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Hematology Collective

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Acanthocytes
Agglutination
Anaplasma marginale
Anaplasma platys
Anisocytosis
Band neutrophil
Basophil
Basophilic stippling
Codocytes (Target Cells)
Dacryocyte (Tear drop cell)
Decreased M:E Ratio
Echinocytes (Burr Cells)
Eosinophil
Heinz Body
Howell-Jolly Body
Hypersegmented Neutrophil
Hypochromic Red Blood Cells
Increased M:E Ratio
Keratocyte
Lymphocyte
Lymphocyte
Macrophage
Mast Cell
Monocyte
Monocyte
Neutrophil
Nucleated Red Blood Cell (Metarubricyte)
Eliptocytes
Plasma Cell
Platelets
Polychromatophilic Red Blood Cell
Reactive Lymphocyte
Reactive Monocyte
Reticulocyte (Aggregate)
Rouleaux
Schistocyte
Spherocyte
Thrombocytes
Toxic Neutrophil
polychromasia
What anemia is polychromasia seen in?
Regenerative anemia
Reticulocyte
What is the dark blue spots called on a reicutocyte?
RNA
Nucleated red blood cell
Howell-Jolly bodies
Hypochromasia
Spherocytes
basophilic stippling
what disease causes basophilic stippling
lead poison
agglutination
neutrophil
rouleaux
what species has rouleaux
horse
echinocytes
why are echinocytes seen on blood smear
slide preparation
poikilocytosis
acanthocytes
keratocytes
hypochromasia
codocytes
another name for codocytes
target cell
What disease is seen with hypochromasia?
anemia
dacryocyte (tear drop)
drepanocyte (sickle cell)
another name for drepanocyte
sickle cell
eliptocyte
another name for eliptocyte
ovalocyte
stomatocyte
schistocyte
monocyte
basophil
lymphocyte
band neutrophil
eosinophil
myeloblast
myelocyte
metamyelocyte
anisocytosis
What is the timeline for hematopoiesis in fetal development?
months:
1-2: yolk sac
3-7: liver major, 3-6: spleen minor
7-birth and beyond: bone marrow
How does adult marrow differ from older adult marrow?
adult: 50:50 (adipose:cellular)
elderly: 70:30 (adipose: cellular)
What are some of the characteristics of bone marrow tissue?
soft, spongy, very vascular, rich in blood supply
RES endotheial cells provide stucture to marrow
What molecules are involved in controlling differentiation of hematopoiesis cells?
cytokines- chemical signals( are synergistic, lineage specific)
growth factors- hormones- c-kit kigand causes further stem cell proliferation
receptors- binding sites for chemical signals- cell surface(bind cytokines and growth factors)
What are some characteristics of stem cells?
morphology resembles a lymphocytes
high nuclear:cytoplasm ratio
light blue cytoplasm
purple, open nucleus
What is the composition of blood?
fluid portion- plasma- 55%
serum plasma- clotting factors

cellular components- RBC's mass measurment Hct-45%
WBC and platelets- buffy coat
What are the characteristics of RBC's
biconcave disc, anucleated, 6-8 microns, contain Hgb
Characteristics of platelets
not true cells, cytoplasmic fragments produced it the bone marrow. help keep vascular system in tact
hematology specimens(EDTA, WB, citrated plasma,) and capillary specimen
EDTA,WB- CBC, H&H, indices, RBCM, differential, reticulocyte count, platelet count
EDTA, WB, citrated plasma- ESR(no capillary specimen)
citrated plasma- protime, aPTT, factor assay
Why cant we use heparin or Na citrate for specimen collection?
heparin- distorts morphology, clumps plasma
Na citrate- causes dilutional error
how quickly should one perform a blood smear? when is it unacceptable?
within 2 hours of draw. unacceptable after 4 hours
What are the solutions involved in a Wright stain?
polychrom methylene blue
eosin
methanol(fixer)
potassium and sodium phosphate buffers
What does the ideal pH on a wright stain look like?-generally
stains cellular detail with good resolution. cell borders are distinct. chromatin patterns are apparent.
What is the optimum cellular color?
RBC's- mauve or salmon. free from artifacts
too acidic ph looks like?
nuclear characteristics are pale blue
cytoplsams looks gray instead of blue
RBC's appear bright red/orange
eosinophils granules are brilliant red-orange
lact cellular contrast
causes of acidic pH?
stain time too short. extended buffer time. excess washing. old stain
too alkaline pH look like?
nuclear details appear deep dark purple blue with little ocntrast in chromatin patterns. neutorphil granules appear large and toxic. RBC are blue-green. eosinophils granules are blue-gray. lymphocytes cytoplasm is gray-lavender
causes of akaline pH?
smear too thick, extended staining time, insufficient washing, fresh stain, not aged
What is rouleax, agglutination?
roulaux- coin like stacking
agglutination- clustering due to antigen interaction
What do you look for in a 10x scan?
overall stain quality, WBC estimate(counted/fields)(200cells/microliter)
what do you look for in a 100x scan?
differential (100 WBC's), RBC size shape color(too much color= increased Hg), platelet estimate (counted/fields)(15,000)
absolute count
calculation of absolute cell numbers based on percentage of type multiplied by the total cell count.
characteristics of banded neutrophil?
less mature than segmented, often seen under stress. released early from bone marrow bc of stress
characteristics of segmented neutrophil?
10-14 microns, pink to tan 2-5 lobed nucleus, coarse, dense chromatins, fine granules
47-80%
characteristics of lymphocytes?
7-10 microns resting, 12-16 micros stimulated. clear to medium blue cytoplasm. dark, dense chromatins.
relative 13-40%
kids have elevated lymphocytes(4000-10500microliter
characteristics of monocytes
12-18 microns (largest). abundant gray blue cytoplasm with ground glass granules. lacy chromatin. phagocytic with prominent vacuoles (not differential)2-11%
characteristics of eosinophils
large red/orange granules contain antihistamines. increased are found with parasitic infections and allergic reactions. 0-3%
characteristics of Basophils
dense, segmented nucleus. large, coarse, blue black granules. granules contain heperain, histamine
0-2%
platelet satellitism
platelets are functionally potent and react iwth a variety of protein receptor and negatively charged surfaces, such as glass, collagin, basement membrane
hematocrits and ESR both rely on what? Microhemtocrit vs. macrohematocrit volume?
Red cell mass.
micro- <0.1ml capillary collection is acceptable
macro- 1.0 ml= ESR. capillary collection unacceptable
hematocrit- measures, expressed as?
hematocrit is a direct measure of red cell mass and an indirect measurement of oxygen carrying potential. is expressed as L/L or %
What effects Hct?
Hct is eveluated to assess anemia(low volume of packed red cells/whole blood volume)
-acute/chronic loss of RBC
-inability to make RBC
Clinical values of Hct?
decide on transfusion= <30%. critical call <18%
evaluates renal function which produces erythropoetic which signals marrow RBC production

monitors dehydration- Hct is elevated due to loss of tissue fluid
sources of error-MCV automated calculation
hyperglycemia- cell swells(increased glucose)
hypernatremia- (increased sodium)
WBC>35,000
What is a improper Hct specimen?
short draw has dilutional effects with liquid anticoagulants
use of herparin(creanates RBC)
IV fluid may dilute sample. tissue fluid alters depending upon time of day
hydration/iv status
hemolysis
What are some adaptations to anemia?
increases hct: high altitude, smokers, newborns
decreased: pregnancy
ESR- macrohematocrit test. priciple of test
erythrocyte sedimentation rate. rate at which cellular elemetns setlle out of whole blood sample. measured in mm/min. distance in 60 min

RBC's have a negative charge and naturally repel each other bc of zeta potential. asymmetric plasma proteins decreases negative charge and decrease zeta potential, cells rouleaux
What are the phases of ESR
10 min of rouleaux formation
40 min of sedimentation phase
10 min of packing phase
some disorders affecting ESR
increase: acute systemetic infection. neoplastic disease. leukemia, multiple myeloma

decreased: sickle cell, HbC disease, HbS disease, polycythemia vera
factors affecting ESR
acute phase reactant- hyperfibrinogenemia(increases)
-tissue necrosis, infection, pregnancy

haptoblobin(increases)
-chronic infection, maglignancy
technical factors effecting ESR
tube length, tilt, temp, timing of test, surface vibrations, bubbles
three methods of ESR testing
westergren, wintrobe, mini- VES
what are the functions of hemoglobin
transfer o2, transfer co2, buffer blood.
hct=3xHgb. 1/3 of RBC volume and 90% of weight=Hgb
what is hemoglobins stucture
Hb is a fluic protein that transports gases. tetramere with 4 globin units. two dimer protein pairs. oxygen attaches to a heme unit(2 alpha and 2 beta chains) must be in 2+ oxidation states

folding of globin units creates a hydrophobic pocket for the heme unit
What kind of Hb dimers are formed for a globin chain?
a2b2, a2g2, a2sigma2
What is the fetal hemoglobin? Where is it produced and what is its affinity for oxygen?
a2gamma2 predominant Hb in fetus. produced in lilver ad spleen. HbF has a higher affinity for o2 than HbA1
What is the adult hemoglobin?
HvA1(alpha2beta2)- predominant hgemoglobin of adults. beta chain synthesis does not exceed gamma chain synthesis until after birth. following birth, HbA will increae fo rthe next 12 months and HbF will be made in small amounts
What is the alternate hemoglobin?
HbA2 (alpha2 sigma 2) occurs late in fetal life. delta chain production begins 7.5-8 months gestation. 2.5% normally found post birth
What are the proportions of Hb at birth? In adulthood?
at birth- HbF-70% HbA1-30%
adult: AbF-1%. HbA1-97%. HbA2-2.5%
What are some important steps in globin synthesis?
cells must have DNA. 65% of hemoglobinization is complete while thenucleus is intact
35% of Hb is assembed after nucleus is extruded
assembly of chain occurs attached to ribosome.
What are some important steps in heme synthesis?
Heme is porphyrin ring + ferrous iron
synthesis of heme occurs between the mitochondria nd cytoplasm of the red cell
goes to cytoplasm when heme unit is complete and combines with globin chain
What are the steps of heme synthesis?
Delta-aminolevulinic aci is the rate limiting step
What is a normal hemoglobin value? Units?
13-17 g/dl males
12-15 g/dl females
anemia= Hb<10 g/dL
What is a critical call for Hb?
<6.6 g/dL
>19.9g/dL
What conditions increase red cell needs for Hb?
high altitude, emphysema, cigarette smokers, long distance runners, pregnancy(appears to benet decrase bc plasma volume increases greatly)
What are some adaptations to anemia?
immedite response:increase HR, respiration, circulation
What is the molecule that causes O2 to be released more readily?
2,3 diphosphoglycerate
Factors that shift Hb curve right?
dec pH, dec pO2, inc temp, inc pCO2, in 2,3 DPG
Excess H+ is bound to what?
deoxyhemogloin
What is the Bohr effect and chloride shift
chloride shift accounts for 70% of CO2 transpotation to lungs.
25% of CO2 is directly bound to Hb and transported
5% is dissolved in the plasma
How is Hb measured? How is the test completed?
Whole blood is added to modified Drabkin's reagent. The red cells are lysed: Hb is released. All Hb is converted to the ferric state Fe+3 of metHb. MetHb is converted to cyanmethemoglobin by KCN. Absorbance measured at 540nm.
RUN IN DUPLICATE
What is Drabkin's reagent chemical name?
potassium ferricyanid (K3Fe(CN)6
What is carboxyhemoglobin and what are some symptoms?
CO bound to heme. lips and nails have a cherry red color. CO: heme binding is 200% stronger than 2
acute carboxyhemoglobinemia=death
smkers ahve increased CO level
What is extravascular degradation and what are the important steps?
Histiocyte reticular endothelial cells phagocytize red cells.
What is the clinical utility of MCV, MCH, MCHC?
indices help categorize enemias- abnormal morphology can be calssic for a disease state
indicate iron storage levels.
monitor transfusion therapy- MCV is patient specific
What is the MCV equation and reference range?
MCV=Hctx10/RBC
normocytic= 80-100 fL
microcytic= <80fL
macrocytic= >100fL
Macrocytosis= associated with what disease?
Young blood cells- diffusely basophylic erythrocytes.
newborns, pos surgical, post partum, pregnancy, iron replacement therapy, hemolytic anemia, hemolytic deficiency fetal/newborn

B1 deficiency, alcholism, liver disease, chemotherapy
Microcytosis= associated with what disease?
Iron deficiency, Thalassemia(genetic disorder), decreased iron utilization, RBC fragmentation
MCH equation and reference range?
MCH= Hbx10/RBC (picograms)
26-34 pg reference range
not sex dependent, related to Hb within red cells.
"times 3" rule for QA Hbx3=HCT
RBCx3=Hb
MCHC equation and reference range?
MCHC=Hbx100/Hct (grams/dL) (%)
indicates color of red cells
normal 32-36%
hypochormic <32%
hyperchormic >36%
RDW(red cell distribution width) equation and reference range?
RDW=SDx100/MCV (%)
reference range: 11.5-14.5%
RDW>16 indicaes anisocytosis- cell population with lots of variation. Individual size difference of red cells
Diffusely basophillic erythrocytes
immature REC, not fuly hemoglobinized and carries less O2. Bluish color
Severe anemia shows what?
Nucleated red blood cells- if bonemarrow is responding to anemia/blood loss
What is anisocytosis, microcytosis, macrocytosis?
anisocytosis= increased cell size variation
microcytosis- decreased red cell volume
macrocytosis- increased red cell volume
What is a echinocytes?
dueto changes in the lipid bilayer. evenly distributed pointy projections; crenated
results from : increased pH, septicemia, renal insufficency, artifactual
Stomatcytes?
Mouth cells
uniconcave cells; incresed cell membrane/surface area.
resuts from alcoholism, liver disease
Spherocytes
membrane abnormalities genetic or acquired
cells appear as densely staining balls. No area of central pallor
MHCH>36%-only reason
Schistocytes
Fibrin strands, severe burns, mechanical heart valves, glomerular nephritis
Acanthocytes
thorn like spines- irregular bulbous projections
results from chages in plasma lipids, alcoholic cirrhosis, lipid metabolism disorder.
codocytes
bull's eye, results from increased cholesterol and lipids

increased surfaceara to volume ratio
skin to big for volume of cell
Dacryocytes
inclusion removed by spleen. Myelodysplastic syndromes (MDS) TEAR DROPS
Depanocytes
sickle cells- genetic abnormality results in HbS formation. deoxygenated cells sickle
Na+ metabisulfite
What are HbS EM?
spiney fingerlike projections that are reversible with reoxygenation of RBC's
Elliptocytes
hereditary membrand abnormality. can also be aquired or artifactual
Keratocytes
Helmet cells- horn like projections results from spleen removing large inclusions
aka blister cells
cells are caught upon intravascular fibrin strands
HbC crystals
genetic abnormality. HbC becomes crystallized
Basoillic stippling
RNA- found in Pb poisoning
"blue berry bagel"
Howell Jolly Bodies
DNA- single densly staining dots. never more than one per cell
dyserythropoiesis-spleen removed
Cabot Ring
mitotic spindles found in dyserythropoiesis
Heinz bodies
Denatured Hb
round refractive- not visualized w/ wright stain- supervital stain
purpleish staining inclusions. multiple per cell
Pappenheimer Bodies
iron deposits in severe anemia
looks lke basophillic stipling
aka siderotic granules
wright stain/prussion blue stain
Infectous Organism-
malaria and babesia
Cold agglutinins
extremly common. MCHC>36%, falsely low RBC count. warm it up if seen on slide first.
Rouleaux
coin like stacking of RBC. results from inc plasma protein. found in multiple myeloma
List of myeloproliferative diseases
-Polycythemia rubivera
-CML
-Agnogenic Myeloid Metaplasia
-Essential thrombocythemia
-Myelodysplastic syndrome

Note that leukemias are normocytic
Tx for polycythemia rubivera
-Phlebotomy to remove RBCs and lower viscosity and make patient iron deficient to slow RBC production

note polycythemia rubivera is an inappropriate response cuz the oxygen tension is normal in one's body
Sx of polycythemia rubivera
The 4 Hs
-Hypervolemia
-Histaminemia
-Hyperuricemia
-Hyperviscosity

Hypervolemia: the plasma for some reason matches the rbc production for some reason
Histaminemia: clx itchy, causes VD -> Headaches
Hyperuricemia: Hematopoesis is up -> recycling of purines -> uric acid. This extra uric acid can bust the kidneys up and this is called Tumor lysis syndrome. Tx w/allopurinol
What are the levels of rbc mass, plasma volume, oxygen saturation, and erythropoetin like for poly rubivera and for high altitude/COPD
Poly Rubivera
-RBC mass is up
-Volume is up
-Oxygen sat is normal
-erythropoietin is down.....this hormone response to low oxygen tension

In high altitude or COPD
-RBC mass is up
-Volume is normal
-Oxygen sat is down
-Erythropoietin is up
Describe Leukemia
-Normocytic anemia
-always causes anemia
-usually low platelets
-usually high WBCs
-metastases usually to lymph nodes and spleen
-Blasts in blood
-Acute vs chronic leukemia: do a blast count in the bone marrow if less than 30% are blast it's chronic

-
Type of leukemia age brackets
0-14: ALL
15-39: AML w/Auer Rods and acute myeloblasts
40-59: AML, CML pick one w/a blast count or philly chromosome in CML
60 or more: is CLL
CLL is the most common regardless of age
Most common cause of someone over 60 w/non-tender swollen lymph nodes is CLL-these are metastases to lymph nodes
The 2 tests for CML
1. Leukocyte Alkaline Phosphatase stain. Neoplastic CLL cells don't have this. CML has a low LAP score
2. Identification of the philly chromosome
What is extramedullary hematopoesis
Hematopoesis outside of the bone marrow
What is Agnogenic Myeloid Metaplasia
Occurs in myeloid proliferative disorders.
-All hematopoetic cells move to the spleen and a couple stay behind. Megakaryocytes that stayed behind start laying down collagen -> fibrosis. Cells that remain have to get out of the cords that are not all thick and they get sheared -> tear drop cells
What kinds of Antibodies do you make in chronic lymphoblastic leukemia?
NONE
These are undifferentiated blasts thus they can't get to plasma cells
What is the marker for Acute lymphoblastic leukemia
CD10 on B cells
How do you test for Hairy T Cell Leukemia
TRAP stain
tartrate resistant acid phosphatase
Which cancer likes to invade gums
AML
What are the 3 main features of acute progranulocytic leukemia
-Translocation of chromosome 15-17
-DIC
-Retinoicacid is the treatment as it causes the undifferentiated cells to progress.
What are the highlights of CML
-Neutrophilia in PBS
-Thrombocytosis in PBS
-Philly Chromosome leads to a tyrosine kinase being on in pluripotent HSCs.
-Shortened chromosome 22
-Bone Marrow Hyperplasia
-Sx: fatigue, weightloss, early satiety, leukostasis, urticartia from too many basophils
-Mild anemia*: even tho it's a myeloproliferative disease! ->pallor
-Splenomegaly
-Arthritus from uric acid deposits
-In PBS you see all stages of cell differentiation
-hypersegmented neutros
-Completely environmental and there's no hereditary component
-Age onset is 50s
What can too many neutrophils do in CML
-Sx of dyspnea, slurred speech, blurry vision, confusion.
-Priapism, hemorrhage all due to sludging of leukocytes

neutrophils are sticky and cause these sx
In CML what is the leukocyte alkaline phosphatase like and B12 level
The leukocyte alkaline phosphatase is some stuff only in normal neutrophils and since these are malignant ....
-B12 is increased but no one knows why
What is the blast crisis?
Its in CML where there's less differentiation all of the sudden and it starts looking like leukemia and sx get worse.
-Possible extramedullary hematopoeisis.
What are the tx for CML
Interferon-no one knows how it works
-BM transplant
-Imatinib (gleevac): targets the tyrosine kinase of the Bcr-Abl protein
Describe Polycythemia Vera
-This is the erythrocytosis disorder
-"Increased RBC mass, not count"
-Vertigo, visual probs, fuzzy, early satiety all due to higher blood viscosity
-Onsets 50-60s y/os
-Pruritis regardless of hot or cold shower
-Sx are similar to budd chiari of abd pain, ascites, and HSM
-Dx it by elevated RBC and Hct w/o any secondary cause ie low oxygen tension or COPD. Ex if erythropoeitin is low and ur Hct is super high
-Neutrophilia and thrombocytosis
-Iron deficiency* but no anemia
-Marrow is hypercellular w/inc megakaryos and no iron can be seen.
Labs for Polycythemia Vera
-Normal O2 sat
-Hyperuricemia
-Decreased erythro
-Elevated B12

Fakers of the disease would be cardiopulmonary disease and kidneys make more erthryo, high altitude, CO poisoning.

Tx for P vera is phlebotomy and allopurinol
Decribe Essential Thrombocytopenia
-target age is 50-70
-Erthromelalgia where BVs get blocked and inflamed -> seen as burning soles and palms
-Thrombosis
-Leukocytosis and marrow fibrosis
-NO! splenomegaly
Labs:
increased Hct, RBC mass, plasma volume
Microcytosis, neutrophilia, basophilia
-Marrow hypercellular w/iron completely absent

Tx: anagrelide-prevents budding of platelets off megakaryocytes
Describe myelofibrosis
which is another myeloproliferative disease
-Leukocytosis, thrombocytosis, and anemia
-May go into a blast phase in 5-10 yrs
-Death by an enlarged spleen
Myelodysplastic syndromes
-ineffective blood cell production
-May progress to leukemia
-These are busted hematopoeisis disorders that have a tendency to go toward AML
-Hypoproliferative macrocytic anemia is present
-BM is hypercellular
Test: in CML what are the labs like for
WBC, RBC, Plt, LAP score
Spleen
WBC up
RBC slight down
Platelets up
LAP down
Spleen up

100% of people will go to blast crisis
Test: in CML what are the labs like for WBC, RBC, Plt, LAP score, Spleen
WBC up
RBC up
Plt up
LAP score up
Spleen is regular

Some go to blast crisis
Test: In essential thrombosis
What is the WBC,RBC,Plt,LAP score, Spleen
WBC up
RBC regular
Plt Up
LAP reg or slight up
Spleen regular

Doesn't progress
Test: In MyeloFibrosis
Whats the WBC,RBC, Plt, LAP score, spleen
WBC up
RBCs down
Plt up
LAP normal
Spleen up

Less than 20% go to blast crisis
In myelodysplastic syndromes
Whats the WBC, RBC, Plt, LAP, and spleen like
WBC Down
RBC Down
Plt Down
LAP Down
Spleen Up
Sx of acute leukemia
Sx are due to failed hematopoeisis
-fever, weakness, bleeding
-pallow, petechiae, HSM
Types of Leukemia
1. ALL
2. Acute myelogenous leukemia
Difference between AML and CML
In AML all the symptoms and effects are quick
-The BM is non-differentiated, it just blasts
-Other cells are quickly pushed aside in the marrow causing a decrease in RBCs, platelets
-You see oral lesions because there's no differentiated cells at all ie no neutrophils and thus mucus membranes ->oral lesions

AML sx
-bleeding
-Adenopathy
-Splenomeg
-Lekostasis
Sx of AML
Adenoids
-Pancytopeia comes on quick cuz there's no differentiation
Oral/rectal lesions
-Lactose Dehydrogenase is increased
-Associated w/Bloom and Fanconi syndrome which mess w/chromosomes
-Hb down
-bleeding from gums
-Gums hypertropy
-Ecchymoses
-Congestive Heart failure
-DIC
-15:17 translocation
-Kidney failure due to extra uric extra depositing in the kidney
AML bone marrow
BM is all blasts and no differentiation at all
-Huge nuclei, little cytoplasm = blast
-Not shown well in this pic but Auer rods are dx of AML

There are many different kinds of AML and they differ by the amount of granules in the cytoplasm of the blast cell. The pic shown here has no granules and makes it less curable cuz there's multiple chromosome abnormalities in these
Types w/granules are usually due to a 15:17 translocation and are curable
Other possible chromosomal changes that might lead to AML
Missing a chromosome 5 or 7
Trisomy of 8
Missing chromo Y in a cell
trisomy of 4

There's many different chromosomal abnormalities for the many types of AML. 2 are a translocation between chromosome 8 and 21 another type is translocation between 15:17

The translocation 8:21 and 15:17 are highly curable while ones like 9:22 are not favorable
Describe Acute Promyelocytic Leukemia
-sub type of AML
-DIC-hemorrhaging is their main sx to come in to the doctor
-Azurophilic granules-auer rods
-t(15:17) or (11:17)
-death form intracranial hemorrhage
-This cancer type can be forced to differentiation by retinoic acid
-This means that this subtype is highly curable
-Also u can tx the sticky neutrophils with steriods which makes them unsticky.
-This is the only cancer where u can do differentiation therapy....not prostate or breast cancer
-APL translocated a retinoic acid receptor gene when it did the 15:17 and this makes it different from regular AML
Factors for poor survival and remission of AML
-Bad risks
-elderly
-prior radiation
-transloc of 5 and 7 or mutations of those chromosomes
-male gender
-APL is usually in younger people
-hx of preleukemia
-higher white count

all lead to poor survival
Avg survival of AML
2 years and peeps die of pancytopenia and infection
Describe ALL
-Cancer of immature B cell that can occur at the bone marrow stage or any stage in between becoming a plasma cell at a lymph node
-If in BM it'll push aside everything else so no platelets or neutrophils
-Usually a cancer of pre-B cell
-CD 10 is the marker for this
-Tdt + and CALLA+ which is common ALL antigen, CD10+
-A bunch of huge B lymphoblasts indicating that they're precursors
Subtypes of ALL
-Childhood type called L1
-Adult called L2
-Burkitt's lymphoma called L3 (transloc of 8:14)

The adult ALL can have a philly chromosome
-ALL is PAS+ which is positive cytoplasmic granules (lymphenate) in blasts
Tx of ALL
-corticosteroids ->WBC apoptosis,
-anthracycline antibiotics
-BM transplant
Most B cell lymphomas occur during/after class switching
-CLL is before the lymph node
-Hodgkins come from a broken germinal center
-Multiple myeloma is a plasma cell
-A memory B cell is burkitt's lymphoma and malt lymphomas
Describes Hodgekin Lymphoma
-Starts in a single node and moves contiguous orderly, node to node
-Has RS cells
How to tell if a blast is from ALL or AML
AML stains w/peroxidase and Sudan Black B stain
Sudan B will stain myeloblasts but not lymphoblasts
Also no Auer rod in ALL, But AML doesn't ALWAYS have Auer rods
-ALL is TDT+, CALLA+, and CD10 a pre-B cell marker.
Tdt is used in B and T lymphocytes
Acute promyelocytic Leukemia
-Azurophilac granules
-DIC
-Translocation 15:17 or 11:17
-PML-RAR alpha
-Tx retinoic acid
-Distinct feature of APL is DIC caused by granules that activate thrombn and factor 10 and 2
Lymphoma vs myeloma
-Lymphoma tend to occur at immature B at a node or pre-B in BM
-Myeloma occurs in a plasma cell
Describe Hodgekin's Lymphoma
-Starts in a single node and can spread to adjacent ones
-Has a double incidence where its high in kids and elderly unlike NHDG where risk goes up w/age.
-Slow progressive disease
-Malignant cells are a small % of the tumor
-First cancer curable w/chemo
-Malignant cells called Reed-Sternberg cells which are large bi-nucleus cells w/prominent nucleoli
-RS cells are transformed B cells
Describe RS Cells
-transformed B cells in a lymphoma
-Lack all B and T cell antigens
-Variable expression of CD20+, but usu always express CD15 and 30+
-bi-loped nuclei and eosinophilac nucleoli call owl's eye
What are the 5 classical Hodgekin Lymphoma Subtypes
-Nodular sclerosis HDG
-Lymphocyte rich classical HDG
-Mixed cellularity HDG
-Lymphocyte Depletion HDG
-Nodular Lymphocyte-predominant HDG

Lymphocyte depleted ones have the worse outcome
Describe Nodular Sclerosis HDG
This one is the the most common
-Nodular w/fibrous bands separate the lymph follicle
-Have lacunar variant cuz there's space around th RS nuclei
-Loss cytoplasm
Describe Lymphocyte rich classical HDG Lymphoma
-RS cells w/bunch of lymphocytes
-Rare or no eosinophils
-Nodular pattern w/no fibrosis
Describe Mixed cellularity Hodgekins
-RS cells w/histiocytes
-lots of eosinophils
-lots of plasma cells
Describe Lymphocyte Depletion HDG lymphoma
-Fibrosis
-Lack of inflammatory cells
-RS cells
Describe Nodular lymphocyte predominant HDG
-Nodular
-distinct type of RS cells w/L&H variants wpopcorn shaped nuke
-CD20+
-This type of HDG doesn't req chemo
Pic of nodular HDG lymphoma
Dense collagen bands separting tumor nodules
Hodgekin Lymphoma Clx presentation
-Painless adenoid in neck or axilla
-fever, night sweats, weight loss, pruritis
-Mediastinal mass where it might be located causing chest pain, dry cough
-Pruritis may occur at tumor site w/consuming alcohol
-HSM
-on ct or xray u see a widening of mediatrinum
"Drink a beer and get itchy"
How to dx hodgekin
-Excisional biopsy ie not needle biopsy so you can see the fibrous bands.
-Increased ESR, LDH are both elevated
-Easy to pick up in PET scan
-Only do a BM if super advanced cuz lymphomas don't start out in the bone marrow
Ann Arbor HDG and NHDG lymphoma staging
stage 1
one lymph node
stage 2
two or more sites on same side of diaphragm
stage 3
both sides of diaphragm
stage 4
more than one organ outside lymphatics
Risk factors for HDG
-Male
-Over 45
-Low Hb under 10
-Super high or low WBCs
-Low albumin
Tx for HDG
ABVD
Adraimycin
Bleomycin
Vinblastine
Dacarbazine (alkylator)

For high risk cases add BEACOPP which includes prednisone

85% cure rate for HDG
Difference between NHDG and HDG
NHDG u die way more
Most of the tumor cells in NHDG are malignant cells unlike HDG
-HDG lymphomas are called that because they have an ordered spread from one lymph node to the next
-HDG lymphomas have RS cells
Describe NHDG Lymphomas
-Lymphocytic lymphomas which are like the lymph node form of CLL
-Burkitts lymphomas
-follicular lymphomas
-mantle lymphomas
-diffuse large cell lymphomas
Describe Burkitt lymphoma
-IgH-Myc translocation
-It is a diffuse large B cell type NHDG lymphoma
-Produced by an 8:14 translocation
-Gives a starry sky appearance in histo: macrophages in the lymph node eating up a bunch of dead cells

Even tho this is a cancer of lymphatics the bone marrow will show blasts with vacuolated cytoplasm and prominent nucleoli
LDH will be very high
The types of NHDG lymphomas
-Follicular lymphomas-Most common adult lymphoma and hits B cells, t(14:18)
-Diffuse large B cell: adults more than kids get it. It is mostly B cell. Usu presents w/extranodal mass.
-Lymphoblastic lymphoma which is the most common child form. Usu presents w/ALL and a mediastinal mass. This is formed of immature T cells
-Burkitt's lymphoma-hits adults and kids and made of B lymphocyte.
-Small lymphocytic lymphoma-hits adults ad isof the B cell type. Can do richter's transformation into diffuse B cell lymphom
A diffuse large b cell lymphoma
A follicular B cell lymphoma
Follicular type is the only B cell lymphoma w/nodules
Aggressive NHDG vs Indolent
Aggressive :
-diffuse large b cell lymphoma
-quick growth, painful
-extranodal sites like lung, kidneys
-acute ilness
-more common than indolent
-CD20+
-Not tx w/surgery cuz grows so quick
60% of it stays in nodes and 40% goes elsewhere
-The more mature the B cells in the lymphoma are the better the tx outcome
-Tx is R-CHOP and stem cells


Indolent
-follicular, small lymhphocytic
-slow growth
-just in lymph nodes
-cytopenia from BM involvement is common
-Tx w/rituximab to CD20
Another type of less common NHDG is Marginal zone lymphoma
-Includes MALT lymphoma
-Indolent type
slow grower
-good prognosis
-CD20+, CD5-,CD10-,CD23-
-Very responsive to rituximab
-Driven byH.Pylori
Another type of NHDG is Small lymphocytic lymphoma
-Sim to CLL (which is known for its smudge cells) but it's in a lymph node
-CD20+, CD5+, CD23+
-Involves nodes, spleen, liver, BM
-Can undergo "Richter's transformation" where the lyphmoma can change into a diffuse B cell lymphoma
-Makes densely packed lymphocytes overcrowding the blood = smudge cells
Another type of NHDG is mantle cell lymphoma
-Involves GI tract
-lyphoid polyposis
-transloc 11:14
NHDG T cell lymphomas
-Super aggressive compared to B
-Diffuse erythroderma
-skin peeling
-Sezary syndrome = diffuse erythroderma. Sezary cells : brain shaped nuclei in lymphocytes
-Most are cutaneous T cell lymphomas
-super itchy, dry skin
NHDG tx
CHOP
Cyclophosphamide
Hydroxydaunomycin
Oncovin
Prednisone
point is not to use overlapping toxicities

Rituximab anti-CD20
True statements about lymphomas
All hodgekin lymphoma and 90% of NHDG are derived fro mB cells
Overall Hodgekin can be cured in 85% of cases
The dx procedure for painless lymph node is excisional biopsy
Rituximab is used only in NHDG
In AML you have leukostasis and low RBCs should you do a red cell transfusion?
no because the high number of leukos causes leukostasis or plugging of capillaries in brain, lungs -> dizziness and SOB and more RBCs->viscosity = fuel for the fire


Don't forget Auer rods distinguish between AML and ALL
Difference Between AML and CML
AML
-px has too many immature granulocytes
Auer Rods
Lysing these white cells, these rods can -> gout
-AML gets the fab classication of like M2 and M3. M2 has natural granulocyte maturation and M3 is very responsive to retinoic acid ie promyelocytic ones
-M2 t(8:21)
-M3 t(15:17)
-M2 and M3 are both favorable

CML
-px has too many differentiated granulocytes
philly chromosome
-Uses bcr-abl inhibitor imatinib

family history means nothing in both
Tx for AML
Induction chemo followed by consolidation chemo to get rid of residual tumor cells
How do you know if a leukemia is in the acute or chronic form
Acute u see nothing but blasts and chronic u see some differentiated cells
acute can kill w/i 3 months cuz all u have are blasts
What is TdT like in lymphoma?
In lymph node cells are atleast immature B cells meaning they are not TdT positive so in lymphomas u see TdT-
Man gets a biopsy of a mediastinal mass and it looks like this
What is this?



Burkitts starry night
many cells of one kind ie macrophages eat dead stuff and they are the white cells in the pic
Clinical case of a women w/a non-healing tongue ulcer who was dx w/leukemia earlier
she has a granulocytic sarcoma or chloroma
-u tx this as leukemia cuz this is an example that leukemia can deposit into tissues
-Subtype of AML most associated with chloromas is M5 which is a monocytic leukemia
-AML M5 is infiltrative
Combination chemotherapy
Adjuvants-give when no longer can see disease or after surgery
Neoadjuvants-give before a surgery
Salvage-first therapy didn't work so try something else, like palliative therapy.
Induction-given to reduce remission
Consolidation-get residual tumor cells
Maintenance-given a long time after remission
Name two diseases or tumors where chemo does nothing
adenocarcinoma and GI adenocarcinomas
Clinical trial stuff
stage 1-seek a tolerable dose
2. What's a max dose
3. how efficacious comared to other
4. in the markt
Drugs for cancer
Alkylating agents-make DNA breaks
Antibiotics-blocks DNA unwinding
Plant alkaloids-Inhib MTs
Camptothecins-Inhib topo 1
Antimetabolites-trick immune system
Hormonal Agents-may cause a cell to mature
Novel Therapies- new stuff like giving retinoic acid
Alkylating agents for cancer
-Nitrogen mustard
-Creates a Carbon+ like an electrophile which binds to nitrogen in DNA bases which causes DNA breaks
-Toxic to ears and kidneys
-They alkylate DNA -> repression
-drug names: cyclophosphamide, mechlorethamine, ifosfamide, busulfan, dacarbazine, procarazine
Antibiotics for cancer
-Binds DNA between base pairs and prevents uncoiling of DNA, this is called inter-chelating
-Also can inhibit topoisomerase 2 which is used in cell development
-Side fx: cardiotoxic, alopecia, myelosuppression.
-drug names: doxorubicin, duanorubicin, bleomycin, procarbozine, dactinomycin
Plant alkaloids for cancer
-Inhibit microtubules
-Includes the drugs vinca alkaloids, taxanes, camptothecins, and epipodophyllotoxins
-Vinca alkaloids are neurotoxic, and from the perrywinkle plant. Side effects are marrow suppression, and they eat up MTs in nerves. Drug names are vincristine and vinblastine

-Taxanes from the yew tree. causes way too many microtubules but has some complex way of stopping them. Drug names are paclitaxel, docetaxel. Adv effects are neuro and arthralgia

Camptothecins: inhib topoisomerase 1-> DNA breakage. Drugs names ironotecan, tpotecan. Side fx are myelosuppression and cholinergic reaction

-Epips inhibit topoisomerase 2. Drug names for Epis are etoposides, teniposides.
Antimetabolites for cancer
-Antimetabolites: like antifolates, substitute for metabolites that are normally put into key molecules. Drug types are methotrexate (inhibs dihydrofolate reductase -> inhibs purine and thymidylate synthesis. Side fx are pulmonary, liver, bone marrow suppression
-Another antimetabolite is 5-FU which is an inhib of thymidylate synthase
-Another antimetabolite is hydroxy urea which does marrow suppression

Note* a second drug class is
-Hormonal agents: Tamoxifen is an anti-estrogen.
-Novel therapies like retinoic acid for APL
Imatinib for CML's Bcr-Abl
Rituximab for non-hodgekin lymphoma. Trastuzumab
A primary polycythemia has a high or low erythropoeitin?
Low
All of the sx of polycythemia vera are due to blood viscosity
This HA, weakness, sweating, gouty arthritus, fingers and toes turn red.
-HSM due to extramedullary hematopoeisis.
-iron deficient -> microcytosis
-No stainable iron
How can polycythemia vera kill you
Thrombosis
transformation to acute leukemia
Myelofibrosis with myeloid metaplasia
Pvera bone marrow biopsy
hyper cellular w/high number of megakaryocytes
no stainable iron either

also note that 95% of peeps w/p vera have a JAK2 mutation
Tx for pvera
ASA
Hydroxyurea
anagrelide
phlebotomy
In CLL what cell markers are there
U have B cells w/CD19, 20, 5. Usually cd5 is on a T cell
When u see these 3 CDs on a b cell it auto means CLL
-This can lead to autoimmune hemolytic anemia
Sx and smear of hairy b cell leukemia
-TRAP stain-shows hairy cell
-"doc i finally dropped this extra weight that i haven't been able to get rid of"
Slide of essental thrombocytopenia
jak2 mutation only occurs in like 50% of these so can't make a dx based on it
Where are the B cells located that have CD19/20,
If B cells have CD19 and 20 they are in the blood

B memory cell cancer is CLL
Plasma cell cancer is Myeloma
Describe myeloma
-Myeloma makes multiple copies of one antibody
-It looks hyperglobulinemia but actually it's hypo cuz u lose diversity of other antibodies due to suppression molecules and u can't fight encapsulated bacteria
-People die by infxn of encap bacteria
Describe myeloma's pathogenesis
After it becomes crazy in the lymph node it infiltrates the bone marrow
-Suppression of platelets, rbcs, other white blood cells ->pancytopenia
-It activates osteoclast activity ->bone lesions
-Causes hypercalcemia and these deposits can hit the kidney
Clinical presentation of myeloma px
-Focal bone pain
-Comes in w/broken arm or leg
-High levels of the particular antibody that is being made can be found in the blood.
-The high serum Ig being made can make the blood viscous -> sx
-Myeloma is monoclonal so like it's only idiotype of an IgG or IgM not all of one isotype being over produced
Diagnosis of myeloma
-Monoclonal plasma cells inbone marrow
-The specific myeloma proten/Ig in the serum or urine
-Myeloma related organ dysfxn
*u need the last one cuz some elderly can get the first two normally
-One may also see excess light chains in the urine or serum
-Renal failure w/amyloidosis
-It can be hyper Ig whatever ...most common is IgG
BM biopsy of myeloma
Clinical findings are
bone fractures
pancytopenias
infections
renal failure-calcium and uric acid
hyperviscosity
What is rouleaux (rolo's) sign
In a PBS the high levels of the Ig floating in the blood will null the negative charges in the RBCs and they will stick together...pretty diagnostic
-The high levs will also stick to platelets and coag factors which may cause bleeding
Descbe myeloma cells at the level of the bone
They upreg the bone to spit out VGEF for blood
They upreg the bone to put out IL6 and TNF alpha as growth factors fro myeloma

The bigger the myeloma mass the worse the survival is
Tx for myeloma
Biphosphonates-turn down myeloma cells interaction at the bone-stim osteoblasts i think
Immunomod drugs-thalidomide and lenalidomide-works to block IL 6 and TNF alpha
Proteosome inhibitors: all cells have these but myeloma cells are more susceptible
What is waldenstroms macroglobulinemia
Some weird lymphoid-plasmacytoid cell in marrow in blood make a specific IgM but it's not a plasma cell!
-hyperviscosity, fatigue, malaise, SOB, bleeding

NO BONE LESIONS THO
What are B sx and who gets them
-Temp greater than 38
-Night sweats
-unintentional weight last over 6 months
What is serum protein electrophoesis used to dx
It is used to dx multiple myeloma w/that high Ig specific protein
How to stage a lymphoma
Use Ann Arbor staging
Stage 1-4
then A-no B symptoms
B: the lymphoma includes the presence of the B symptoms
What is APLES
It is a prognostic index for NHDG lymphoma
Age
Performance status (of the bug)
Lactate Deyhydrogenous up
Extranodal involvement
Ann Arbor Staging
What is the tx for B cell NHDG lymphoma
Chemo and rituximab
RS cells in a lymph node
RS cells in a lymph node they really stand out
if these looked more like popcorn it would be NLPHL
Nodular-lymphocyte-predominant-hodgkins lymphoma
Diffuse Large B Cell Lymphoma
What kind of lyphoma is this and what is the treatment
Follicular lymphoma-outlines of follicules.
-The progression is really slow and the disease is incurable so you watch and wait BU if the px has night sweats and loses weight then u do chemo
*This is because the follicular lymphoma can turn into a diffuse one.
If you biopsy a lymph node and you see owl's eye's what kind of lymphoma is it
Hodgekins
What is a syngeneic bone marrow transplant
A transplant from an identical twin.
Explain in bone marrow transplants why there is a 2 week window risk for infection
It is the time it takes to erradicate the old HSCs and for the new ones to start
When doing HLA matching, how many things do you have to match
3 HLA class 1 x 2
3 HLA class 2 x 2
Total of 12
Sources of stem cells
Bone marrow
peripheral blood stem cells
umbilical vein

Diseases that a stem cell transplant can cure: leukemias, myeloma,
Why are bone marrow stem cells better than peripheral blood stem cells
They are more immature and thus less likely to have graft versus host disease
What is the process of graft vs host disease
-Prechemo or radiation damages tissues that release TNF and IL1
-Transplant is performed and these cytokines supercharge the donor WBCs -> attack
-The attack is a TH1 response
Fx of graft vs host
GVH sx present in the skin liver, GI mostly due to neutrophils
Tx for GVH are steroids which make neutrophils less sticky
What is the classic side fx of mono and amoxicillin
a rash
What is the classic bug for a cough that leads to vomiting?
Pertussis

note* adults don't ge diphtheria
Name all the erythemas
Erythema migrans-lyme disease targetoid
Erythema infectiosum-parvo virus
Erythema multiforme from acute drug reaction
Name the two bugs that stupid Ixodes mosquito can carry
Babeosis and lyme disease
How do you test someone for a recent strep infection
serum for Anti-DNAase B
Describe the skin lesions for a fixed drug reaction
Perfect scattered silver dollar circles that are scattered all over
Describe viral meningitis
Normal glucose, high % of lymphocytes
What drug is better oseltamavir or rimantadine
Rimantadine has resistance so Oselt is better
Rimantadine only hits Flu A and Oselt hits A and B
What is herceptin
transtuzumab used for HER2Neu breast cancer
Male RBC
4.7-6.1 x 10^6/ uL
Female RBC
4.2-5.4 x 10^6/ uL
Adult WBC
4.8-10.8 x 10^3 / uL
PLT (platelet)
150-400 x 10^3 / uL
HGB Male
14-18 g/ dL
HGB Female
12-16 g/ dL
HCT (hematocrit) Male
42-52 %
HCT (hematocrit) Female
37-47 %
MCV (mean cell volume)
80-100 fL
MCH (mean cell Hb)
27-31 pg
MCHC (mean cell Hb conc)
32-36 %
RDW (red cell distribution width)
11.5-14.5 %
neutrophil %
50-70
lymphocyte %
20-40
monocyte %
2-9
band %
eosinophil %
0-4
basophil %
0-2
neutrophil diff
1.4-6.5 x 10^3/ uL
lymphocyte diff
1.2-3.4 x 10^3/ uL
monocyte diff
.11-.59 x 10^3/ uL
band diff
0-.7 x 10^3/ uL
eosinophil diff
0-.5 x 10^3/ uL
basophil diff
0-.2 x 10^3/ uL
WBC unopette sample volume & diluent volume
25 uL, 0.475 mL
WBC unopette diluent type
TURKS 3% acetic acid
RBC unopette sample volume & diluent volume
10 uL, 1.99 mL
RBC unopette diluent type
isotonic saline
WBC/PLT unopette sample volume & diluent volume
10 uL, 1.98 mL
WBC/PLT unopette diluent type
1% ammonium oxalate
Eosinophil unopette sample and diluent volume
25 uL, 0.775 mL
Eosinophil unopette dilution and diluent type
1:32, phloxine B
WBC unopette dilution
1:20
WBC/PLT unopette dilution
1:100
RBC unopette dilution
1:200
corrected wbc=
WBC x 100 / 100 + nrbc + dmeg
absolute counts =
diff % x cell count
manual retic counts must match by __ %
10
retic % =
retic count x 100/ 1000 rbc
Heinz body visible with __ stain
supravital
HCT =
RBC x MCV / 10
MCV =
HCT x 10 / RBC
MCH =
Hb x 10 / RBC
MCHC =
Hb x 100 / HCT
Hb x 3 =
HCT
buffy coat smear used when
wbc < 1 x 10^9 /L
eosinophilic color
red/orange
normal HCT for males
45
normal HCT for females/ children
42
Sickle cell screen detects which Hb?
S, C harlem, C z
rule of 3: Hb to HCT has to be within ___ % or less than or equal to __ from measured hCT
+ or - 3% or 3
Macrocytic MCV
Microcytic MCV
Normocytic MCV
Normoblasts (Nucleated RBC)
Reticulocyt (Supra-Vital Stains
Increased ESR On Peripheral Blood Smear ("Rouleaux Formation"
Aniocytosis (Variation In Size Of RBC)
--> Single Arrow: Small RBC
--> Large Arrow: Large RBC
Normochromic RBC's
--> Normal Hb. Conc
Hypochromic RBC's
--> Decr. In Hb
--> Incr. in Central Pallor
Hyperchromic RBC's
--> Incr. in Hb
--> Loss And/Or Decr. In Central Pallor
Polychromasia
--> RBC's with >1 Color
Spherocyte
-->Hyperchromic Circular RBC's
-->No Central Pallor
-->Associated with Hereditary Spherocytosis
Sickle Cell ("Drepanocyte")
--> Crescent shaped RBC
Tear Drop Cell ("Dacrocyte")
-->Seen in Myelofibrosis & Marrow Infiltration
Schistocyte
-->Fragmented RBC
-->Seen in any type of hemolytic anemia
Target Cells ("Codocytes")
-->Shift in Central Pallor of RBC
-->Due to a membrane abormality of incr. membrane surface area or decr. in Hg Conten
Punctate Basophilia
(Coarse Basophillic Stippling; CBC)
-->Aggregated ribosomes appear as basophillic granulations
-->Indicative Of Lead Poisoning
Howell-Jolly (H-J) Body
-->Single, Large DNA remnant in RBC
-->Seein in post-splenectomy or condtions with non-functioning spleen (Ex. Sickle Cell Anemia)
Heinz Bodies
-->Denatured Hg on inner side of RBC membrane
-->Seen in patients with G6PD Deficiency (Cannot handle oxidative stress)
Siderocytes
-->RBC's containing Iron Granules
-->Seen in patients with iron overload in body
(Ex. Thalassemia, Hematocrosis)
Normocellular Marrow
Hypocellular Marrow
-->Decr. In Cellularity
-->Incr. In Fat Cells
Hpypercellular Marrow
-->Incr. In Cellularity
-->Decr. In Fat Cells
Sideroblasts in RBC
-->Used to determine sideroblastic anemia (less common)
Microcytic Hypochromic RBC's
--> Seen in Iron Deficiency (Most Common)and Thalassemia
-->MCV < 80fl
--> Centrol Pallor is > 1/3rd the diameter
-->MCH and MCHC is also low
Macrocytic Anemica
-->MCV > 100fl
-->Also known as "Megablastic Anemia
-->Caused by Vitamin B12 & Folate Deficiency
-->Also Seen in Alcoholic Liver Disease
Megaloblast
-->Large, Nucleated Erythroid Blast
-- Hypersegmented Nucleus typical In Megablastic Anemia
Macrocytes and Macro-ovalocytes
--> Typical In Megaloblastic Anemia
--> Low Platetlets
-->High MCV
-->Hypersegmented Neutrophil
Thalassemia Major
Hgb A1: 5-20%
Hgb A2: 2-3%
Hgb F: 65-100%

-Homozy= Cooley's anemia
-Thal's: Defect in globin chain production
-Alpha chains or the beta chains
-Mediterranean origin
-Evident at 2-3 months of age (when adult hemoglobin production increases)
-Severe hemolytic anemia
-Death usually occurs in childhood or adolescence

-Considerable # NRBC (nucleated RBCs?)
-HOWELL-JOLLY bodies
-POLYCHROMATOPHILIC RBCs
-HYPOCHROMIC-MICROCYTIC
-Marked ANISOCYTOSIS
-Marked POIKILOCYTOSIS
-TARGET CELLs
Hematology:
-CBC Indices
RBC info:
- # RBCs
- Size of RBCs (MCV & RDW)
-Hgb
-Average Hgb content of RBCs (MCH, MCHC)
-hematocrit (% of blood comprised of RBCs).

WBC info:
- # WBCs
- WBC differential (WBC populations)

PLT info:
- # Platelets
- platelet volume (MPV)
WBCs & Platelets
-Functions
The overall role of WBCs is
-their function as the immune system- protection against infectious processes

Platelets have a primary role in
-blood clotting
-vasoconstriction
-vascular integrity
-secondary role as hormone serotonin carrier
[your gut is your 2nd brain!]
Total WBC Count
-Normal & Panic Ranges
Normal
-Adult/child > 2 yrs: 5000-10,000 per mm3
-Child < 2 yrs: 6200-17,000
-Newborn: 9000-30,000

Panic LOW: less than 500 per mm3
Panic High: greater than 30,000
WBC Increase
-Causes
Increase in WBCs= LEUKOCYTOSIS

-Infections
-Leukemic neoplasia
-Other malignancy
-Trauma, stress, hemorrhage
-Tissue necrosis
-Inflammation
-Dehydration
-Thyroid storm
-Steroid drugs
WBC Decrease
-Causes
Decrease in WBCs = LEUKOPENIA

-Drug toxicity
-Bone marrow failure
-Severe infections
-Dietary deficiencies
-Marrow aplasia
-Marrow infiltration
-Autoimmune disease
-Hypersplenism
-Chemotherapy
WBCs
-How they're classified
WBCs are classified by their:
-Defensive function
-Nuclear morphology
-Site of origin
-Presence or absence of specific cytoplasmic granules > special staining technique required to visualize the cells
WBCs
-Wright Stain
Appear BLUE:
-NUCLEUS & some cytoplasmic granules
-b/c cell structures with acidic groups bind the basic dye & appear blue.

Appear PINK:
-CYTOPLASM & some cytoplasmic granules
-b/c cell structures with basic groups bind the acidic dye & appear various shades of pink or red-orange.
WBCs
-Classification by granule presence & color
Granulocytes
-Classified according to staining characteristics of granules.
1. Neutrophils - Lavender
2. Eosinophils - Orange/red
3. Basophils - Blue/black
Agranulocytes - lack granules
1. Lymphocytes
2. Monocytes
Differential WBC Count
-Procedure
-Place one drop of blood S onto glass slide, spread the drop & air dry.

-Wright's Stain: A mixture of Methylene Blue basic dye and Eosin red-orange acidic dye.
-Phosphate buffer applied directly on top of stain, rinse, dry & examine.
-Oil immersion [100x] lens: count 100 WBCs
-This gives the RELATIVE # of each type of WBC, expressed as a PERCENTAGE of the 100 cells counted.
Differential WBC Count
-Calculating the Absolute # of each cell type
-"Absolute" (ABS) Number of cell type:
Important for determining if patient has a sufficient # cells of a specific type.

ABS # =
(Ttl. WBC) X Relative # of each cell type on the Diff. WBC count.

NOTE: Convert relative percentage to a decimal prior to performing calculation.
WBC Count:
-Absolute vs. Relative
Example:
-Adult with total WBC = 15,000
-WBC Diff.:
* 30% neutrophils
* 70% lymphocytes
Is this patient REALLY neutropenic?
-Abs # neutrophils = 15,000 X 0.30 = 4500
-Patient has a normal absolute neutrophil count and only has a relative neutropenia, NOT V absolute neutropenia.
WBC Development
PluriPotent Stem Cell ->
1. Lymphoid Stem Cell ->
A. Thymus > T cell
B. NK Cell
C. B cell -> Plasma Cell
2. Myeloid Stem Cell ->
A. Erythrocyte
B. Megakaryocyte -> Platelets (blood clotting)
C. Monocyte -> Macrophage
D. Granulocytes
WBC
-General Maturation Scheme
General Maturation Scheme in direction of
less mature to -> more mature

-Cytoplasm: More basophilia -> less basophilia
-Large nucleus -> smaller nucleus
-Large nucleoli -> Small nucleoli -> then absent
-Large cell size -> smaller cell size

-For granulocytes:
* nucleus large & round -> smaller & segmented
WBC
-Granulocyte Maturation
Granulocytes
-6 general stages of maturation following commitment of stem cell in bone marrow:

1. Myeloblast: Non-granular cytoplasm and red round nucleus

2. Promyelocyte: blast becomes pro when it develops distinct granules

3. Myelocyte [cell division possible through this stage]: pro becomes cyte when granules
differentiate enough to be identified n/e/b

4. Metamyelocyte: has a slightly indented nucleus

5. Band: INDENTATION MORE THAN ½ Width hypothetical round nucleus.isthmus with sides wide enough to reveal two distinct margins with nuclear chromatin visible btw them

6. Segmented cell
Picture of Myeloblast
Picture of Promyelocyte, Myelocyte, & Metamyelocyte
Picture of Band & Segmented Granulocytes
band on left, segmented on right
Granulocytes
-Classified by staining characteristics
Granulocytes
3 types of cells which have different immune
functions. Morphologically similar until
myelocyte stage.

1. Neutrophil: fine Pinkish/Lavender granules
2. Eosinophil: bright Orange/red granules
3. Basophil: dark Blue/black granules
WBCs
-Granulocytes
1. Neutrophils/PMNs
-All PMNs capable of phagocytosis
-Neutrophils are the most common PMN (polymorphonuclear leukocytes)
-are primary defense against microbial invasion
-Acute bacterial infection, inflammation, & trauma stimulate neutrophil production -> ^'d total WBC count
-Granules contain leukocyte alkaline phosphatase (LAP)
-Cytoplasm may show vacuoles during active phagocytosis
-Toxic granulation:
* Dark purple granules in cytoplasm
* mb dt severe infections, burn pts.
-Shift to the left:
* Increased Band neutrophils in peripheral circulation
+ response to bacterial infection
-Nucleus becomes hypersegmented with vitamin B12 or folic acid deficiency

Picture shows: toxic granulation in the small inserted photo and nucleus hypersegmentation in the other 3 PMNs.
WBCs
-Granulocytes
1. Neutrophils/PMNs
*Neutrophilia
Neutrophilia= Increased Neutrophils

Causes:
-Acute infection
-Trauma
-Physical/emotional stress
-Inflammatory disorders
-Metabolic disorders
-Myelocytic leukemia
-Cushing's syndrome
WBCs
-Granulocytes
1. Neutrophils/PMNs
*Neutropenia
Neutropenia = Decreased Neutrophils

-Overwhelming bacterial infection
-Viral infections
-Aplastic anemia
-Radiation therapy
-Addison's disease
-Chemotherapy
-Dietary deficiency
WBCs
-Granulocytes
2. Eosinophils
Cytoplasm contains:
-red-orange granules which:
* contain 4 proteins help that eliminate parasites:
1. peroxidase
2. major basic protein
3. eosinophil cationic protein
4. eosinophil-derived neurotoxin

-Increased cortisol levels suppress eosinophils

-Increased eosinophils in nasal smear aid in diagnosis of allergic rhinitis
WBCs
-Granulocytes
2. Eosinophils
* Eosinophilia
Eosinophilia (>5%) = increase

Causes
-Parasitic infections
-Allergic reactions
-Asthma, hay fever
-Hodgkin's Disease
-Eosinophil Myalgia Syndrome
-Eczema
-Leukemia
-Autoimmune disease
-Ovarian Cancer
WBCs
-Granulocytes
2. Eosinophils
* Eosinopenia
Eosinopenia = decrease

Causes
-Cushing Syndrome (acute adrenal failure)
-Endogenous or exogenous cortisol excess
-Stress (shock, severe burns, severe infections)

-Disappear after corticosteroid administration!!
WBCs
-Granulocytes
3. Basophils
-Known as basophils in the blood & mast
cells in the tissues
-Capable of phagocytosis of immune complexes
-Granules contain:
* heparin
* histamine
* serotonin

-Basophils and mast cells degranulate during allergic reactions, releasing histamine, etc.
WBCs
-Granulocytes
3. Basophils
* Basophilia
Basophilia (>50/mm3) = increase

Causes
-Myleoproliferative diseases: Polycythemia
-Granulocytic leukemia
-Chronic Myelocytic Leukemia (CML)
-Hodgkin's Lymphoma
WBCs
-Granulocytes
3. Basophils
* Basopenia
Basopenia (<20/mm3) = decrease

Causes
-Acute phase of infection
-Hyperthryoidism
-Stress reactions
-Prolonged steroid therapy
WBCs
-Agranulocytes
Lymphocytes - three types
1. T cells: Mature in thymus. Involved in cellular mediated immunity:
-T-suppressor cells (CD8)
-T-helper cells (CD4)
2. B cells (CD19, CD20): Mature in bone marrow. Participate in humoral immunity, produce antiBodies.

3. NK -Natural killer cells (CD56, CD57)

Monocytes
WBCs
-Agranulocytes
1. Lymphocytes
* Development
-Arise from the fixed tissue reticulum cell in the bone marrow
-B lymph. mature in BM
-T lymph. mature in the thymus
-Plasma cells = B lymphocytes that are committed to active production of antibodies

-Atypical lymphocytes: are seen in some viral infections, e.g. infectious mononucleosis
Pictures of plasma cells
WBCs
-Agranulocytes
1. Lymphocytes
* Lymphocytosis
Lymphocytosis(>4000/mm3) = increase

Causes:
-Some bacterial infections (pertussis,TB)
-Viral infections: CMV, HIV
-Lymphocytic leukemia
-Multiple myeloma
-Infectious mononucleosis/EBV
-Infectious hepatitis
-Hypoadrenalism (Addison's Disease)
WBCs
-Agranulocytes
1. Lymphocytes
* Lymphopenia
Lymphopenia (<1000/mm3) = decrease

Causes
-Non-lymphocytic leukemias
-Hodgkin's Disease
-Sepsis
-Immunodeficiency diseases
-SLE
-Drug therapies:
* adrenocorticosteroids
* chemotherapy
-Radiation therapy
WBCs
-Differential
* Normal Findings
WBCs
-Monocytes
-Arise in bone marrow from a common progenitor cell with the granulocytes
-Can be produced rapidly as needed, spend longer time in circulation
-Function as phagocytes, much the same as neutrophils do, engulf bacteria
-Remove necrotic debris from blood
WBCs
-Agranulocytes
1. Monocytes
* Monocytosis
Monocytosis (>500/mm3)= increase

Causes
-Some viral infections, e.g. infectious mono
-Chronic bacterial inf.
-Tuberculosis
-Subacute Bacterial Endocarditis SBE
-Syphilis
-Chronic ulcerative colitis
-Parasites, e.g. malaria
-Monocytic leukemia
WBCs
-Agranulocytes
1. Monocytes
* Monocytopenia
Monocytopenia <100/mm3 = decrease

Causes
-Prednisone
-HIV
-Hairy Cell Leukemia
-Aplastic Anemia
WBC:
-Response to Infection
- Increased # WBCs released from bone marrow

-Increase production from myelocyte stage in bone marrow via cell division

-Immature forms are released from bone marrow

-Band cells are most common = left shift

-Severe infections may see occasional metamyelocyte
Granulocyte Pools
1. Bone Marrow Pool: BMP
-holds a 4-10 day supply of immature forms.
-These can be released as needed as they mature.
-Immature forms seen in circulation indicate dysregulation of release mechanism

2. Circulating Granulocyte Pool: CGP
-is within the vascular tree, reflected by the WBC count

3. Marginal Granulocyte Pool: MGP
-is formed by movement of WBC to vascular walls by being attracted to trophic substances. -Once they are attached to the vessel wall they can move through the wall via diapadesis, and travel to locations where they are needed
WBC: Early Infection
-Circulating granulocyte pool (CGP) "marginates" along endothelial lining of blood vessels near infected tissues

-Extravasation of CGP "diapedesis" to Site of infection

-Rapid migration rate to tissues, in excess of marrow release rate, can result in decreased WBC count in early stages of infection

-Bone marrow responds to demand for ^ WBCs
With ^'ing bone marrow output

-the total body granulocyte pool (TBGP) ^'s, but due to continued margination, WBC count may still appear normal or decreased, aka "masked neutrophilia"

Bone marrow > CGP >>< MGP
WBC: Later Infection
-CGP and MGP finally equilibrate due to increased marrow output
-WBC count increases & left shift appears
-Indication that body is responding effectively

Bone marrow >> CGP > < MGP
WBC: Recovery from Infection
-Marrow output drops
-WBC count decreases & left shift disappears
-WBC count goes to normal

Bone marrow > CGP > < MGP
WBCs:
-Leukemoid Reaction
Leukemoid reaction:
-A nonleukemic WBC count greater than 50,000/mm3, or a differential count with NO more than 5% metamyelocytes or earlier cells.

Associated with:
-Severe bacterial infections
-severe toxic states (burns, necrotic tissue)
-marrow replacement by tumor
-severe hemolytic anemia
-severe acute blood loss
-juvenile rheumatoid arthritis
WBCs:
-Differentiating Leukemoid Reaction and Chronic Myelocytic Leukemia (CMP)
Neutrophil granules contain leukocyte alkaline phosphatase (LAP), an enzyme marker used to differentiate CML from leukemoid rxn.

-In CML: LAP is low

-In Leukemoid reactions: LAP is high

Requires special LAP stain

Picture caption:
-Left: Leukemoid Rxn w/ HIGH LAP
-Right: CML w/ LOW LAP
WBCs:
-Leukoerythroblastic Reaction
Leukoerythroblastic reaction:
-Defined by the presence of both immature WBCs and nucleated RBCs in the peripheral blood

Causes:
-Metastatic tumor in marrow - 25-30%
-Leukemia - 20%
-Myeloid metaplasia or polycythemia - 10%
-Severe infection, megaloblastic anemia, severe acute hemorrhage - about 5% each
Myeloid Metaplasia
-progressive DZ of the BM where NEOPLASTIC BM STEM CELLS lodge and grow in multiple sites OUTSIDE the BM.
-Typically, there is SPLEENIC ENLARGEMENT and a gradual replacement of the BM elements by FIBROSIS,
-progressive ANEMIA and VARIABLE changes in WBC and PLT

In Myeloid Metaplasia, there's such high demand for blood cells that you get production outside the bone marrow (in spleen & liver)
WBC:
-NRBC effect on WBC count
-Automated cell counters tally Nucleated RBCs as WBCs
* NRBC are not hemolyzed by reagents
* Need to correct total WBC count
* Correction for NRBC always lowers total WBC count

Corrected WBC =
(Original WBC Count / #NRBC + 100) X 100
-Platelet Count
-Formed in the bone marrow
-Parent cell is the megakaryocyte
-platelets are cytoplasmic fragments
-Small, round anucleate cells
-Platelets form aggregates when injury occurs to vascular endothelium to help maintain vascular integrity
-Most platelets are found in the circulating blood where they survive for 7-10 days
-25% -30% found in the spleen & liver (reservoir)
-Platelet Count
* Normal Range
Normal findings:
-Adult/elderly/child: 140,000-400,000/mm3
-Infant: 200,000-475,000
-Newborn: 150,000-300,000

Critical values (Do NOT change b/t labs):
<50,000 or >1,000,000/mm3
Thrombocytopenia
platelet count < 150,000

The danger:
-spontaneous hemorrhage.
-Counts above 40,000 rarely exhibit spontaneous hemorrage, but prolonged bleeding with surgery is common.
-At counts of <20,000 risk of spontaneous hemorrhage is severe. Petechiae (non-blanching) and ecchymosis common at this level
Thrombocytosis
platelet count > 400,000

The danger:
-As the platelet count increases, the probability of abnormal platelet function also increases, danger from thrombosis rises
Thrombocythemia
platelet count > 1,000,000

The danger:
-Not uncommon for patient to experience spontaneous bleeding & thrombosis.
-Aggregation usually abnormal
Platelet Count:
-Interfering Factors
-High altitude increases count

-Platelets have a natural tendency to clump

-Strenuous exercise may increase levels

-Decreased levels may occur prior to menses

-Estrogens increase levels

-Many drugs can increase or decrease platelets: Fischbach, p.1225-1227

-EDTA can cause platelets to form &quot;satellites&quot; around WBCs which Falsely decreases Platelet Count.

-Difficult blood draw &gt; microclots in EDTA tube &gt; Falsely decreases Platelet Count.

-Investigation of decreased Plt count should ALWAYS start with the above - ask lab to review a peripheral blood smear to check for these phenomena.

Pictures show:
-platelet satellitism due to EDTA in small pic at upper right
-platelet clumps due to microclots
Thrombocytosis
-Causes
Increased levels - Thrombocytosis

Causes:
-MALIGNANT DISORDERS, ESP. CML (malignancy is found in 50% of those with unexpected increased platelet counts)
-Polycythemia vera PCV
-Acute infections, sepsis
-POST-SPLENECTOMY syndrome = no reservoir
-Rheumatoid arthritis and other inflammatory dz
-Iron deficiency anemia
-Primary (Essential) thrombocytosis

Picture shows: increased platelet count in CML
Thrombocytopenia
Decreased levels = Thrombocytopenia

Causes
-HYPERSPLENISM
-HEMORRHAGE
-Immune thrombocytopenia
-Leukemia (EXCEPT CML)
-Myelofibrosis
-TTP-Thrombotic thrombocytopenia purpura
-ITP-Idiopathic
-Aplastic anemia
-Graves' disease
-Pre-eclampsia
-Inherited disorders
-DIC
-SLE
-Pernicious anemia
-Hemolytic anemia
-Cancer chemotherapy
-Severe infection
-Drug reactions
Mean Platelet Volume (MPV)
Normal findings: 7.4-10.4 mm3 (or fl)

-The MPV is the AVERAGE VOLUME of a population of platelets determined by an automated cell counter

-MPV relationship to platelets is the same as MCV relationship to red cells

-MPV varies with total platelet production
Mean Platelet Volume (MPV)
-In Thrombocytopenia
*with normally reactive bone marrow
*with a suppressed bone marrow
-with a normally reactive bone marrow:
* large immature platelets are released in attempt to maintain normal function (e.g., hypersplenism)

with a suppressed bone marrow:
* the platelets that are released are small & usu. immature (e.g., cancer chemotherapy)
Mean Platelet Volume (MPV)
-Interfering Factors
-EDTA anticoagulant (the standard for cell count blood samples) can create variation of up to 25% in size of platelets
Mean Platelet Volume (MPV)
-Increased Volume
* Causes
-VALVULAR HEART DISEASE
-ITP
-Sepsis
-Immune thrombocytopenia
-Severe hemorrhage
-B12/FOLATE DEFICIENCY
-Myelocytic leukemia
Mean Platelet Volume (MPV)
-Decreased Volume
* Causes
-APLASTIC ANEMIA
-Cancer chemotherapy
-Wiskott-Aldrich syndrome
What do hypersegmented neutrophils indicate?
Vitamin B12 / Folate deficiency
What do bite cells indicate?
G6PD deficiency
What do ringed sideroblasts indicate?
sideroblastic anemia
What do shistocyte or helmet cells indicate?
Microangiopathic anemia (DIC, TTP, traumatic hemolysis )
What do sickle cells indicate?
sickle cell anemia
What do spherocytes indicate?
hereditary spherocytosis, autoimmune hemolysis
What do teardrop cells in peripheral blood smear indicate?
bone marrow infiltration (i.e. myelofibrosis)
What do target cells in peripheral blood smear indicate?
HbC disease, aslenia, liver disease, thalassemia
What do howell-jolly bodies on peripheral blood smear indicate?
hyposplenia (asplenia also; occur b/c spleen doesn't RBC's like it usually would)
B12 deficiency anemia is usually caused by
malabsorption
Folate deficiency anemia is usually caused by
malnutrition
What is indicated in a microcytic anemia with central pallor?
Iron deficiency anemia (expect decreased ferritin and increased TIBC)
What is indicated in a megaloblastic anemia?
Vitamin B12 / folate deficiency
How are ferritin and TIBC (total iron binding capacity) altered in anemia of chronic disease?
Increased, decreased
In the anemia of chronice disease, would you expect iron levels in the bone marrow to be low or high?
High (think sickle cell, where body increases absorption of iron and you get iron overload)
Which two anemias cause the "crew cut skull?"
sickle cell and thalassemia
What does an increase in unconjugated bilirubin indicate?
Hemolytic anemia
What does an increase in conjugated bilirubin indicate?
Hepatitis
Reed-Sternberg Cells
Hodgkin's lyphoma
What dangerous complication do we worry about post-treatment of Burkitt's lymphoma?
Acute lysis syndrome (lysis of tumor cells releases ions; causes acute renal failure; increased LDH and uric acid confirms dx)
Rouleaux formation in peripheral blood smear
multiple myeloma
Auer rods and myeloblasts in peripheral blood smear
acute myelogenous leukemia
Lymphocytosis with smudge cells
chronic lymphocytic leukemia
Late stage myeloproliferateive complication of CML
myelofibrosis
Mechanism of heparin
activates antithrombin (decreases thrombin and Xa)
What strange toxicity do we worry about with heparin?
Heparin Induced thrombocytopenia (immune rxn to platelets; results in platelet reduction
What serious side effect do we worry about with heparin?
Heparin induced thrombocytopenia
Which measure of clotting is increased in patients on warfarin?
PT (prothrombin time or extrinsic pathway)
Which measure of clotting is increased in patients on heparin?
PTT (partial thromboplastin time)
What would an episodic hemolytic anemia indicate?
G6PD deficiency (anemia triggered by oxidative stress like TMPSMX, antimalarial drugs, fava beans)
Which demographic gets ALL?
Children (CLL is more prevalent in adults)
What does cytoplasmic blebbing ("hand mirror cells") indicate?
Acute lymphoblastic leukemia
In which disorder would you expect to see osteolytic lesions, renail failure, anemia, and hypercalcemia?
Multiple myeloma
With which infection is Burkitt's lymphoma associated?
EBV
What condition does the "M spike" on serum protein electrophoresis diagnose?
Multiple myeloma
Which chromosomal translocation is associated with chronic myelogenous leukemia?
9:22 (Philadelphia chromosome, creating the BCR/ABL protein)
What do we worry about in advanced CML?
Blast crisis (development of AML or ALL)
Why myeloproliferative disorder results in increased RBC's?
polycythemia vera
With which disease are micromegakaryocytes associated?
Myelodysplastic syndrome
What blood smear abnormality would be seen with essential thrombocythemia?
Increased platelets
What gene is upregulated in Burkitt's lymphoma?
C-myc (usually from a t(8:14) translocation)
What is indicated in a unilateral lymphadenopathy that spreads in a chain fashion?
Hodgkins lymphoma
Will LDH, AST, haptoglobin, and bilirubin increase or decrease in hemolytic states?
Increase, increase, decrease, increase

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