white blood cell dise-ses

– Hem-topoeitic stem cells: - %bility to form %ny lin%ge. - %bility of self renew%l.
– Extr-medull-ry hem-topoeisis: In stress situ%tions liver %nd spleen provide
environment for hem%topoietic development.

Leukopeni-
– Hem%topoietic stem cell is CD34 positive, then goes to either lymphoid -> b/t, or to
Myeloid -> erythrocytes/myelobl%st (neutrophils,b%sophils,eosinophils)/monobl%st/
meg%j%ryobl%st.
– low counts of WBC. Most commonly neutrophils. bec%use of infiltr%ting tumor,
necrosis, HIV, precursor suppression, meg%lobl%stic %nemi%s, r%re inherited
conditions (Kostm%nn syndrome).
– Neutropeni%: Drug toxicity (chemother%py), severe infection (“used” neutrophils).
C%n be tre%ted with GCSF or GMCSF to boost neutrophil count.
– Lymphopeni%: Immunodeficiency (Di George for ex%mple), High cortisol (induce
%poptosis in lymphocytes, such %s cushing), %utoimmune destruction (lupus th%t
m%kes p%tients produce AB %g%inst blood cells), Whole body r%di%tion
(Lymphocytes %re most sensitive to r%di%tion).
– Drug toxicity is the most common c%use of %gr%nulocytosis.

Leukocytosis
– Peripher%l leukocyte count: 1) size of precursor pools in m%rrow. 2) r%te of precursor
rele%se. 3) proportion of cells %dherent to the cell w%ll. 4) r%te of extr%v%s%tion of
cells into tissues.
– Polymorphonucle-r (neutrophilic) leukocytosis: following %cute infl%mm%tion.
b%cteri%l sepsis, tissue necrosis, high cortisol (Since there %re circul%ting
neutrophils %nd %dhered neutrophils to the blood vessels, so the ones %dhered will
be rele%sed into the blood, m%rgin%ted pool %dhesion disrupted), or severe
infl%mm%tion c%use toxic gr%nul%tions (co%rse d%rk gr%nules) %nd/or dole bodies.
(Left shift -> imm%ture neutrophils rele%sed into the blood, %nd FC receptors %re
decre%sed on them, CD16 is the m%rker for such neutrophils)
– eosinophilic leukocytosis: %llergy, p%r%site, lymphom% (Hodgkin mostly, %nd
mech%nism includes IL-5)..
– B%sophilic leukocytosis: r%re, usu-lly following chronic myelogenous leukemi-.
– Monocytosis: chronic infl%mm%tion (tuberculosis, b%cteri%l endoc%rditis, m%l%ri%)
%nd lupus, infl%mm%tory bowel dise%se, m%lign%ncy .
– lymphocytosis: %ccomp%nies the %bove monocytosis. Mostly with vir%l infections,
but one b%cteri% th%t c%uses it is Bordetell% petrusis vi% lymphocytosis promoting
f%ctor, which prevents circul%ting lymphocytes from entering lymph nodes. EBC
infection (less commonly CMV) will le%d to lymphocytic leukocytosis comprised of
re%ctive CD8 T cells. EBV prim%ry %ffects oroph%rynx, liver, B cells. The CD8 T cell
response will le%d to lymph%denop%thy (p%r% cortex since there %re the T cells),
splenomeg%ly (peri%rteri%l lymph%tic she%th of white pulp), high white count with
%typic%l lymphocytes ( ). To detect mononucleosis is Monospot test which detects
IgM heterophile -ntibodies, which usu%lly turns positive within 1 week %fter
infection, neg%tive test suggests CMV %s c%use, Definite di%gnosis is m%de by
 testing for EBV vir%l c%spid %ntigen. Complic%tions %re incre%sed risk for splenic
rupture, r%sh under penicillin %nd c%n c%use dorm%ncy of virus in B cells which c%n
incre%se risk of lymphom%.
–

Lymph-denitis
– infl%mm%tion of the lymph org%ns. Nodes enl%rged, tender, with %bscess. l%rge
germin%l centers with mitotic figures.
– Acute non specific
– Loc%lized: direct dr%in%ge. cervic%l %re% following dent%l / tonsill%r infection usu%lly.
– Systemic: b%cteremi% %nd vir%l infections, mostly kids.
– chronic non specific
– Common in %xill%ry %nd inguin%l nodes %nd not tender due to slow enl%rgement.
– Follicul%r hyperpl%si% is present. C%uses %re Rheum%toid Arthritis, toxopl%smosis,
e%rly HIV..
– to differenti%te from %denom%, we c%n see %rchitecture preserv%tion, v%ri%tion in
follicul%r sh%pe %nd size, frequent mitotic figures..
– P%r%cortic%l hyperpl%si% is c%used by stimuli th%t trigger T cell responses (viruses
like mononucleosis).
– Sinus histiocytosis (reticul%r hyperpl%si%) is often seen dr%ining epitheli%l c%ncers
(lots of m%croph%ges %re seen).

Hemoph-gocytic Lymphohistiocytosis (HLH)

– Rel-ted to m-croph-ges -nd CD8 T cell -ctiv-tion. F-mili-l or spor-dic.
– Most common for EBV!
– Associ%ted with m%croph%ges th%t %tt%ck hem%topoietic progenitors, %nd they,
%long with T cells rele%se IL-2,6,12, TNF-A which suppress hem%topoiesis more %nd
c%use infl%mm%tion, le%ding to cytopeni% %nd shock.
– clinic%lly, febrility, hep%tosplenomeg%ly. %nemi%, thrombocytopeni%, high pl%sm%
ferritin,..
– f%mili%l HLH m%y survive less th%n 2 months.

Neopl-sms
– Most white blood cell neopl%sms %re of chromosom-l tr-nsloc-tions.

Acute Leukemi-
– Leukemi%: neopl%stic prolifer%tion of bl%sts, defined %s %ccumul%tion of more th%n
20% bl%sts in the bone m%rrow. C%using %nemi%, thrombocytopeni%, neutropeni%..
so high WBC, bl%sts %re l%rge, imm%ture with % punched out nucleolus.
– Leukemi% c%n be either AML or ALL. A m%rker for lymphobl%sts (ALL) is positivity
for TdT in the nucleus. A key m%rker for myelobl-st (AML) is MPO
(Myeloperoxid%se, for oxygen dependent killing)

– ALL - %cute lymphobl%stic leukemi%. TdT positive, %bsent in myeloid bl%sts %nd
m%ture lymphocytes. Commonly %rises in children, with down syndrome %fter %ge of
5, most common leukemi% in children below 5.
– Pre-B %nd Pre-T lymphobl%sts %re morphologic%lly identic%l.
– Pre-B is most common type of ALL, expression: cd19, PAX5, CD10, CD20. Good
response to chemother%py but required prophyl%xis to scrotum %nd CSF. (t(12X21)
 –

h%s good prognosis, more common in kids. t(9X22) h%s poor prognosis, more
common in -dults.
– Pre-T ALL expression: CD1, CD2, CD5, CD7. pe%k T-ALL is in -dolescence.
Presents %s thymic m-ss in % teen%ger. in this c%se we c%ll it %cute lymphobl%stic
lymphom% since % m%ss is formed.

– AML: Acute myeloid leukomi%: ch%r%cterized by MPO, which c%n be seen %s cryst-l
-ggreg-tes of it on -uer rods. Seen %t older %dults (50-60), subcl%ssific%tions c%n
be done with cytogenetic %bnorm%lities, line%ge of myelobl%st or surf%ce m%rkers.
Cl%ssic one is -cute promyelocytic leukemi- ch%r%cterized by t(15;17), RAR
receptor disrupted (Disrubts -bility of the cells to m-ture), promyelocytes
%ccumul%te, %nd cont%in -uer rods, risk for DIC (Those rods %ctiv%te co%gul%tion
c%sc%de). ATRA is tre%tment, it binds the receptor %nd c%use the bl%sts to m%ture.
– If cl%ssified by line%ge, we divide into %cute monocytic leukemi- (monobl-sts),
l%ck MPO %nd infiltr-tes gums! Acute meg-k-ryobl-stic leukemi- is prolifer%tion
of meg-k-ryobl-sts which %lso l%ck MPO, %ssoci%ted with down syndrome
BEFORE -ge of 5.
– AML c%n %lso %rise from pre existing dyspl%si%, prior exposure to %lkyl%ting %gents
(chemother%py) or r%diother%py. Then myelodyspl%stic syndrmes develop, which is
% hypercellul%r bone m%rrow but with cytopeni- since the cells %renʼt formed
properly, donʼt go out to the blood. So bone m%rrow biopsy will reve%l incre%sed
bl%sts but less th%n 20% (so not yet leukemi%). Most p%tients die from infection or
bleeding. CAN progress to %cute leukemi% if goes %bove 20%.

Chronic Leukemi-
– Chronic: prolifer%tion of MATURE circul%ting lymphocytes. Ch%r%cterized by high
WBC count. Usu%lly insidious (slow) %nd seen in older %dults.
– CLL: Neopl%stic prolifer%tion of N-ive B cells, which co-express CD5 -nd CD20.
There is incre%sed lymphocytes %nd smudge cells on blood sme-r (spl-tted
squ-shed cells). C%n go to the lymph nodes (%s regul%r lymphocytes), %nd c%use
gener%lized lymph%denop%thy which would be c%lled sm%ll lymphocytic lymphom%
bec%use of the m%ss. Complic%tions %re hypog-mm-globulinemi- (neopl%stic
cells, no c%p%city for the IG production), %utoimmune hemolytic %nemi% (if they do
m%ke IG, they %ctu%lly produce AB %g%inst our own blood cells), tr%nsform%tion to
diffuse l%rge B cell lymphom% (pick up %ddition%l mut%tions %nd tr%nsform to it, so
enl%rged lymph node %nd spleen).
– H-iry cell leukemi-: Neopl%stic prolifer%tion of m-ture B cells, ch%r%cterised by
h%iry cytopl%smic processes. Cells %re positive for TRAP (enzyme) test. Clinic%lly
weʼll h%ve splenomeg-ly (red pulp exp%nsion), lymph%denop%thy is usu%lly %bsent.
(To remember, remember TRAP test, %nd TRAPPED in red pulp c%using
splenomeg%ly, TRAPPED in bone m%rrow c%using dry t%p with bone m%rrow
%spir%tion, %nd since theyʼre TRAPPED in %ll these pl%ces they c%nʼt go to their
norm%l loc%tion, lymph nodes, which c%uses l%ck of lymph-denop-thy). Excellent
response to % drug c%lled 2-CDA, %denosine de%min%se inhibitor, which m%kes
%denosine %ccumul%te to toxic levels in neopl%stic B cells.
– ATLL: Adult T cell Leukemi- Lymphom-: m%ture cd4 T cells, %ssoci%ted with
HTLV-1 (Virus in j-p-n -nd c-ribbe-n), present with R-sh, gener-lized
lymph-denop-thy %nd hep-tosplenomeg-ly. Also p%tients get lytic bone lesions
with hyperc-lcemi- (usu%lly multiple myelom-, but %lso here, %long with % RASH).
 – Mycosis Fungoides: Neopl%stic prolifer%tion of m%ture CD4 cells, they %ggreg%te
in epidermis, c%lled P-utrier Micro-bscesses, producing r%sh, pl%ques, nodules..
Cells c%n %lso spre%d to the blood (Sez-ry syndrome, which looks like cerebriform
nuclei since they look like % br%in)

– AID enzyme c%n induce c-MYC expression or BCL6 expression %nd c%use c%ncer.
– Incre%sed leukemi% is %ssoci%ted with down syndrome, neurofibrom-tosis, bloom
syndrome, f-lcon -nemi-, %nd -t-xi- tel-ngiect-si-.
– Viruses: HTLV-1, EBV -nd HHV-8 -re implic-ted -s c-uses.
– Environment%l %gents: helicob-cter pylori (g%stric B cell lymphom%), %nd gluten-
senstivie enterop-thy (intestin%l T cell lymphom%).
– R%diother%py, chemother%pies %nd smoking (benzene) induce AML.

Lymph-denop-thy
– c%n be p%inful, with %cute infection (the lymph nodes %re dr%ining the infection). or
p%inless with chronic infl%mm%tion, met%st%tic c%rcinom% or lymphom%.
– In infl%mm%tion, enl%rgement is due to hyperpl%si% of lymph node regions. for
ex%mple in rheum%toid %rthritis %nd e%rly HIB thereʼll be follicles exp%nsion. If
thereʼs % vir%l infection which requires strong T response, weʼll h%ve p%r%cortex
exp%nsion. Also sinus histiocytes c%n be exp%nded when % lymph node is dr%ining %
region with c%ncer.
– (reminder lymph node: Cortex B cells, P%r%cortex T cells, Medull% with sinus
histiocytes ).

– Ch%r%cteristics of ALL: %brupt stormy onset. bone p%in %nd tenderness,

hep%tosplenomeg%ly, CNS m%nifest%tions due to meninge%l spre%d.
– ALL is le%ding c%use of c%ncer de%ths in children.
– Peripher-l B cell neopl-sms
– chronic lymphocytic leukemi% (CLL) %nd sm%ll lymphocytic lymphom% (SLL)
– Morphologic%lly indistinguish%ble.. differing in lymphocytosis degree.
– most common c%use is trisomy 12q %nd deletions of 13q12-14.
– BTK inhibitors show clinic%l promise for this.
– mitotic%lly %ctive cells cluster in loose %ggreg%tes , indic%tes CLL %nd SLL.
– CLL %nd SLL cells express cd19 %nd cd20 (p%n-b) %s well %s CD5. low level surf%ce
ig expression typic%l %s well.
– CLL is the most common %dult leukemi% in the west. Lymphocyte count more th%n
4000 cells / microliter.

Lymphom%
– Neopl%stic prolifer%tion of lymphoid cells th%t forms % m%ss. either in lymph node or
extr%nod%l tissue. Divided into NHL (60%) %nd HL (40%). NHL is further cl%ssified
by cell type, size, p%ttern of growth, expression of surf%ce m%rkers, %nd cytogenetic
tr%nsloc%tions.
– M%ntle is %n %re% in the cortex (B cells) th%t surrounds the follicle. outisde of the
m%ntle sometimes thereʼs % m%rgin. Th%t helps us divide the lymphom%s to
follicul%r, m%ntle cell lymphon% %nd M%rgin%l zone lymphom%. Those %re the ones
%ssoci%ted with sm%ll (m%ture) B cells.
– Weʼll sort them from sm%ll (m%ture) cells to l%rgest (imm%ture).
 – Follicul-r lymphom- is the most common NHL in the US. involves BCL2
tr%nsloc%tions. 14/18 IgH locus tr%nsloc%tion -> BCL2 over expression by
blocking -poptosis of B cells, since we need -poptosis there to get rid of
inefficient cells. MLL2 mut%tion is %lso present in 90% of c-ses. Cells
present BCL2 protein. Gener%lized p%inless lymph%denop%thy, BM is
involved. CD20+. Tre%tment is for symptom%tic p%tients, with low dose
chemother%py or rituxim-b. complic%tions %re progression to diffuse l%rge B-
Cell lymphom%, which presents %s enl%rging lymph node. Need to distinguish
it from hyperpl%si%, by noting th%t norm%l LN %rchitecture is disrupted, thereʼs
l-ck of tingible body m-croph-ges in the germin-l center (those %re
present in infection since they come to cle%n up de%d cells when they go
through re%ctive hypermut%tion in % norm%l infection). Also we need to look
for BCL2 expression. Also % neopl%stic prolifer%tion would be monoclon%l %nd
not polyclon%l %s % regul%r infection response.
– M-ntle cell lymphom-: Neopl%stic prolifer%tion of sm%ll B cells (CD20+) th%t
exp%nd the m%ntle zone (region immedi%tely %dj%cent to the follicle), l%te
%dulthood with p%inless LAD. 11X14 tr%nsloc%tion common. Cyclin D1 over
expressed ne%r the he%vy ch%in gene. It promotoes G1/s tr%nsition in cell
cycle.
– M%rgin%l zone lymphom%: Neopl%stic sm%ll B cells (cd20+), %lso c%lled MALT
tumors (M%ltom%). in sites of chronic infl%mm%tory dise%se gl%nds in sjorgen,
thyroid in h%shimoto.. stom%ch in pylori). loc%lized. t(11/18) p%tients %renʼt
well responsive to %ntibiotics %nd b%cteri% elimin%tion.. it doesnʼt help.
– Burkitt lymphom- : Neopl%stic intermedi%te-sized B cell (CD20+),
%ssoci%tiong with EBV, c-MYC 8-14 tr-nsloc-tion (promotes cell growth %t
the he%by ch%in chromosome). Young %dults, cl%ssic%lly extr%nod%l m%ss in
J%w (Afric%n) or %bdomen (spor%dic). very %ggressive chemother%py, m%jority
c%n be cured. But if it occurs in %dults -> b%d news. “st%rry sky” %ppe%r%nce
on histology.
– Diffuse l-rge B cell lymphom- Neopl%stic l%rge B-cells (CD20+) th%t grow
diffusly in sheets. cre%tes neopl%stic follicle-like nodules. is the most
common NHL over-ll. BCL6 tr%nsloc%tion is present in 30% of p%tients.
mostly in older -dults. Huge nuclei, very -ggressive , the dise%se usu%lly
comes b%ck when “cured” %fter % while. c%n %rise spor%dic%lly or from
tr%nsform%tion of follicul%r lymphom%.

Hodgkin lymphom%
– Arises in single node or ch-in %nd spre%ds in % predict-ble w%y
%n%tomic%lly.
– Ch%r%cterized by presence of distinctive neopl-stic gi-nt cells c-lled Reed
Sternberg (RS) cells driven from germin-l centers or post germin%l center B
cells with multilobed nucleus %nd prominent nucleoli, itʼs CD15 -nd CD30
positive (Not cd20!). these cells rele%se f%ctors th%t induce %ccumul%tion of
–

the re-ctive lymphocytes, m-croph-ges, %nd gr-nulocytes th%t constitute

90% of tumor cellul-rity.
– The cells th%t constitue the beginning of the dise%se %re c%lled reed-
sternberg cells. those cells undergone both VDJ recombin-tion %nd
som-tic hypermut-tion. those cells donʼt express B cell specific genes, but
inste%d they express CD15 -nd 30.
– NF-kB tr-nscription f-ctor %ctiv%tion is common.
– RS cells %re l%rge with multi lobed nucleus or multiple nuclei, . they express
PAX5, CD15, CD30, but %re NEGATIVE for other B %nd Cell m%rkers.
– Subtypes %re nodul-r sclerosis (70%, enl%rging cervic%l neck or medi%stin%l
LN in young fem-le, RS %re present in l%ke-like (L%cun%r) sp%ced with bro%d
fibrosis b%nds), Lymphocyte-rich (best prognosis), mixed cellul-rity
(m-ny eosinophils driven by IL-5), lymphocyte depleted (worst prognosis
%nd common in elderly -nd HIV p-tients).
– Clinic%lly it presents with p-inless lymph-denop-thy, cut%neous %nergy (RS
cells c-use Th1 depletion), rel%tively well re%cting to loc-l r-diother-py.
Dise%se free surviv%l r%te is common.

– Pl-sm- cell neopl-sms

– Multiple myelom%: M%lign%nt prolifer%tion of pl%sm% cells in bone m%rrow.
Most common PRIMARY m%lign%ncy of bone. skelet-l muscle m-sses. %ge
65-70. multifoc%l destructive bony lesions. IL-6 import%nt %nd often present.
Bone involvement refers to osteocl%st %ctiv%ting f%ctor rele%sed which c%uses
destructive cells is in vertebr-te, ribs skull pelvis, femur. Incre%sed
fr-cture risk, lytics punched out lesions, %nd hyperc-lcemi- (bone broken
down rele%sing c%lcium to the blood). incre%sed %bnorm%l pl%sm% cell
numbers. erythrocytes stick together %nd form roule-ux form-tion
bec%use the red blood cell ch%rge will decre%se. CD138 molecule is found in
pl-sm- cell tumors. high levels of M (monoclon-l) proteins since
neopl-stic pl-sm- cells produce high levels of immunoglobulin, most
commonly monoclon%l IgG or IgA. Serum Protein ElectroPhoresis will reve%l
% very high g-mm- globulin pe-k, which c%n be even l%rger th%n %lbumin.
Complic%tion would be th%t those %ntibodies l%ck %ntigenic diversity since %ll
those %ntibodies recognize the s%me thing.. so infections %re most common
de%th c%use. Another complic%tion is prim-ry AL -myloidosis, over
production of light ch%in, free light ch%in circul%tes in serum %nd deposit in
tissues. Those light ch%ins c%n be excreted in the urine %s “bence jones
proteins”. Deposition of them in the kidney tubules le%ds to risk for rent%l
f%ilure (Myelom- kidney). (CRAB: C%lcium+, Ren%l f%ilure, Amyloidosis, Bone
lesions)
– monoclon-l g-mmop-thy uncert-in signific-nt (MGUS): M proteins %re
found in serum in sm%ll %mounts. Other multiple myelom% fe%tures %re
 –

missing. Common in elderly, %nd 1% c%n develop multiple myelom% of it.

– W-ldernstrom M-croglobulinemi-: B cell lymphom% with monoclon-l IgM
production. Generelized LAD, no lytic bone lesions, but incre%sed serum
protein with M spike (Due to IgM), visu%l %nd neurologic deficits (retin-l
hemorrh-ge, stroke) %nd bleeding. Pl%sm%pheresis c%uses remov%l of the
IgM %nd is % tre%tment.
– solit-ry myelom- is % solit%ry from of tumor in bone or lung, n%s%l sinuses,
oroph%rynx..
– Smoldering myelom-: p%tients %re %symptom%tic, mostly progress to
myelom% within 15 ye%rs. middle ground between multiple myelom% %nd
MGUS, M proteins found in moder%te %mounts.
– Lymphopl-sm-cytic lymphom-: secretion of monoclon%l IgM which
progresses to high viscosity syndrome W%lderstrom m%croglobulinemi%.
– H-iry cell leukemi-: middle %ged white men. point mut%tion in BRAF kin%se.
h-irlike projections on tumor cells.
– L-ngerh-ns cell histocytosis: Speci%lized dendritic cells in skin, derived
from monocytes %nd present %ntigens to T cells. Neopl%stic prolifer%tion of
them c%uses tennis r%cket gr%nules on EM, %nd they %re CD1%+ %nd S100+ by
IHC. If the subtype is c%lled on someoneʼs n%me itʼs m%lign%nt, if thereʼs 2
n%mes, itʼs seen in inf%nt younger th%n 2, %nd if 3 n%mes, then older th%n 3.
(Letterer-Siwe: m%lign%nt, skin r%sh, inf%nts less th%n 2,
–
– Eosinophilic gr-nulom-: benign prolifer%tion, p%thologic fr%cture, in
%dolescent, l%ngerh%n cells with %bund%nt eosinophils, H%nd-Schuller-
christi%n dise%se: M%lign%nt, sc%lp r%sh, lytic skull defects, di%betes
insipidus, exopth%lmos).

Myeloid neopl-sms
– Myeloprolifir-tive disorder: Dise%se of l%te %dulthood usu%lly, results in high
WBC count with hypercellul%r bone m%rrow. Cells of %ll myeloid line%ge will
be incre%sed but itʼs cl%ssified b%sed on the domin-nt myeloid cell
produced. Complic%tions would be incre%sed risk for hyperuricemi% %nd gout
(so m%ny blood cells %re degr%ded, purine degr%d%tion c%uses uric %cid
production which is %lso the c%use of gout. Those disorders c%n %lso progress
to m%rrow fibrosis (burnt out ph%se). Also c%n progress %nd tr%nsform to
%cute leukemi%.
– CML (Chronic myeoid leukemi-): Neopl%stic prolifer%tion of MATURE
myeloid cells, especi%lly gr%nulocytes, %nd b-sophils %re ch%r%cteristic%lly
incre%sed. driven by t(9X22), th%t c%uses fusion of BCR-ABL with incre%sed
tyrosine kin-se %ctivity (itʼs % sign%l tr%nsducer for growth). im-tinib is the
tre%tment (blocks tyrosine kin%se %ctivity). Splenomeg%ly is common,
enl%rging spleen suggests th%t the dise%se is getting worse. Tr%nsform%tion
 to -cute leukemi- usu%lly follows. (but c%n go to either AML (66%) or ALL
(34%). ). CML must be distinguished from leukemoid re-ction (%cute
infection), to distinguish thereʼs %n enzyme c%lled LAP (leukocyte %lk%line
phosph%t%se) which is useful for infl%mm%tion %nd wonʼt be there with CML,
CML h%ve % tendency to incre%se b%sophils, %nd CML likes to exhibit the
%bove mentioned t(9;22).
– Polycythemi- Ver-: prolifer%tion of m%ture myeloid cells, especi%lly RBCs.
Gr%nulocytes %nd pl%telets %re %lso incre%sed. Associ-ted with JAK2 kin-se
mut-tion. Blood is lo%ded with RBC %nd becomes very thick with high
viscosity which c%uses blurry vision %nd he%d%che, incre%se risk of venous
thrombosis (bud-chi-ry syndrome, which is % thrombus in the hep%tic vein
which results in infr-ction of the liver). Another complic%tion is % flushed
f-ce due to congestion %nd itching %fter b%thing (bec%use MAST cells %re
%lso incre%sed). Phlebotomy is % tre%tment. PV must be distinguished from
re%ctive polycythemi% (lung dise%se for ex%mple, with hypoxi% %nd
erytropoeitin work), so we check EPO, %nd oxygen in blood. (Ren%l cell
c%rcinom% for ex%mple secretes Epo, but oxygen would be norm%l). In PV
Oxygen is norm%l %nd EPO decre%sed.
– Essenti-l Thrombocythemi-: Neopl%stic prolifer%tion of m%ture myeloid
cells, especi%lly pl%telets. RBC %nd gr%nulocytes %re %lso incre%sed. JAK2
mut-tion indic%ted %s well. A simil%r p%ttern would be iron deficiency %nemi%.
Incre%sed risk of bleeding %nd/or thrombosis. C%n r%rely progress to m%rrow
fibrosis (burn out) or %cute leukemi%. No signific%nt risk for hyperuricemi- or
gout.
– Myelofibrosis: Neopl%stic prolifer%tion of m%ture myeloid cells, especi%lly
meg-k-ryocytes. Also JAK2 kin%se mut%tion. Those meg%k%ryocytes
produce PDGF (pl-telet derived growth f-ctor) which c%uses the fibrosis.
Splenomeg-ly due to extr-medull-ry hem-topoiesis (bone m-rrow
fibrosed, so hem-topoeisis goes b-ck to spleen), Leukoerythrobl-stic
sme%r (reticulin g%tes usu%lly prohibit imm%ture cells to exit to the blood, but
in the spleen those g%tes %re not re%lly there, so white %nd red imm%ture cells
%re incre%sed), incre%sed risk of infection, thrombosis %nd bleeding (Since
not enough red & white cells %re produced). In myelofibrosis there is %lso
incre%se risk to develop te-rdrop cells, since some of the bone m%rrow still
works, %s the RBCs %re gener%ted, theyʼll be stretched when trying to le%ve
bec%use of the fibrosis %nd squeezed to this sh%pe.