: sulfa,


antimalarials, aspirin)
- episodes usually selflimited

- HbS gene carried by 8%


of AA
- seen around age 1 when
HbF normally falls
- pallor, jaundice,
splenomegaly, lower leg
ulcers, pigment
gallstones, priapism,
delayed puberty, infection
- Acute Episodes =
infarctive/pain crisis
cluster of sickled cells
occlude microvasculature
or organs, hours to days in
duration, skeletal pain
fever
Spontaneous or provoked
infection, folate def,
hypoxia, dehydration

- normal clinically
- risk of renal disease

repeat testing 2-3 weeks


post episode
- chronic low lvs of
enzyme in sever cases
-moth/bite cells
- Heinz Bodies

- differential = sickle cells,


target cells, Howell-Jolly
bodies (DNA fragments),
nucleated RBCs
- Hgb electrophoresis is
confirmatory for SS
HbA = 0%
HbS = 86-98%
HbA2 = 1-3%
HbF = 5-15%

-chronic hemolytic anemia


- persistency of HgF
- indirect bilirubin = high
- reticulocytosis
- leukocytosis and
thrombocytosis
- Sickledex: solubility
screen HbS precipitates
- cant distinguish b/w AS
and SS
- Neg screen reflect < 10%
HgbS
- Ped < 3 months may
have false neg results due
to high Hgb F lvs

- newborn screening
- supportive/preventative
- folic acid daily
- pt ed: altitude, hydration
& prompt treatment of
infections
- vaccinate: pneumonia,
flu & meningitis
- transfuse: only if
symptomatic (exchange
transfusions)
- pain crises: fluids, O2,
narcotics, antibiotics
- frequent pain crises: use
hydroxyurea to increase
HbF lvs

Normal peripheral smear


-40% HbS

- genetic counseling
- no treatment necessary

- Sickle cell trait (AS) =


carrier state 8%
- Sickle cell Anemia (SS) =
1/400
-AA = normal = 0% HbS
- AS = sickle trait = 40%
HbS
- SS = SS anemia/disease =
86-98% HbS and increase
HbF
- vascular occlusion
infarction
1. pulmonary (acute chest
syndrome)
2. retinal blindness
3. renal renal failure
4. stroke (children)
5. splenic infarctions
splenectomy
6. aspectic necrosis of
femoral head infection

Not compiled by Drew Murphy

Hematology
Hemoglobin
C Disorders

Autoimmune
Hemolytic
Anemia

Extracellular
Non-Immune

Spurious or
Relative
Erythrocytosis

-extrinsic hemolytic
anemia
-acquired anemia: IgG
antibody binds to RBC cell
membrane (usually
directed against an Rh
antibody)
- macrophages attack
RBC/IgG complex cell
membrane removed =
spherocyte
-rarely drug induced
-hemolytic anemia:
extrinsic
-traumatic angiopathies
- RBCs encounter physical
obstacles (fibrin strands,
clots, or defective native
cardiac valves or
prosthetic valves)
-normal RBC mass in
decreased plasma volume
- hemoconcentration
secondary to dehydration
-causes: diuretics, H2O
deprivation, diaphoresis,
diarrhea, emesis, ethanol,
hypertension,
pheochromocytoma, preeclampsia

-50% = idiopathic
- also seen with lupus,
NHL, CLL
- occurs at all ages
- women> men
- anemia can be rapid
onset and severe
- fatigue, angina or CHF,
jaundice, splenomegaly

-intrinsic hemolytic
anemia
- AC carrier state
asymptomatic 2-3% of AA
- no anemia/normal RBC
survival
-SC milder clinical
course than SS (1:833)
-CC mild hemolytic
anemia
-Coombs test = positive
Direct: antibody on RBC
surface (+)
Indirect: free antibody in
the serum (+/-)

Hallmark = target cells


and HgB crystals
-Hgb electrophoresis =
diagnostic

Hgb 6-10 g/dL = severe


anemia
- reticulocytosis
- peripheral smear:
spherocytes
- indirect bili = high

- prednisone until counts


recover (slow taper)
-possible chronic therapy
with lowest possible dose
- splenectomy
- Drugs: Retuximab,
Danazol,
immunosuppressants,
IVIG
-avoid transfusions if
possible

-50% are idiopathic


- many caused by other
illnesses = lupus, Chronic
Lymphocytic Leukemia
(CLL), lymphoma,
infection

-Hallmark = Schistocytes =
RBC fragments due to
mechanical injury to RBCs

Not compiled by Drew Murphy

Hematology
Secondary
Erythrocytosis

-excess production of
RBCs
- normal response:
erythropoietin produced
in response to hypoxia
- secondary
polycythemia: high
altitude, COPD, low
cardiac output, CO
poisoning, renal disorders
-excess production of RBC
for no apparent purpose

Hallmark = elevated HCT


+ JAK2 mutation =
confirmatory

Polycythemia
Vera

Cold
Agglutinin
Disease

Hemochromatosis

- acquired hemolytic
anemia
- due to IgM antibody
- reacts w/cells at 37C or
lower
- blood goes to
extremities, IgM binds
w/complement RBC
destroyed in liver
- most cases = idiopathic
- can be associated
w/neoplasm or postinfection
- iron overload
- hereditary (autosomal
recessive C282Y mutation)
- 1:10 US Caucasians have
mutation
- 1:400 are homozygous
-Men> women clinical
symptoms
- iron accumulation in
liver, pancreas, heart,
kidneys
- alcohol or obesity

- anemia is rarely sever


- mottled or numb
fingers/toes
- episodic hemoglobinuria
on exposure to cold

- often asymptomatic
- onset after age 50
- fatigue
- arthralgias
- hepatomegaly
- skin pigmentation
(bronze)
- cardiomegaly (+/-)
failure
- diabetes
- impotence

- Liver biopsy confirms dx

-normocytic
normochromic
morphology
- WBC and platelets =
elevated in 50% of pts
B12 = high
- reticulocytosis
- peripheral smear shows
spherocytes
- Coombs test (+) for
complement
- positive cold agglutinin
test = chilled blood
appears clumped

- avoid exposure to cold


- no splenectomy or
steroids
- Rituximab = tx of choice
- immunosuppressives for
severe cases

LFT = high
- serum iron = high
- serum ferritin = high
(women may be normal)
- test for C282Y mutation

- avoid iron rich food, vit C


supp & alcohol
- phlebotomy to deplete
iron stores
- iron chelators
- treat organ damage
- genetic testing for family

Not compiled by Drew Murphy

Hematology
Hemosiderosis

Neutropenia

Myeloproliferative
Disorders

Polycythemia
Vera

- iatrogenic iron overload


- due to multiple
transfusions (usually 100
units of RBCs)
- body cant excrete iron
organ damage
- neutrophil count of
<1500/mcL
- lower ANC = greater risk
for serious lifethreatening infection

- common in pts
w/thalassemia

-AA pop may have lower


ANC as a normal variant
(1200/mcL)
- stomatitis
- fever (not reliable
indicator of infection in
severe neutropenia)
- sever infection:
septicemia, pneumonia,
cellulitis
- bacterial and fungal

- treat w/ iron chelators

CBC w/diff
- bone marrow biopsy:
distinguish bone marrow
failure, myelodysplasia,
drug effect

- discontinue potential
causative agent
- educate pt
- neutropenic precautions
- treat infections w/broadspectrum antibiotics
(gram neg enteric
bacteria)
- growth factors (G-CSF) in
severe cases or due to
chemotherapy

- heterogenous disorders
- cellular proliferation of
one or more hematologic
cell lines in peripheral
blood
- distinct form of leukemia

Clonal myeloproliferative
disorder
- characterized by
[Hgb] and RBC mass
(erythrocytosis)
- primary polycythemia =
true in RBC mass
- Secondary Polycythemia
= hypoxia, renal disease,
MIs, dehydration

- tinnitus
- vertigo
- headaches
- visual disturbances
- thromboses
- dyspnea
- night sweats
- pruritus/erythema
- plethora
- fullness of head and face
- weakness/fatigue

Hemoglobin:
Men > 18.5 g/dL
Women > 16.5 g/dL
- elevated RBC mass
- JAK2 mutation

Bone marrow
hypercellular
- erythroid, granulocytic,
megakaryocytic
proliferation
- serum Epo = low (kidney
is sending normal signals)

- referral to HematologistOncologist
- therapeutic
phlebotomies, keep Hct <
44%
- myelosuppression
(hydroxyurea)

- 1000 -1500 no significant


impairment
- 500-1000 = alert pt to
slightly increase risk
- below 500 risk rises
sharply
- prognosis depends on
underlying cause

4 types
- chronic myelogenous
leukemia (CML) = WBC
line
- polycythemia vera (PV)
- Essential
thrombocythemia (ET) =
platelets
- myelofibrosis = scaring
of bone marrow
- risk of cardiovascular
events, thrombotic events
- transformation to AML
or primary myelofibrosis
- treated survival = 10-16
yrs
- untreated survival = 1.5
yrs
- average diagnosis @
60y/o
- more males than
females
- 10-15% evolve into AML
- 10-30% evolve into
myelofibrosis

Not compiled by Drew Murphy

Hematology

Essential
Thrombocytosis

Myelofibrosis

Immunoproliferative
Diseases

Waldenstrons
Macrogobulinemia

-nonreactive, chronic,
myeloproliferative
disorder
- sustain megakaryocyte
proliferation in
platelets (> 600,000)
- unclear cause
- normal platelet survival

Myeloproliferative
disorder
- morphologic
abnormalities in two or
more hematopoietic cell
lines
- chronic
- idiopathic
- bone marrow fibrosis

- Waldenstroms
macroglobinemia
- Multiple Myeloma
- Monoclonal
Gammopathy of
Uncertain Significance
(MGUS)
- chronic malignant
lymphoproliferative
monoclonal gammopathy
- lymphoplasmacytic
lymphoma
- environmental, familial,
genetic, viral factors

-1/3 are asymptomatic


-2/3 with neurologic
symptoms, thrombosis,
bleeding, constitutional
symptoms, pregnancy
complications
- neurologic = Dysarthria,
Dysphoria, vertigo,
dizziness, migraine,
syncope, scotoma,
seizures
- Bleeding
- plenomegaly/hepatomegaly
- most = asymptomatic
- splenomegaly
- anemia, leukopenia,
thrombocytopenia
increased bruising and
bleeding
- anemia and related
symptoms
- fever
- night sweats
- bone pain

- 50% JAK 2 positive


- negative result doesnt
rule out thrombocytosis
- platelet aggregation
studies show impaired
aggregation

Pt/PTT = normal
- girant platelets on smear
- leukocytosis,
erythrocytosis, mild
anemia
- elevated platelet count >
600,000
- normal platelet funt &
life span
- WBC = high
- RBC = normal
- megakaryocytes

- reduce risk factors:


obesity, smoking,
hypertension,
hypercholesterolemia
- medications: anagrelide,
hydroxyurea, low dose
aspirin
- treatment modalities =
plateletpheresis

-Primary (essential)
Thrombocytosis
- Secondary (reactive):
severe hemorrhage, IDA,
s/p surgery, s/p
splenectomy, malignant
neoplasms, chronic
inflammatory disease,
acute infections, B12
deficiency, drugs, ETOH

- JAK2 positive
- excessive
collagen/reticulin fibers
- abd US or CT=
hepatosplenomegaly
- normocytic anemia,
thrombocytopenia,
leukocytosis w/ a left shift

- leukoerythroblastic
blood film
- giant platelets and
teardrop poikilocytosis
- hypercellular bone
marrow
- reticulin/collagen
fibrosis
cytopenia with
hypercellular bone
marrow
- leukoerythroblastic
anemia

- observation
- supportive
(transfusions, IVIG,
immunizations, epo)
- JAK inhibitors = drugs
- allogenic transplant
- splenectomy/radiation

- cytogenic abnormalities
- ineffective
hematopoiesis
- preleukemia
- occurs in 10-30% of pt
with polycythemia
- peak incidence = 50-70
yrs
- survival = 10 yrs

- similar presentation to
multiple myeloma
- organomegaly common
(not in MM)
- lytic bony disease and
renal disease are
uncommon -seen in MM
- hyperviscosity syndrome
- bullous skin disease

- high lv of serum IgM


- elevated serum viscosity
- lymphoplasmacytic
infiltrates in bone marrow
- CT scan

- excess B & plasma cells


- monoclonal antibody
spike (IgM, hence macro)
- SPEP = M-spike
- UPEP = Bence Jones
- CBC: RBCs=high, PLT =
low, anemia
- rouleaux
- ESR = high

- no treatment indicated
for asymptomatic disease
- monoclonal antibody
therapy (rituximab, antiCD20)
- chemo
- combination therapy
- plasmapheresis
- BMT

- mean survival = 78
months
- poor prognosis if older
than 65, HgG < 10g/dL,
albumin < 2 g/dL.,
elevated beta-2microglobulin lV

Not compiled by Drew Murphy

Hematology

Multiple
Myeloma

- proliferation of
malignant plasma cells
- exposures in food
industries
- herbicides/insecticides
- benzene and solenvts
- > 20 yr exposure to hair
dye
-no hereditary etiology

- plasma cell dyscrasias

MGUS:
Monoclonal
Gammopathy
of Unknown
Significance

Leukemias

- heterogeneous
neoplastic disorders of
WBCs
- 2 types = myeloid,
lymphoid

- livedo reticularis
- chronic urticaria
- cutaneous plaques and
nodules
- acrocyanosis
- collection in bone
marrow = myeloma
- multiple collections =
multiple myeloma
- soft tissue masses =
plasmacytomas/lytic
lesions in the skeleton
- bone pain, renal failure,
spinal cord compression
- pallor (anemia),
ecchymoses or purpura,
cardiomegaly
- Shoulder pad sign
- macroglossia
- asymptomatic
- neuropathies
- no specific PE
abnormalities
- polyneuropathies

Look at
- morphology of WBCs
- cytochemistry (special
stains)
- genetic analysis
(chromosomal, molecular)
- immunology/serology

- LDH, uric acid, Ca,


creatinine = high

- overproduction of
monoclonal paraprotein
(M protein or M-spike)
- SPEP (Mspike)
- 24 hr UPEP (bence jones
protein)
- skeletal survey (lytic
lesions)
- rouleaux formation of
plasma cells

- anemia
- hypercalcemia
- monoclonal spike in IgG
&/or IgA on SPEP
- monoclonal proteins on
UPEP (Bence-Jones
proteins
- lytic lesions on skeletal
radiograph
- CBC
- bUN/creatinine (renal
insufficiency)
- hyperviscosity

- multiple therapies
- no cure
- chemotherapy
- autologous BMT
- high dose
chemotherapy/BMT:
>50% survival at 5 yrs

- 5 yr survival = 25%
- AA> Caucasians

- M-protein (M-spike)
- serum and urine w/out
evidence of Multiple
Myeloma
<10% plasma cells
- no or small amts. Of
Bence-Jones protein
- absence of lytic bone
lesions
- no related anemia,
hypercalcemia, renal
failure, end organ damage
- blasts on bone marrow
- most often presents as
blasts in peripheral blood
- CLLs & CMLs =
characterized by gradually
increasing numbers of
mature cells in marrow
- presence of
immature/abnormal cells
in bone marrow and
peripheral blood

- chem. Panel
- CBC
- Beta-2 microglobulin
- SPEP
- 24 hour UPEP
- bone marrow biopsy

- no treatment
recommended
-

- probably precursor to
multiple myeloma
- may persist for yrs
- SPEP IgG moderately
elevated

- WBC = high
PLT = low (acute)
NL = low (chronic)
- Hct/Hgb = normocytic
normochromic anemia

Not compiled by Drew Murphy

Hematology
- disease of leukocytes
and their precursors

- rapid onset w/symptoms


common
- hemorrhage
- infection
- infiltration of organs

Malignant cells =
lymphoid precursor cells
- chromosomal
translocation

- no identifiable risk
factors
- usually in adults > 60
- anemia, pallor, cardiac
flow murmur, fever,
infection,
thrombocytopenia,
petechiae, ecchymosis
(can indicate DIC),
lymphadenopathy, rash
- death due to
uncontrolled
infection/hemorrhage
-symptoms from bone
marrow failure, organ
infiltration, leukemic cells
- onset @ 70 yrs
- anemia, pallor, cardiac
flow murmur, fever,
infection, petechiae,
ecchymoses, rash,
purpura, AMS, respiratory
distress

Acute
Leukemias

Acute
Lymphoblastic
Leukemia
(ALL)

Acute
Myelogenous
Leukemia
(AML)

Chronic
Leukemias

Disease of bone marrow


- myeloid precursors are
stopped at an early stage
anemia,
thrombocytopenia,
neutropenia, and also an
accumulation of bone
marrow, blood and often
the spleen and liver

- monoclonal disorder
- accumulation of
functionally incompetent
lymphocytes
3 Phases:
1. Chronic (mature cells
proliferate
2. Accelerated (additional
cytogenic abnormalities)

- slow onset
- asymptomatic
- disorders of middle age
- splenomegaly
- fever, weight loss,
malaise
- frequent infections
- bleeding/bruising
- thrombosis

- pancytopenia
w/circulating blasts
- bone marrow =
hypercellular &
dominated by blasts
- immature/abnormal
cells in bone marrow and
periphery
>30% blasts in marrow
- pancytopenia
- B-cell precursor = poor
prognosis
- leukopenia
- coag studies = abnormal
- PT, fibrinogen, and
D-dimer
- circulating blasts
- schistocytes w/DIC
- LDH and uric acid = high
- CT scan
- cardiac monitoring/EF
CBC: anemia,
thrombocytopenia
WBC: Leuks, normal
counts or leukopenia
DIC: common ( PT,
fibrinogen & D-dimer)
Smear: circulating blasts,
schistocytes w/DIC
- Auer Rods
- Lactic dehydrogenase,
uric acid = high
- caused by mutation =
Philadelphia chromosome
(BCR_ABL)

- CBC: absolute
lymphocytosis
- WBC = 20,000-60,000
cells
- blood smear:
lymphocytosis
- smudge cells
- peripheral blood flow
cytometry

- classified according to:


morphologic,
cytochemical, and
immunologic criteria
- acute lymphocytic leuk
- acute Myelogenous Leuk

- Allogeneic transplant for


adults
- induction chemotherapy
- complete remissions in
65-85% of pts
- consolidation therapy
- maintenance therapy
- CNS prophylaxis =
Ommaya (chemo directly
into spinal fluid)

-Immunologic
phenotypes: common,
early B lineage, T cell
- histochemical stains
- most common type of
cancer and leukemia in
kids
- 20-40% cure rate

- Induction chemotherapy
- granulocyte stimulating
factor
- pt considered for clinical
trials otherwise standard
therapy
- MUGA (multiple-gated
acquisition) scan or echo
to assess ejection fraction
(EF)
- Consolidation Therapy:
allo/auto BMT
- treat when symptomatic
- watchful waiting
- chemotherapy
- immunologic therapy
- combination therapy
- allogenic BMT = curative
- Gleevec = very
successful!

- usually no identifiable
risk factors
- risk factors: hematologic
disorders, familiar
syndromes (down
syndrome),
environmental exposures,
drug exposures

- some are similar to


acute leukemias = enter a
blast phase
- most common form of
leukemia
- Life expectancy: 5-10
Rai-Sawitsky staging
system:

Not compiled by Drew Murphy

Hematology
3. Blast (immature cells
rapidly proliferat)

- lymphadenopathy
- Mucocutaneous
bleeding/petechiae
- gripping splenic
infarction
-bone pain (blast phase)
- funduscopic:
papilledema, venous
obstruction, etc

- serum quant IgG


- uric acid to rule out
hyperuricemia

- WBC
- left-shifted myeloid
series
- low % pros and blasts
- Philadelphia
chromosome or bcr/abl
gene present
- RBCs normal, no anemia
- isolated lymphocytosis
- coexpression of CD19,
CD5

Chronic
Myelogenous
Leukemia
(CML)
Chronic
Lymphocytic
Leukemia (CLL)

Hairy Cell
Leukemia

Hodgkins
Disease

Low risk lymphocytosis


in blood and marrow
Intermediate risk:
lymphocytosis w/enlarged
nodes
- High risk: lymphocytosis
w/anemia or
thrombocytopenia

- clonal malignancy of B
lymphocytes

- hypogammaglobulinemia

- chronic B-cell lymphoid


leukemia
- infiltration of
reticuloendotherlial
system and bone marrow
pancytopenia
Possible etiologies:
benzene, insecticides,
solvents, radiation, wood
dust, hx of mononucleosis

- lymphoma
Arises from lymph tissue
- etiology: unkown
- EBC may be involved
- Males>females

- weakness/fatigue
(anemia)
- 1/3 w/bleeding
(thrombocytopenia)
- 1/3 w/ fever and
infections (neutropenia)
- abdominal
pain(splenomegaly)
- weight loss
- night sweats
- bacterial infections
- opportunistic infections
- lymphadenopathy
- fever, chest pain, cough,
SOB, pruritus, back/cone
pain, nodal pain, Bsymptoms, asymptomatic
lymphadenopathy
(rubbery)

- abnormalities of chrom 5
= 40% of pts

- Lymph cytoplasm= Fried


egg appearance
- CBC: pancytopenia
- anemia
- PLT & neutropenia
- bone marrow = dry tap

-10% never require


therapy
- blood transfusions: HbG
<10g/dL, Platelets<
50,000/mL, ANC< 500/mL

- 2% of leukemia
- commonly in whites
- middle age onset

- chemotherapy
- monoclonal antibodies
- alpha interferon

- lymph node biopsy


- Reed-Sternberg cell
looks like an owl/alien
- popcorn cells

-CT/PET
- lymph node biopsy
- bone marrow biopsy
- CBC
- Erythrocyte
sedimentation rat = high =
worse prognosis

- induction chemotherapy
- salvage chemotherapy
- radiation
- auto/allo transplant

- 5 subtypes
- bimodal distribution
- 5 yr survival = 90%
- asymptomatic
adenopathy

Not compiled by Drew Murphy

Hematology
NonHodgkins
Disease
High-grade
NonHodgkins
Lymphoma
Infectious
Diseases
w/WBC
findings

Lymphomas
- abnormal lymphocytes
in lymph nodes, bone
marrow, extranodal sites
- B-cell lymphomas = most
prevalent
- > 50 subtypes
-lymphoblastic lymphoma

- lymph node biopsy for


Dx and staging
- B-cells, T-cells, NK cells

- Lactate dehydrogenase
(LDH) = high
-peripheral blood may be
normal
- some leukemic phase
- serum LDH

Ann Arbor Staging:


I. tumor on one side of
diaphragm
II. tumors on one side of
diaphragm
III. groups on both sides of
diaphragm
IV. organs outside lymph

- monoclonal antibody
(rituximab, CD20 antigen)
- chemotherapy
- watchful waiting
- BMT

- may respond quickly to


therapy

- 5 yr survival = 63%
- Low-grade NHL: marginal
zone lymphoma, MALT,
Follicular lymphoma,
mantle cell lymphoma
- many remissions
- 5 yr survival = 63%
- large bulky adenopathy
- Burkitts lymphoma
- live expectancy < 2yts

- Infectious
Mononucleosis
- Ehrlichiosis
- Histoplasmosis
-HIB

- caused by Epstein-Barr
virus (EBV)

Infectious
Mononucleosis
- tick-borne bacteria

Ehrlichiosis

- SVC syndrome: extra


fluid
- fever
- night sweats
- pruritis
- weight loss
- splenohepatomegaly
- enlarged lymph nodes
that mimic infection
- skin lesions
- night sweats, fevers,
pruritis,
lymphadenopathy, weight
loss, SOB, cough,
abdominal pain, N/v,
constipation, early satiety,
headaches, personality
changes, seizures

- Lymphocyte
pleomorphism on blood
film w/lymphocytosis
>10% reactive
lymphocytes
- EBV Titer
- heterophile Ab
- bone marrow = normal
- clustered bacteria in
vacuoles in neutrophils,
monocytes, macrophages
- thrombocytopenia
- leukopenia w/left shift

Not compiled by Drew Murphy

Hematology
Histoplasmosis

Myelodysplastic
Syndrome
(MDS)

- intracellular fungus
-Histoplasma capsulatum
- usually
w/immunocompromised
pts
-10,000 new cases yearly
in US
- median age > 60
- male predominance
- exposure to benzene,
radiation, tobacco, and
chemotherapeutic agents
( MDS)
- genetic abnormality:
trisomy 21, Fanconis
anemia, Blooms
syndrome, and ataxia
telangiectasia
paroxysmal nocturnal
hemoglobinuria
- congenital neutropenia
- primary: no know
exposures
- secondary: prior
treatments of cancers
- sudden decrease in
platelet count: many
causes

Acute
Thrombocytopenia

Idiopathic
Thrombocytopenic
Purpura

- rising Ab
immunofluorescence titer
- Wright-Giemsa shows
organism in neutrophils &
monocytes
- organism in
macrophages on bone
marrow smear
CBC, iron studies,
Coombs, LDH,
Haptoglobin,
Vit B12
- bone marrow biopsy
w/cytogenetics
- platelets = low
- megakaryocyte
fragments
- ringed sideroblasts (due
to iron accumulation in
mitochondria)

- auto-immune antibodies
form and alter platelets
- platelet removal by
spleen
- unknown cause

- preceded by macrocytic
anemia w/mild
thrombocytopenia or
neutropenia
- anemia = mild to severe
- fatigue/malaise
- CHF
- petechiae, ecchymoses,
epitaxis, gingival bleeding
- fever/infections w/
neutropenia (mild to
severe)

- bleeding/bruising
- chemo/quinine
- autoimmunity
- alcohol
menorrhagia/metrorrhagi
a
- splenomegaly
- petechia
Physical exam: same as
acute thrombocytopenia

- based on H&P

- platelet count = low


<150
(spontaneous bleeding
<20)

Dx of exclusion

Coag labs should be


normal
- normal PT/PTT
- normal bone marrow
- spleen normal

- supportive Care:
RBC/platelet
transfusions,
erythropoietin
- Drugs: Vidaza, Dacogen,
Revlimid
- allogeneic BMT

5 subtypes
- refractory anemia with
ringed sideroblasts
- refractory anemia
- chronic myelomonocytic
leukemia
- refractory anemia with
excess blasts
- refractory anemia
w/excess blasts in
transformation

- immunosuppression:
steroid!, Rituximab,
cyclophosphamide
- Immune Modulation:
IVIg, splenectomy

- treatment goal =
elimination of antibodies
- platelet transfusion if
acute bleed
- steroids: prednisone

Not compiled by Drew Murphy

Hematology
- increased bone marrow
production, but cant keep
up with destruction

Heparin Induced
Thrombocytopenia

2 Types:
1. transient decrease in
platelet count
2. immune-mediated: very
serious!
- heparin combines
w/Platelet factor 4
immunogenic complex
- heparin, PF4 and
antibodies platelet
activation limb & lifethreatening thrombosis
Disorder of Von
Willebrand Factor
processing

- inflammation/necrosis &
subcutaneous sites
- limb asymmetry? Clot?
- clood/pulseless
extremities

Hx: heparin for 4-10 days


- other causes excluded
- confirmation
w/functional assay
(serotonin release assay)
- platelet drop of 50%
- thrombocytopenia after
5-10 days of heparin
- thrombosis: high risk

- intra-vascular platelet
aggregation
- systemic
manifestations:
CNS, renal, cardiac,
hematologic

- micro-angiopathic
hemolytic anemia = Hallmark
HPI: mental status changes,
symptoms correlating to endorgan damage
- exclude other diagnoses
particularly DIC
- same as acute/idiopathic
thrombocytopenia

- related to TTP
- E. coli infections
- hemolysis, micro
thrombi to brain and
kidneys
- common in infants,
young kids, and pregnant
women

- similar to TTP
- infection diarrhea
- no mental status
changes/neurologic
symptoms

- no distinctive HUS lab


test

- use of anti-platelet
agents

- bleeding symptoms
- easy bruising

Thrombotic
Thrombocytopenic
Purpura

Hemolytic
Uremic
Syndrome
Drug
effects

- shistocytes
- many small blood clots
- abnormally high # of
platelets consumed
=count
- coags normal
- evidence of Heparin/PF4
antibody
- functional assay
- serological assay: ELISA

- Stimulation of Platelet
production: Eltrombapag,
Romiplostin

- stop all heparin


products
- treatment w/alternative
anti-coagulation therapy
Warfarin: initiate after
platelet counts are
normalized, 6-12 weeks
- can also use Coumadin
- begin a direct thrombin
inhibitor

- incidence is higher in
surgical pts
- arterial and venous
thrombosis may occur

- in ultra-high mol
weight multimers of von
Willebrand Factor
- Platelet count <20K
- coags = normal
- anemia
- hemolysis
- schistocytes
- elevated LDH
(hemolysis)
- same as TTP
- thrombocytopenia
>20,000
- normal PT/PTT &
fibrinogen
- elevated LDH
(hemolysis)
- schistocytes (HUS<TTP)
- Normal vWF enzyme
- severe decrease in
platelets

- plasma exchange
return RBCs to pt
- fresh plasma
- immune suppression

- association with certain


drugs

- supportive
- plasma exchange =
plasmapheresis
- symptomatic &
supportive
- antibiotics, BP control,
dialysis/transplant

Not compiled by Drew Murphy

Hematology
Liver
Disease
Warfarin
Therapy
Vitamin K
Deficiency

- coagulation disorder
- liver makes all the
clotting factors except
FVIII (8)

- splenomegaly
thrombocytopenia due to
spleen sequestration of
platelets & low lvs of
thrombopoietin

- Warfarin antagonized
action of Vit K
- Vit K is necessary for
Factors II, VII, IX, X and
also protein C and S
- similar to treatment
w/Warfarin
- Hemorrhagic Disease of
the newborn
- Malabsorption
- Malnutrition
- Extended antibiotic use

- can induce minor


bleeding

Deficiencies in
HMWK, PK,
and FXII

FXI
deficiency
FVIII, FIX
Deficiency
Hemophilia
A

-Biliary tract dz (interferes


w/absorption)

- prolonged PT
Distinguish b/w liver dz
and vit K deficiency:
- low lvs of 2, 7, 9, 10
- 5 is normal

- NO associated bleeding

- prolonged aPTT > 100


sec

- common in Jewish
ancestry

- variable association
w/bleeding

- occurs in males
- x-lined
- Hemophilia A and B

-spontaneous bleeding or
just with trauma
- acute hemarthrosis
- chronic hemarthrosis =
target joint
- spontaneous
hemarthroses

- x-linked recessive
inheritance
- only males affected

- prolonged PT due to
ed FVII
- aPTT prolongs due to
in other factors
To distinguish b/w Liver
dz and vit K deficiencylow lvs of all factors
except for 8
- 5 and 7 are low
- Prolonged PT

-Vit K dependent factors


(2, 7, 9, 10) + 5 = first to
be affected

-INR = 4.5-20: PO vit K,


omit 1-2 doses of warfarin
- INR>10:hold warfarin,
PO vit K
INR elevated/major bleed:
stop warfarin, IV Vit K, use
prothrombin complex
concentrates

- prolonged aPTT
- FVIII/FIX lvs decreased

- Factor replacement: VIII


- FVIII for Hemophilia A
- FIX for Hemophilia B

- prolonged PTT
- low FVIII lvs

- Factor replacement

-vit K dependent procoagulant Factors:


2,7,9,10)
- proteins C& S are also
Vit K dependent = natural
anticoagulants
- vit K not recommended
for slightly elevated INR

- Most common severe


bleeding disorder

Not compiled by Drew Murphy

Hematology
Hemophilia
B
Inhibitor to
FVIII

- Christmas Dz
- x-linked recessive, only
in males

- seen during pregnancy


and in elderly
- auto-antibody against
FVIII, preventing function
or clearance

Provoked spontaneous
bleeding

- defect in von Willebrand


Factor (VWF) quantity or
quality

- limited to
mucocutaneous bleeding
- bruising hx
- increased bleeding after
minor procedures
- hysterectomy for
bleeding
- menorrhagia

Von
Willebrand
Disease

Glanzmanns
Thrombasthenia

BernardSoulier
Syndrome

- low lvs FIX


- prolonged PTT

- rare autosomal recessive


- defect in IIb and IIIa
receptors on platelet
membrane prevent
aggregation
- Firbrionogen & cWf
unable to bind receptors
to form platelet bridge
- rare autosomal recessive
- reduced GPIb receptor
on platelet membrane
(primary VWF receptor)

Prolonged aPTT
- FVIII lvs
- doesnt correct w/mixing
study

- low lvs of vWF antigen &


activity

- Normal PT/aPTT
- low lvs of VWF antigen
- multimers ed
- platelet aggregation
studies
- platelet count = normal
or low
- platelet function assay
study: effective screen
(not specific)
- prolonged PFA closure
time (suggestive of
platelet defect)

- Factor replacement:IX
- increased risk of
thrombosis after factor IX
infusion
- DDAVP not useful
- steroids!!!
- treatment to eradicate
the inhibitor
- if inhibitor is low give
FVIII
- if inhibitor is high give
FVIIa
- ddAVP: synthetic
vasopressin increased
release of pre-formed
VWF
- aminocaproic acid:
inhibits fibrinolysis
- replace with VWF:FVIII

- rare ie. 1:1,000,000

- most common bleeding


disorder
- vWF synthesized in
endothelial cells &
megakaryocytes
- 3 sub types

- platelet aggregation:
abnormal or diminished
(opposite result for VWF
or Bernard-soulier

- giant platelets
- mild thrombocytopenia
- prolonged bleeding time

Not compiled by Drew Murphy

Hematology
Thrombopathy:
Acquired

Reactive
Thrombocytosis

Prothrombin
20210A
Mutation
AntiPhospholipid
Syndrome

Pregnancy
Oral
Contraceptive
Therapy

Drugs: ASA, NSAIDS,


cephalosporins
Alcohol >BT, >PT,PTT also
prolonged in end-stage
liver dz
- sepsis, bacterial
infections, autoimmune
dz,
- severe iron deficiency
- malignancies

- high lv of abnormal
proteins in peripheral
blood = dysproteinemia or
MM

- prothrombin
- hyper-coaguability
- smoking, birth/control
pills/HRT

- 2 fold increased risk of


DVT/PE
- 3% o population

- DNA test = difinitive

- auto-antibody that
interferes with the natural
anti-coagulant system

- recurrent arterial or
venous thromboses
- 2nd trimester
miscarriages
- thrombocytopenia
- valvular heart disease
- limb asymmetry
- livedo reticularis = net
like rash

- confirmatory tests
required

- increased risk of
thrombosis
- lvs of vWF
- lvs of FVIII
- lvs of Protein S
- compression of gravid
uterus on pelvic veins
- like pregnancy
- clotting factors:
fibrinogen, FII, FVII, FVIII,
FX
- decreased
anticoagulants: protein
C and S
- related to the estrogen

- elevated platelet count


secondary to underlying
disease stses
- platelet count: typically<
1million
- thrombosis is
uncommon
- increased prothrombin
lvs

- prolonged aPTT
- in vitro effect of the
antibody on the aPTT
- mixing study fails to
normalize

Fibrinolysis/Anticoagulant
Disorder

- treatment w/warfarin
indefinitely

- Fibrinolysis/
Anticoagulant Disorder

Fibrinolysis/Anticoagulant
Disorder

- risk factors: smoking,


obesity, DMII, congenital
thrombophilia

Fibrinolysis/Anticoagulant
Disorder

Not compiled by Drew Murphy

Hematology

Disseminated
Intravascular
Coagulation
(DIC)
Trousseaus
Syndrome

Factor V
Leiden
Mutation
Protein C &
S
deficiency
Antithrombin
III deficiency

- always associated w/an


underlying serious illness
- primary lesion: clot
formation
- clinical endpoint:
consumptive
coagulopathy
- bleeding/thrombosis coexist
Causes: gram neg sepsis,
burns, cancer, obstetric
complications, head
trauma, snake bit,
vasculitis
- subacute DIC
- cancer pts
- recurrent superificial
DVTs
- Hereditary resistance to
action of activated protein
C
- aka Activated Protein C
resistance

- excessive/uncontrolled
thrombosis bleeding
- Plasma serum
- organ dysfunction
- bleeding
- shock
- death

- thrombotic
manifestations: acral
ischemia
- Signs of hemorrhage:
mucous membranes, IV
sites, catheters, ETT,
venipuncture sites

- CBC: white cells up or


down with toxi
granulations
- anemia,
thrombocytopenia
- schistocytes
PT /aPTT= prolonged
- II, V, VII, VIII, IX X all ed
- coag test: fibrinogen FI

- antithrombin
- D-dimer
- Fibrin Split products
- fibrinogen = low
Low platelet count
- low D-dimer

- most common disorder


DVT/PE
- aggravated by surgery,
pregnancy, oral estrogen,
inactivity, smoking

- PCR testing

PTT = shortened (donsnt


correct w/addition of
APC)

- C and S are
anticoagulants
- both are Vit K dependent
(liver)
- Impt to prevent
thrombosis

- allows unopposed
conversion of fibrinogen
to fibrin

- treat underlying
disease!!!
- blood products:
platelets, blood,
fibrinogen

- homozygous = death
- heterozygous asymptomatic to
recurrent venous
thrombosis
- Prot. C deficiency
associated with warfarin
hypersensitivity rxn
- spontaneous venous
thrombosis
- homozygous = death
- heterozygous =
asymptomatic until
pregnancy, liver dz,
nephrotic syndrome, DIC

Not compiled by Drew Murphy

Hematology
Lupus
Anticoagulant/Anti
phopholipid
Syndrome

- circulating IgG or IgM

Increased risk of
thrombosis
- recurrent/spontaneous
abortions

- prolonged PTT

Not compiled by Drew Murphy

Hematology

Not compiled by Drew Murphy