Documente Academic
Documente Profesional
Documente Cultură
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
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
Alpha
Thalassemia
Hemoglobin
H Disease
Hg is unstable chronic
hemolytic anemia
Varying severity
Pallor, splenomegaly
- transfusion support
- splenectomy
- Hematopoietic stem cell
transplant
- iron chelation
-splenectomy may be
helpful
- folic acid
- avoid medicinal iron and
oxidative drugs (sulfa
Hematology
Alpha-Thal
Trait
Beta
Thalassemia
Homozygous B0
= Thalassemia
major or
Cooleys anemia
Mild anemia
Nearly normal
erythropoiesis
Normal life expectancy
Normal clinically
Ethnicity: Mediterranean
(Italian, Greek), less often
Asian or African origin
-varying degree of anemia
Homozygous B+ =
Thalassemia
intermedia
Heterozygous B0 or
B+ = Thalassemia
minor
-mild anemia
-no PE abnormalities
-no bony abnormalities
-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
-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
-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
-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
Hematology
Include serum iron, TIBC,
RDW, serum ferritin
Iron Study
Iron Store
Depletion
normal morphology
Iron-Deficient
Erythropoiesis
No morphologic changes
IronDeficiency
Anemia
Anemia of
Chronic
Disease
-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
Hematology
Sideroblastic
Anemia
Vitamin
B12
Deficiency
Pernicious
Anemia
Folic Acid
Deficiency
-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
- 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
-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
B12 deficiency
-malnourished
appearance
- diarrhea
- cheilosis
- glossitis
- NO neurologic
symptoms
Hematology
- malabsorption = GI
diseases, drugs
(phenytoin, sulfa)
- Impaired metabolism =
alcohol, methatrexate
Pure Red
Cell Aplasia
Aplastic
Anemia
-symptoms associated
with anemia which is
often severe
-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
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
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
- hemoglobin normal or
-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
-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
- no specific tx
- avoid oxidative stressors
- splenectomy for severe
cases
- transfusions prn (rarely
needed)
- inform all providers of
condition
-Resistance to malaria
-fava beans = trigger
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
- normal clinically
- risk of renal disease
- 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
- genetic counseling
- no treatment necessary
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 = Schistocytes =
RBC fragments due to
mechanical injury to RBCs
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
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
- often asymptomatic
- onset after age 50
- fatigue
- arthralgias
- hepatomegaly
- skin pigmentation
(bronze)
- cardiomegaly (+/-)
failure
- diabetes
- impotence
-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
LFT = high
- serum iron = high
- serum ferritin = high
(women may be normal)
- test for C282Y mutation
Hematology
Hemosiderosis
Neutropenia
Myeloproliferative
Disorders
Polycythemia
Vera
- common in pts
w/thalassemia
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)
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
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
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
-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
- 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
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
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
- 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
Hematology
- disease of leukocytes
and their precursors
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
- 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
-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
Hematology
3. Blast (immature cells
rapidly proliferat)
- lymphadenopathy
- Mucocutaneous
bleeding/petechiae
- gripping splenic
infarction
-bone pain (blast phase)
- funduscopic:
papilledema, venous
obstruction, etc
- 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
- clonal malignancy of B
lymphocytes
- hypogammaglobulinemia
- 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
- 2% of leukemia
- commonly in whites
- middle age onset
- chemotherapy
- monoclonal antibodies
- alpha interferon
-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
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
- Lactate dehydrogenase
(LDH) = high
-peripheral blood may be
normal
- some leukemic phase
- serum LDH
- monoclonal antibody
(rituximab, CD20 antigen)
- chemotherapy
- watchful waiting
- BMT
- 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
- 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
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
Dx of exclusion
- 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
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
- 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
- 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
- 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
- supportive
- plasma exchange =
plasmapheresis
- symptomatic &
supportive
- antibiotics, BP control,
dialysis/transplant
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
Deficiencies in
HMWK, PK,
and FXII
FXI
deficiency
FVIII, FIX
Deficiency
Hemophilia
A
- prolonged PT
Distinguish b/w liver dz
and vit K deficiency:
- low lvs of 2, 7, 9, 10
- 5 is normal
- NO associated bleeding
- 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
- prolonged aPTT
- FVIII/FIX lvs decreased
- prolonged PTT
- low FVIII lvs
- Factor replacement
Hematology
Hemophilia
B
Inhibitor to
FVIII
- Christmas Dz
- x-linked recessive, only
in males
Provoked spontaneous
bleeding
- limited to
mucocutaneous bleeding
- bruising hx
- increased bleeding after
minor procedures
- hysterectomy for
bleeding
- menorrhagia
Von
Willebrand
Disease
Glanzmanns
Thrombasthenia
BernardSoulier
Syndrome
Prolonged aPTT
- FVIII lvs
- doesnt correct w/mixing
study
- 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
- platelet aggregation:
abnormal or diminished
(opposite result for VWF
or Bernard-soulier
- giant platelets
- mild thrombocytopenia
- prolonged bleeding time
Hematology
Thrombopathy:
Acquired
Reactive
Thrombocytosis
Prothrombin
20210A
Mutation
AntiPhospholipid
Syndrome
Pregnancy
Oral
Contraceptive
Therapy
- high lv of abnormal
proteins in peripheral
blood = dysproteinemia or
MM
- prothrombin
- hyper-coaguability
- smoking, birth/control
pills/HRT
- 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
- 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
Fibrinolysis/Anticoagulant
Disorder
Hematology
Disseminated
Intravascular
Coagulation
(DIC)
Trousseaus
Syndrome
Factor V
Leiden
Mutation
Protein C &
S
deficiency
Antithrombin
III deficiency
- 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
- antithrombin
- D-dimer
- Fibrin Split products
- fibrinogen = low
Low platelet count
- low D-dimer
- PCR testing
- 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
Hematology
Lupus
Anticoagulant/Anti
phopholipid
Syndrome
Increased risk of
thrombosis
- recurrent/spontaneous
abortions
- prolonged PTT
Hematology