Heme #2 Exam #2

CYTOGENETICS

cytogenetics

-study of the structure of chromosomes an the relationship between chromosome abnormalities and diseases states

-congenital: effects every cell in the body

-mosaic abnormalities are only sen in some cells or tissues, depending on when it happened in embryonic development

-acquired: after birth where a stem cell becomes genetically abnormal

abnormal cells often undergo functional changes that improve their ability to survive and reproduce like:

-loss of contant inhibition

-loss of apoptotic potential

-increased growth factor recognition

-loss of tumor supressor gene expression

-increased cell cycle progression

Chromosome basics

-46 in normal cells (23 homologous pairs)

-22 sets are autosomal

-2 sex chromosomes (XX or XY)

centromere

-heterochromatin, very repetitive sequences

-although repetitive, each centromere has its own unique sequence

-kinetochore forms at the centromere during cell division and is the attachement point for spindle fibers

-sister chromatids join at the centromere

-chromosomal segments without centromeres are lost during cell division

telomere

-tip of the chromosome

-protective cap to prevent degredation

-composed of repetitive TTAGGG sequences

satellite chromosome region

-only in chromosomes 13-15, 21,22

-small dots at the tip of the P arm

-contains coding regions for rRNA

-assists in building nucleioli

-p arms are above centromere (short)

-q arms below centromere (longer)

nucleotides

-Basic units of DNA molecule

COMPONENTS:

1) 1/4 nitrogenous bases (ACTG)

2) phosphate group

3) 5 carbon sugar (ribose)

double-helix

Shape of DNA

nucleosome

-DNA coiled around histones

histone

protein molecule around which DNA is tightly coiled in chromatin

gene

chromatin

-nucelosomes twist and wrap to become chromatin

chromosome

-nucleic acids and protein together

transcription vs translation

DNA --> mRNA in nucleus is transcription

mRNA --> tRNA --> AA --> protein is translation

euchromatic regions vs heterochromatic regions

EUCHROMATIN:

-lightly staining because loosely coiled

-active gene transcription

-rich in GC nucleotides

HETERCHROMATIN:

-darkly staining with G-banding because tightly coiled

-low active gene #

-rich in AT nucleotides

metacentric

-centromere in middle

-equal P and Q

sub-metacentric

-centromere off center

-shorter P than Q

acrocentric

-centromere close to end

-forms satelleties

deletion

-loss of material from chromosome

-interstitial: within an arm, no telomere involvement, requires 2 breaks

-terminal: involves telomere, requires 1 break

duplication

-exact segment is present twice usually right next to each other

translocation

-exchange of material betwen 2 chromosomes

-Balanced/reciprocal: 2 chromsomes exchange a segment

-Unbalanced: segment of one is moved to another without receiving something in return

-Robertsonian- fusion of two acrocentric Q arms

inversion

-segment of chromosome flipped within itself

-pericentric: includes centromere

-paracentric: no centromere included

ring chromosomes

-two breaks occur, one in each arm of the chromosome

-telomeres are lost and the remaining ends are fused

isochromosome

-break occurs just below the centromere so one chromosome is lost

-tips of remaining q arms fuse together and when chromosome lengthens again it is like a mirror image

aneuploidy

Abnormal number of chromosome (any deviation from 2n, not a multiple of n though so like +/- 1

polyploidy

-an extra set of chromosomes (multiples of n)

triploidy is 3n gaining an extra of ALL

hyperploidy

higher than 2n but not a mulitple of n (aneuploidy?)

hypoploidy

-lower than 2n but not a multiple of n

pseudoploid

cell with 46 chromosomes but not normal (46, XX, -7, +21 i think means missing a 7 but an extra 21)

trisomy

gain of an extra chromosome (1,1 --> 1,1,1,)

nomenclature

chromosome # --> arm --> region --> band --> sub-band

monosomy

loss of chromosome (1,1 --> 1)

Nomenclature Rules

1. total # of chromosomes COMMA

2. sex chromosome complement (XX, XY, XXY, etc.) COMMA

3. parenthesis are around chromsome # and breakpoints of abnormal chromsomes

4. if sex chromsome is abnormal, put the normal one first, follow that with a comma, and description of the abnormal sex chromsome

EX: 46, X, del (X) (p22)

5. it autosome is abnormal, follow sex chromosome naming with a common and then follow that with description of the autosomal abnormality

EX: 46, XX, del(5)(q13q33)

EX: 48, XY, +8, +21

EX: 46,XY,t(9;22)(q34;q11.2)

EX: 46,XX,inv(16)(p13.1q22)

6. when describing single abnormal chromosomes, no puncutation should separate the breakpoints or any other part of description

7. semicolons are used to seprate the chromosome and the breakpoints of a translocation since you are describing 2+ chromosomes

ABBREVIATIONS:

-del = deletion

-one breakpoint is used if terminal

-two breakpoint is used if interstitial

-inv = inversion, requires 2 breakpoints

-t = translocation

-dup = duplication

-i = isochromosome (breakpoint is at center of the mirror image)

-r = ring chromosome

-mar = marker chromosome

cell cycle

1. Interphase

-G1 (growth and metabolism)

-S (DNA synthesis)

-G2 (prepare for cell division)

2. Mitosis

P - chromatin condenses, nuclear membrane degrades

M - chrosomes move to equator

A - sister chromatids pulled apart by spindle fibers

T - nuclear membrane reforms

3. Cytokinesis

-cell membrane reforms around organelles and new DNA

homologous chromosomes

Pair of chromosomes that are the same size, same appearance and same genes.

specimens used in cytogenetics

-blood for constitutional and acquired abnormalities

-bone marrow and lymph nodes - acquired only

-amniocytes and chorionic villi

-productions of conception (miscarriage)

-tumors -acquired

-CSF - acquired

-sodium heparin is best for anticoagulant!!

-PHA added to promote division of T-lymphs

-colcemoid added to arrest cells in metaphase

-hypotonic solution added to increased cell volume

-centrifuged and supernatant is drawn out

-fixitive added

-fixative repeated after centrifuging and supernanat removed again

-pellet is then resuspended and a drop of specimen is put on the slide and allowed to dry (too fast, overlap, too flow =overspread)

-use phase micrscopy to see

FISH

-fluorescent in situ hybridization

-molecular cytogenetics

-uses fluorescent dye molecules bound to DNA and then hybridized to patient DNA

ADVANTAGES:

-metaphase or interphase cells

-identifies very small anomalies

-does not require living cells, just intact DNA

-larger sample size since analysis is less time consuming

DISADVANTAGES:

-longer analysis and turn around time?

-limited to regions where the probes hybridize

-results can be misleading if done wrong

types of FISH probes

-centromere: hybridize to the alpha satellite region of chromsome

-locus-specific: hybridize to specific euchromatic sequence (identifies deletions, translocations, inversions)

-whole-chromosome paints: for a specific chromosome to identify chromsome segments of unknown origin

-sub-telomere: hybridize sequences just proximal to the actual telomeres

-multi-color paints (M-FISH): allow for a karyotype that depicts each autosomal pair and sex chromosomes in own color!

BCR-ABL protein in CML

-production of a hybrid/chimeric protein

-chronic myeloid leukemia

-BCR-ABL protein in CML behaves very different from the normal tyrosine kinase that is encoded by the ABL region

**meaning it never becomes INactive (always active)

**inhibits apoptosis

**becomes less adhesive so released early from BM

-on chromsomes 9 and 22

Chronic Myeloid Leukemia Lesson #11

myeloproliferative neoplasm definition

-acquired hematopoietic neoplasms that have unregulated differentiation and proliferation of stem cells

-in BM and PBS

-affect all 3 cell lines

4 main classifications of MPNs + 3 extra for WHO

GENERAL:

1 - chronic myeloid leukemia (chronic myelogenous leukemia)

2 - primary myelofibrosis

3 - polycythemia vera

4 - essential thrombocythemia

WHO ADDS:

1 - chronic neutrophilic leukemia (CNL)

2 - chronic eosinophilic leukemia (hypereosinophilic syndrome) (CEL/HES)

3 - myeloproliferative neoplasm unclassifiable (MPN-u)

main features of MPNs

-gradual onset

-middle age, older adults (but can happen in younger)

CLINICAL:

-hemorrhage

-thrombosis

-infection

-pallor

-weakness

HEMATOLOGICAL:

-anemia or polycythemia

-LE picture

-leukocytosis

-basophilia

-thrombocytosis (maybe bizarre too)

BONE MARROW:

-hypercellular

-eventually becomes fibrotic with increased reticulin fibers

-when this happens, hematopoiesis moves extramedullary to spleen or liver

Chronic Myeloid Leukemia (CML, one of the 4 main MPNs)

-uncontrolled proliferation of cells mainly granulocytes

-20% of all leukemias

-middle aged usually, peaking 40-60

3 Phases of CML

chronic

accelerated/intermediate transitional/aggressive

blast

chronic phase of CML

-usually presents in this phase

-splenomegaly and leukocytosis

-abdominal pain due to enlarged spleen is important

-left shift with MYELOCYTE BULDGE and basophilia

-few symptoms, usually seen during general exam

-arthritis bc of gout can occur

-controlled with medication regulating fatigue and complications like leukocytosis, splenomegaly, anemia

-lasts 2-3 years but can last long with new treatments

Accelerated phase of CML

-aka intermediate transitional or aggressive phase

-AGGRESSIVE

-10-19% myeloblasts in PBS or BM

->20% basophils in PBS

-lasts 1-1.5 years

-harder to control

-symptoms add bone pain and fever

-additional chromosome abnormalities appear

-medication response is poor resulting in more blasts, promyelocytes, and basophils, low platelets, uncontrollable splenomegaly

Blast Crisis phase of CML (acute leukemia phase)

-BM has >30 or >20% blasts depending on FAB or WHO

-skin or tissue infiltration (extramedullary)

-most blasts are myeloid but 1/3 cases can have lymphoid phenotype

-extreme basophilia and thrombocytosis

-additional chromosome abnormalities are found

-hard to treat, lasts 3-6 months

PBS in CML

-leukocytosis with LEFT SHIFT

-increased in all granulocyte precursors including blasts

-promyelocytes and blasts are usually less than 10% though

-absolute eosinophilia or basophilia

-N/N mild anemia

-platelet counts can be L or N or H

BM in CML

-90-100% hypercellular because of proliferating myeloid precursors

-ME ratio can be 10-100:1

-less than 20% blasts

-Auer rods are unusual to see unless in blast crisis phase

-reticulin stain can show mild fibrosis (where BM elements are replaced with connective tissue)

-megakaryocytes prominant

Chromosome Abnormality in CML

-PHILADELPHIA CHROMSOME (gold standard)

-reciprocal translation between chromosome 9 and 22

-t(9;22)(q34;q11)

-this translocation relocates the oncogene ABL from 9 to 22 in the bcr region

-results in 9 being longer than usualy

-results in 22 being shorter than normal (PHILADELPHIA)

-acquired

-BCR/ABL fused gene can be see with FISH or molecular testing

-you need to see this chromosome abnormality to call it!

-Philadelphia then codes for an abnormal protein called p210 that enhances tyrosine kinase activity which very much supresses apoptosis and increases cell production!

Fish Testing in CML

-test for Philadelphia chromosome

-fluorochrome labeled DNA probes for metaphase cells

-red probe for ABL on chromosome 9

-green probe for BCR on chromosome 22

-IF +: red and green probe are right next to each other (called yellowish fusion signal)

In 95% of CML patients is the philadelphia chromosome, the other 5% have the bcr/abl translocation.

IF NO PHILADELPHIA: they will have poor response to therapy, no basophilia, thrombocytopenia, short survival

LAP score for CML

-Leukocyte Alkaline Phosphatase found in granules of neutrophils segmented and band

-LOW LAP SCORE bc many immature neutrophils which have lower scores

-CML < 40!! (help rule of PV and other MPNs)

treatment for CML

-goal to eliminate all cells containing philadelphia chromosome

-treatments vary by age, BM donor availability, etc.

-Gleevec-imatinib mesylate is treatment of choice now

-allogenic BM transplant after

GIM: improves duration of chronic phase bc it's a tyrosine kinase inhibitor to slow growth, inhibit proliferation, and induce cell death

ALLOGENIC BM TRANSPLANT: transplant is the only known cure for CML usually done in <55 year olds. high mortality rate with this though

leukocyte apheresis can lower WBC if >300 where whole blood takes out the WBCs to temporarily reduce WBC

prognosis of CML

-highly responsive to treatment in the chronic phase

-survival in accelerator phase <1 year

-survival in blast phase ~few months

DETERMINED BY:

-age, symptoms, splenomegaly, anemia, negative philadelphia chromosome, high or low platelets, low megakaryocytes, basophilia, myelofibrosis

-short duration of remission, longer time to reach remission, poor suppression of philadelphia-positive cells by chemo

Chronic Neutrophilic Leukemia

-rare MPN

-leukocytosis WITHOUT immature granulocytes

-elevated neutrophil count

-hypercellular BM, granulocytic hyperplasia

-philadelphia chromosome negative

-LAP increased

-need to rule out other causes of neutrophilia and CML

Chronic Eosinophilia Leukemia (hypereosinophilic syndrome)

-high eosinophils (>1.5), in BM, blood, tissues

-organ and tissue damage because of charcot-leyden crystals that form

-LAP normal

-philadelphia negative

-poor prognosis

-rule out other causes of high eosinophils

-look for signs of organ and tissue damage

LESSON 12: Polycythemia Vera

I love you! You did that other lesson in less than an hour :) do this one and then make cards for them all so far! then done for the day!!

Polycythemia is

increased RBCs

polycythemia vera is

-a MPN with unregulated increased of RBCs in the PBS and BM

-increase in RCM (Red Cell Mass), RBC count, or HGB

*could also have WBC and PLT increases too

relative vs absolute polycythemia

RELATIVE: decrease in plasma volume so more concentrated

ABSOLUTE: increase in red cell mass

3 groups of polycythemia

1. Polycythemia Vera: increase in RBC mass; unregulated production of RBCs due to a clonal hematopoietic stem cell disorder

2. Secondary Polycythemia: increased in RBC mass; explainable or apparent increase in RBCs (smoking, high altitudes)

3. Relative Polycythemia: decreased plasma volume with normal or low RBC mass (dehydration, burns, etc.)

pathophysiology of PV

-stem cell defect causing unregulated and accelerated erythropoiesis

-stem cells are sensitive and very responsive to erythropoietin

Clinical findings of PV

-40-60 year olds

-more males than females

-gradual onset

-increased RBC mass leads to symptoms like blood thickening, headache, visual disturbances, weight loss, itchy skin, venous or arterial thrombosis

-splenomegaly and hepatomegaly with progression

-thrombosis or hemorrhage

-hypertension due to thickened blood

-platelet abnormalities possible

-plethora (red complexion) due to increased RBCs

-can lead to myelofibrosis or acute leukemia

PBS findings for PV

-RBC 6-10

-HGB >18

-hematocrit (>55%)

-increased RBC mass

-N/N cells

-reticulocytes could be slightly elevated

-leukocytosis (12-20) without fever or infection

-neutrophilia with mild left shift

-LAP >100

-thrombocytosis >400 (abnormal morphology and function too)

*if advanced, could also have

Myelofibrosis (LE anemia, dacrocytes)

Acute Leukemia (anemia, low plts, blasts)

BM findings for PV

-not necessary to diagnose PV but is common practice to diagnose

-hypercellular with lots of erythroid and myeloid precursors

-normoblasts may collect in large clusters

-megakaryocytes are increased and enlarged with lobulated nuclei

-fibrosis may be present so reticulin stain is helpful

-iron stores are reduced or absent because it's all being used to make all the RBCs

LOOK AT TABLE/WKSHT TO SEPARATE THE 3!!!

other lab findings in PV

-oxygen sat normal

-erythropoietin levels low bc the body sees all the cells being made, but this doesn't stop PV from making lots of cells still

-URIC ACID INCREASED (due to turnover of NAs from RBCs, could lead to gout)

-Vitamin B12 increased

-25-50% have cytogenetic abnormalities

-JAK2 gene mutation (95% have this!!!!!)

**it is common for PV to have IDA too so high RDW, microcytosis, elliptocytes even with high RBC/Hgb

***thalassemia also has high RBC but PLTs have normal morphology (here they are high and abnormal morph). Thal also doesn't have basophilia

PV JAK2 Gene Mutation

95% of patients have this so helps diagnose

Therapy for PV

-no cure but tx prolongs survival

-therapeutic phlebotomy is the 1st choice of tx though it reduces iron supply and blood volume

-myelosuppressive therapy can be used along chemo or radiation to extend quality and length of life

-untreated have survival 6-18 months are dx

-treatment can be >10 years

-thrombosis is a common complication and major caused of death in PV

-15-20% go to myelofibrosis

-15-20% go to acute leukemia

Secondary Polycythemia

-increased in RBC mass with no changes in other lines

CAUSES:

-increased erythropoietin bc of hypoxia, high altitudes, COPD

-tumors excreting erythropoietin

-familial polycythemia (high oxygen affinity hemoglobins so less o2 to tissues)

-neonatal polycythemia bc of intrauterine hypoxia

-defective o2 transport bc of smoking or pollution in environment

relative polycythemia

-dehydration, hemoconcentration or GAISBOCK'S syndrome

-high Hgb and Hct bc of low plasma volume

-STRESS erythropoiesis = Gaisbock's syndrome found in hypertensive, overweight nervous males that smoke and drink alcohol

-WBC, platelets, iron stores, O2 sat, and BM cellularity are all normal. cytogenetics normal too

PRIMARY MYELOFIBROSIS & ESSENTIAL THROMBOCYTHEMIA

Primary Myelofibrosis

-MPN with unregulated proliferation of hematopoietic cells AS WELL AS extramedullary hematopoiesis and systemic bone marrow fibrosis

*aka chronic idiopathic myelofibrosis, etc.

-though to happen when a defect or mutation occurs in the hematopoietic stem cells.

-all 3 cell lines CAN be affected by typically it is only two

-as BM becomes fibrotic, the liver and spleen take over hematopoiesis and become enlarged

clinical findings in myelofibrosis

-50-70 year olds

-gradual onset and can be asymptomatic at first

-then fatigue, weakness, bleeding/bruising, night sweats, extremity pain, bone pain, pain in ULQ because of enlarged spleen, gout, renal stones

-

lab findings in primary myelofibrosis

-LE picture

-N/N anemia with DACROCYTES, nRBCs, anisocytosis, polychromasia, basophilic stippling

-WBC can be variable with some blasts, immature granulocytes, and maybe high baso and eos

-LAP score normal (maybe slightly elevated)

-NO PHILADELPHIA

-platelets variable, could be atypical, bizzare, large, hypogranular

-low PLTs come with disease progression, could see circulating micromegakaryocytes (those cells with platelets blebbing off looks just like a nucleus!!!)

-could become panctyopenic with progression

BM findings in primary myelofibrosis

-fibrosis in the BM makes aspirations hard and result in a dry tap (aspirate with no units)

-hypercellularity and fibrosis

-clusters of large, atypical megakaryocytes may be seen

Reticulin Stain

-demonstrates reticulin fibrosis in MPNs and HairyCellLeuk

-reticulin fibers stain black and it is graded

0 = no fibers

1 = occasional

2 = fibers throughout most, no coarse

3 = diffuse fiber netweork with ropy coarse fibers, no mature collagen

4 = diffuse, coarse fiber with some collagenization

other lab findings in PMF

-alkaline phosphatase increased

-lactate dehydrogenase increased

-uric acid elevated (like in PV)

-B12 elevated (like in PV)

Prognosis/Therpay for PMF

-no cure, survival 4-5 years

-worse prognosis of all MPNs

-infection, thrombosis, hemorrhage are common causes of death

-10-15% go to an acute leukemia

-Tx reduces symptoms so like blood transfusions for anemia, androgens/corticosteroids, chemo to reduce spleen size and fibrosis, radiation to reduce spleen size, thalidomide to reduce spleen size, splenectomy, stem cell transplant (allogenic)

-MYELPHTHISIC anemia is similar and should be ruled out (breast cancer specifically i remember about this)

DIAGNOSE:

-fibrosis >1/3 of BM

-splenomegaly

-LE picture

-no increased RBC mass

-no phil + chromosome

Essential Thrombocythemia (ET)

-affects megakaryocytes

-PBS shows platelets >1000

-thrombosis and hemorrhage are common

-can affect all 3 cell lines though, platelets are just more affected

clinical findings in ET

-50-60 year olds

-bleeding or bruising/nose bleeds

-thrombosis

-slight splenomegaly

-headache, dizziness

-weight loss

lab findings in ET

-PLT >600, usually >1000

-PLTs are mostly normal looking but some giant or hypogranular are possible

-might see megakaryocyte fragments

-ABNORMALLY FUNCTIONING PLTs

-anemia proportionate to bleeding, so N/N anemia with some anisopoikilocytosis possible

-WBC usually normal, maybe elevated (dif normal, maybe some high eos and baso)

-LAP normal to increased

-no philadelphia chromosome

BM in ET

-megakaryocytes are increased and clustered in BM

-enlarged megs with more lobulation

-hyperplasia in megs and some granulocytes too

-if hemorrhaging, PT could have increased RBCs too

-"marked hyperplasia in all 3 cell lines" according to the lab

-iron stains have normal to increased iron

other testing in ET

-B12 increased

-uric acid increased

-LDH increased

-cytogenetic abnormalities are rare but could

-molecular gene:

1) 65% have JAK2

2) 20 have CALR

3) 5 have MPL

4) 10 are triple negative

Prognonsis and therapy for ET

-life is normal but bleeding and hemorrhage could cause death

-ET can go to PV or acute leukemia overtime

-therapy to reduce thrombosis complications and lower PLTs

-palteletpheresis works well and anticoagulants like aspirin can inhibit platelet function

-anagrelide is an antiplatelet drug that works well

Et differential diagnosis

-need to differentiate from reactive or secondary thrombocytosis

-reactive thrombosis is usually caused by an infection, inflammation or carcinoma

Reactive

-PLT can reach 1000 but only temporarily

-WBCs are RBCs are normal in reactive thrombocytosis but not in ET always

-splenomegaly is not in reactive

-PLTs function normally in reactive

ET diagnostic criterai

-thrombocytosis >600

-megkaryocytic hyperplasia

-no causes for reactive thrombocytosis

-no philadelphia chromosome

-hemoglobin <13 or normal RBC mass

-stainable iron in BM

-no fibrosis in BM

-no LE picture

MPNs differentiating them!

-high RBCs can help show CML vs PV

-ET has high PLTs but so can PV but RBCs won't be high

-PMF has really high RECTIC fibers in BM

-basophilia is mostly in CML

Starting Myelodysplastic Syndromes (MDS)

myelodysplastic syndromes (MDS)

-stem cell disorders distinguished by PB cytopenias and dysplastic changes in the BM

-BM hyperplasia with INEFFECTIVE hematopoiesis are why you get cytopenias (BM is producing cells but they are being destroyed before reaching the PB)

aka MDS =

-smoldering leukemia

-preleukemia

-dysmyelpoietic syndrome

MDS with FAB are characterized by

-% of blasts in BM

-% of blasts in PB

-if ringed sideroblasts are there or not

-% of mononcytes present

-extent of cytopenias

-degree of dyspoiesis

5 types of MDS according to fab

- Refractory Anemia (RA)

- Refractory Anemia with Ring Sideroblasts (RARS)

- Refractory Anemia with Excess Blasts (RAEB)

- Refractory Anemia with Excess Blasts in Transformation (RAEB-t)

-Chronic Myelomonocytic Leukemia (CMML)

**FAB doesn't include newer diagnostic methods like WHO does, so WHO is used more

WHO uses more

morphology, clinical, molecular, cytogenetic, and immunophenotypic features

WHO Groups of MDS

-MDS with single lineage dysplasia (MDS-SLD)

-MDS with ring sideroblasts (MDS-RS)

-MDS with multilineage dysplasia (MDS-MLD)

-MDS with excess blasts (MDS-EB-1 or MDS-EB-2)

-MDS with isolated del (5q)

-MDS, unclassifiable

the revision in 2016 with WHO Classifications was

name change from refractory anemia to MDS

Etiology/Causes of MDS

-stem cell defect that causes abnormal maturation and function of hematopoietic cells

-premature destruction (ineffective hematopoiesis) causing cytopenias in the blood

-often idiopathic but can be caused by chemo/radiation, benzene, smoking, viruses

**very common acquired BM failure syndromes in adults!

PBS in MDS

WHITE BLOOD CELLS

-neutropenia

-monocytosis possible

-early blasts, promyelocytes, myelocytes, and metas

-dysplastisc features, hypogranular neutrophils, pseudo-pelger huet nuclei, enzyme defect in neutrophils, ring-shaped nucleus

**pseudo means not every nuetrophil will be round or dumbell shaped, usually more round when acquired)

**hypogranular neutrophils can look like monocytes but less blue cytoplasm, more pink

**ring nucleus in neutrophils

**LOW LYMPHS

*monocytosis can happen in many MDS i think??

RBCs

-macrocytic anemia

-oval macrocytes

-dimorphic RBCs

-low reticulocytes

-anisocytosis,poikilocytosis (dacrocytes possible)

-nRBCs

PLTs

-any count possible

-giant, hypogranular, or fused plts

-abnormal adhesion and aggregation

Clinical Findings in MDS

-weakness/fatigue bc of anemia

-bleeding/easy bruising bc of low platelets

-infection bc of neutropenia

CMML will have hepatosplenomegaly but the others won't!