anemia determining the cause
TRANSCRIPT
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Anemia: Determining the Cause
by Wendy Fleischman, DVM, DACVIM June 2012 V!l "#, $! %&
Abstract
Anemia is a common finding in small animal practice; however, the multitude of potential
causes can make determining the underlying diagnosis a challenging and frustrating endeavor.
With a basic understanding of red blood cell production and a systematic diagnostic approach,
clinicians should be able to clearly define the cause of anemia in most cases.
Anemia re'ers t! a reduced hem!gl!bin c!ncentrati!n due t! decreased red bl!!d cell mass(
)his can be e*+ressed as a +aced cell -!lume .CV&, hemat!crit, red bl!!d cell /C& c!unt,
!r hem!gl!bin le-el bel! the re'erence inter-al( F!r sim+licity, hemat!crit !r .CV ill be used
in this article(
Erythropoiesis and Erythrokinetics
A basic gras+ !' /C +r!ducti!n can c!ntribute much t! understanding the causes !' anemia(
In adult mammals, /Cs are +r!duced +rimarily in the b!ne marr!(1 )he /C mass can be
di-ided int! '!ur +hases !r c!m+artments: stem cells, +r!genit!r cells, +recurs!r cells, and
mature erythr!cytes(2 A diagram illustrating the de-el!+ment !' /Cs is +r!-ided in FIGURE
1 .
Stem Cells
)he hem!+!ietic stem cells are a small +!+ulati!n !' unc!mmitted, sel'reneing germ cells(
)hese cells can gi-e rise t! all ty+es !' bl!!d cells erythr!cytes, leu!cytes, and +latelets&(
In3ury t! the stem cell c!m+artment is an unc!mm!n cause !' anemia( In such a situati!n, the
anemia is acc!m+anied by de'iciencies in the !ther t! cell lines, a c!nditi!n re'erred t!
as aplastic anemia, !r, m!re c!rrectly, aplastic pancytopenia( /e+!rted causes !' a+lastic
+ancyt!+enia are listed inBOX 1("45
BOX 1. Reported Causes of Apastic Ane!ia "Apastic #ancytopenia$ in %o&s and
Cats'()
Infectious a&ents
• .ar-!-irus
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• Ehrlichia s++
• Anaplasma s++
• Fe6V
• FIV
%ru& effects*hor!ones
• 7y+erestr!genism e*!gen!us !r end!gen!us&
• Chem!thera+eutics, a8athi!+rine, hydr!*yurea
• 9rise!'ul-in, 'enbenda8!le, albenda8!le
• )rimeth!+rimsul'adia8ine, chl!ram+henic!l
• Methima8!le
• .henylbuta8!ne
• )hiacetarsamide
• ;uinidine
Radiation
Idiopathic*i!!une+!ediated
,yeophthisis
• $e!+lasia
• Fibr!sis
Progenitor Cells
7em!+!ietic gr!th 'act!rs dri-e +luri+!tent stemcells t! bec!me +r!genit!r cells c!mmitted t!
a s+eci'ic cell line( )he cyt!ines and h!rm!nes in the cells< en-ir!nment then
dri-e'urtherdi''erentiati!n and +r!li'erati!n !' the +r!genit!r cells(In the case !' erythr!cyte
+r!genit!r cells, the h!rm!ne that causes di''erentiati!n and +r!li'erati!n is
erythr!+!ietin(%
=rythr!+!ietin is +r!duced by renal interstitial cells in res+!nse t! renalhy+!*ia(> =rythr!+!ietin inhibits a+!+t!sis +r!grammed cell death& !' the erythr!id +r!genit!r
cells, all!ing them t! di''erentiate int! erythr!id +recurs!r cells and, e-entually, mature
erythr!cytes( 6ac !' erythr!+!ietin !r an inability !' the +r!genit!r cells t! res+!nd t!
erythr!+!ietin are c!mm!n mechanisms leading t! n!nregenerati-e anemia(
Precursor Cells
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.recurs!r cells are 'ully c!mmitted t! !ne cell lineage and mae u+ m!st !' the cells ithin the
b!ne marr!( )hey de-el!+ al!ng a +re+r!grammed +athay !' +r!li'erati!n and
maturati!n(2Maturati!n and release !' erythr!cyte +recurs!r cells can be en!rm!usly
accelerated in res+!nse t! erythr!+!ietin( ?nc!mm!nly, -itamin de'iciency !r c!ngenital
hem!gl!bin !r cyt!seletal de'ects can lead t! dys'uncti!nal maturati!n !' the +recurs!r cells,hich can result in n!nregenerati-e anemia(@, Destructi!n !' +recurs!r cells, such as !ccurs in
+ure red cell a+lasia ./CA& and immunemediated ine''ecti-e erythr!+!iesis, causes a
n!nregenerati-e anemia(10,11
Mature Erythrocytes
)he 'inal c!m+artment !' the /C mass is c!m+!sed !' mature erythr!cytes( Mature
erythr!cytes e*trude their nuclei and cell !rganelles be'!re being released int! the
bl!!dstream( Disease +r!cesses that alter this c!m+artment t! cause anemia are /C l!ss
internal !r e*ternal bleeding& and destructi!n hem!lysis&( In m!st cases, anemia due t! bl!!d
l!ss !r destructi!n is regenerati-e(
%ia&nostic -ests
)he initial e-aluati!n !' anemia reBuires '!ur diagn!stic tests: measurement !' the .CV !r
hemat!crit, Buanti'icati!n !' t!tal +lasma s!lids ) +lasma +r!tein and 'ibrin!gen&
c!ncentrati!n by re'ract!metry, e*aminati!n !' a bl!!d smear, and a c!m+lete bl!!d c!unt
CC&( )hree !' these tests can be +er'!rmed immediately by alm!st all +ractiti!ners and yield
a great deal !' in'!rmati!n( )he .CV and ) -alues are determined a'ter centri'ugati!n !' a
small Buantity !' bl!!d in micr!hemat!crit tubes( )he .CV identi'ies the +resence !' anemia
and all!s determinati!n !' se-erity( )he ) c!ncentrati!n may hel+ distinguish beteen bl!!d
l!ss and hem!lysis( =*aminati!n !' the serum in the micr!hemat!crit tube ill re-eal
hy+erbilirubinemia !r hem!gl!binemia, i' +resent( An alg!rithm '!r the diagn!sis !' anemia is
+resented in FIGURE .
The Blood Smear
l!!d smear e*aminati!n +r!-ides instantane!us in'!rmati!n ab!ut the nature !' the anemia
thr!ugh !bser-ati!n !' /C m!r+h!l!gy( Additi!nally, many erythr!cyte abn!rmalities that
cann!t be detected by !ther tests may be re-ealed !n a bl!!d smear( A 'e e*am+les are the+resence !' s+her!cytes, aut!agglutinati!n, 7ein8 b!dies, +!iil!cytes i(e(, abn!rmally
sha+ed erythr!cytes&, erythr!+arasites, and nucleated /Cs( +her!cytes a++ear smaller than
n!rmal /Cs and lac central +all!r( In d!gs, the +resence !' s+her!cytes and
aut!agglutinati!n suggests immunemediated hem!lytic anemia IM7A&(12 Identi'icati!n !'
s+her!cytes in cats is n!t +!ssible because n!rmal 'eline /Cs are smaller and dem!nstrate
less central +all!r than canine /Cs(1" 7ein8 b!dies are small, r!und +ieces !' denatured
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hem!gl!bin that !'ten +r!trude 'r!m the cell margin( =ccentr!cytes are /Cs in hich the
hem!gl!bin has shi'ted t! !ne side, lea-ing a clear 8!ne al!ng the !ther side( /u+tured
eccentr!cytes are called pyknocytes( 6ie s+her!cytes, +yn!cytes are smaller than n!rmal
/Cs, lac central +all!r, and may be di''icult t! a++reciate in cats( )he +resence !' 7ein8
b!dies, eccentr!cytes, and +yn!cytes indicates !*idati-e damage t! /Cs, such as !ccursith !ni!n, acetamin!+hen, 8inc, and !ther t!*ic!ses as ell as se-eral metab!lic diseases in
cats(1#41%
=chin!cytes, hich ha-e sh!rt, e-enly s+aced s+icules, are !'ten the result !' bl!!d drying
sl!ly !n the slide but are als! seen ith certain c!nditi!ns such as gl!merul!ne+hritis,
lym+h!sarc!ma, and rattlesnae en-en!mati!n(1>,1@ Acanth!cytes ha-e large, irregularly
s+aced +r!3ecti!ns and are m!st c!mm!nly ass!ciated ith hemangi!sarc!ma in d!gs and
he+atic li+id!sis in cats(1,20chist!cytes and erat!cytes are +ieces !' /Cs, the latter ith
s+icules( )hese cells indicate /C 'ragmentati!n, as is seen ith disseminated intra-ascular
c!agulati!n and hemangi!sarc!ma(21 $ucleated /Cs may be n!ted ith acceleratederythr!+!iesis !r may suggest s+lenic disease, b!ne marr! disease, !r lead +!is!ning(22
The Reticulocyte Count
/eticul!cytes are /Cs that ha-e been released 'r!m the b!ne marr! be'!re c!m+lete
e*trusi!n !' all /$A and cellular !rganelles( )hey can be dem!nstrated in a bl!!d smear using
su+ra-ital stains such as ne methylene blue !r brilliant cresyl blue( )hese stains +reci+itate
the /$A in the reticul!cyte, staining it blue( /eticul!cytes stained ith ne methylene blue
a++ear as erythr!cytes ith blue granules( /eticul!cytes are generally n!t !bser-ed '!r 2 t! #
days a'ter an acute e+is!de !' bl!!d l!ss !r hem!lysis( )he reticul!cyte res+!nse generally+eas beteen # and > days a'ter the insult and starts t! decline at 2 t! " ees in d!gs and
t! 1" days in cats, assuming the underlying cause !' the anemia has been treated(2",2#
)here are t! ty+es !' reticul!cytes: aggregate and +unctate( Aggregate reticul!cytes are
larger and less mature than +unctate reticul!cytes( Cats are uniBue in that their +unctate
reticul!cytes ha-e a l!ng hal'li'e in bl!!d and there'!re can re'lect an insult that !ccurred days
t! ees +ri!r t! testing(2",2# .unctate reticul!cytes d! n!t accumulate in large numbers in
d!gs( Aggregate reticul!cytes are c!nsidered an indicat!r !' current regenerati!n in b!th
s+ecies(
A reticul!cyte c!unt can be +er'!rmed by incubating a small am!unt !' =D)Aantic!agulated
bl!!d ith an eBual am!unt !' a su+ra-ital stain such as ne methylene blue '!r 10 minutes
be'!re maing a bl!!d smear slide( )he number !' reticul!cytes seen +er 1000 /Cs is then
c!unted( A high+!er 'ield #0E !b3ecti-e& in hich the /Cs are t!uching !r 3ust !-erla++ing
c!ntains a++r!*imately 200 cells( )he number !' reticul!cytes c!unted in 'i-e such 'ields is
di-ided by 10 t! yield the reticul!cyte +ercentage number !' reticul!cytes +er 100 /Cs&( In
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cats, aggregate reticul!cytes are di''erentiated 'r!m +unctate reticul!cytes by the +resence !'
clum+ed reticulum as !++!sed t! indi-idual +ieces !' reticulum( A c!rrected reticul!cyte c!unt
'!r the degree !' anemia is calculated by multi+lying the reticul!cyte +ercentage e*+ressed as
a +ercentage by the rati! !' the +atient
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In cases !' regenerati-e anemia ith an a++r!+riate marr! res+!nse t! increased
erythr!+!ietin le-els, /C +r!ducti!n is accelerated and results in the release !' reticul!cytes
int! the bl!!dstream(2" Changes in the /C indices ith regenerati-e anemia may include
macr!cyt!sis high MCV&, heter!gene!us cell -!lume high /DW&, and hy+!chr!masia l!
MC7C&( )he decreased MC7C re'lects a n!rmal hem!gl!bin c!ntent in a largerthann!rmalcell( n bl!!d smear e-aluati!n, /C m!r+h!l!gy sh!s -arying am!unts !' anis!cyt!sis
-ariati!n in -!lume& and macr!cyt!sis large cells& de+ending !n the degree !' regenerati!n
and underlying +r!cess( $ucleated /C metarubricytes !r late rubricytes& may als! be n!ted
ith accelerated erythr!+!iesis(
.!lychr!mat!+hils are immature /Cs that stain blue+ur+le !n Wrightstained bl!!d smears(
.!lychr!masia!n bl!!d smear e*aminati!n and reticul!cyt!sis are the hallmars !'
regenerati-e anemia(
)he reticul!cyte c!unt must be inter+reted in light !' the degree !' anemia( Minimal t! mild
reticul!cyt!sis in the +resence !' se-ere anemia is c!nsidered n!nregenerati-e i' su''icient
time '!r an adeBuate res+!nse has +assed( eBuential hem!grams and reticul!cyte c!unts are
instrumental in maing this determinati!n(
%ia&nostic %ifferentias
nce the regenerati-e status !' the anemia has been determined, m!re s+eci'ic tests are
indicated t! systematically eliminate the -ari!us causes !' each categ!ry !' anemia(
Nonregenerative Anemia
In m!st cases !' true n!nregenerati-e anemia i(e(, n!t hem!rrhage !r hem!lysis that has n!t
yet begun t! regenerate&, the anemia is mild t! m!derate(2% Causes !' n!nregenerati-e anemia
are listed in BOX ' . )he m!st c!mm!n cause !' n!nregenerati-e anemia in d!gs and cats is
in'lammat!ry disease( Anemia !' in'lammat!ry disease '!rmerly anemia of chronic disease&
can be a seBuela !' a multitude !' in'lammat!ry, in'ecti!us, traumatic, and ne!+lastic
diseases(2>4"0ther causes !' n!nregenerati-e anemia include chr!nic renal 'ailure,
hy+!thyr!idism in d!gs, and +rimary b!ne marr! disease("1 Certain causes !'
n!nregenerati-e anemia, such as Fe6V in'ecti!n, ./CA, and laterstage chr!nic renal 'ailure
erythr!+!ietin de'iciency&, may +resent ith a m!re se-ere anemia(CC and chemistry +r!'ile,
urinalysis, and th!racic and abd!minal imaging can hel+ identi'y the +resence !' underlying
disease, ne!+lasia, !r renal 'ailure( /etr!-iral testing is indicated '!r cats( )hyr!id testing may
be indicated '!r d!gs( I' n! underlying disease can be identi'ied, b!ne marr! e-aluati!n is
indicated t! hel+ identi'y c!nditi!ns such as ./CA, myel!dys+lasia, leuemia, and a+lastic
+ancyt!+enia(
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Regenerative Anemia
I' the anemia is determined t! be regenerati-e, the ne*t ste+ is t! di''erentiate bl!!d l!ss 'r!m
hem!lysis( As +re-i!usly stated, e-aluati!n !' the ) is !'ten hel+'ul( Decreased ) is m!re
c!nsistent ith bl!!d l!ss, hereas n!rmal t! increased ) is suggesti-e !' hem!lysis(
=le-ated ) in the 'ace !' anemia may suggest dehydrati!n !r hy+ergl!bulinemia(
Causes !' bl!!d l!ss are listed in BOX 0(
M!st causes !' bl!!d l!ss can be easily identi'ied( l!!d l!ss related t! trauma is sus+ected
based !n hist!ry( .hysical e*aminati!n and imaging !' the th!ra* and abd!men can identi'y
the +resence !' intraca-itary hem!rrhage in cases !' trauma, tum!r ru+ture, !r a bleeding
diathesis( /ec!-ery !' n!ncl!tting bl!!d !n abd!min!centesis indicates the +resence !'
hem!abd!men( /esults !' a +latelet c!unt and cl!tting +r!'ile are used t! eliminate a bleeding
diathesis( 9astr!intestinal 9I& bleeding may be indicated by the +resence !' hematemesis !r
melena !r may be !ccult and di''icult t! c!n'irm( )ests that may be used in cases !' sus+ected
9I bleeding include 'ecal analysis, abd!minal imaging, and end!sc!+y( As discussed earlier,
chr!nic bleeding may e-entually lead t! ir!n de'iciency and, subseBuently, micr!cytic,
hy+!chr!mic, heter!gene!us anemia(
BOX 0. Causes of Bood 2oss
Interna or e3terna
• C!agulati!n !r +latelet dis!rders antic!agulant r!denticide t!*ic!sis, disseminated
intra-ascular c!agulati!n, c!ngenital 'act!r de'iciency, thr!mb!cyt!+enia, -!n
Willebrand disease&
• )rauma
• urgery
Interna
• +lenic ru+ture hemat!ma, ne!+lasia, trauma&
• 7em!rrhage 'r!m n!ns+lenic ne!+lasms
E3terna
• Chr!nic bleeding9I ne!+lasia, +!ly+, ulcers, h!!!rms, in'lammat!ry b!el
disease&, res+irat!ry, ur!genital
• =ct!+arasites usually 3u-enile +atients&'leas, tics
In cases !' regenerati-e anemia, hem!lysis bec!mes the m!st liely disease +r!cess i' bl!!d
l!ss is ruled !ut( Causes !' hem!lysis are listed in BOX ) . 7em!lysis can be immune
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mediated !r n!n4immune mediated( )he m!st c!mm!n cause !' hem!lysis in small animals is
IM7A("2 IM7A can be +rimary !r sec!ndary t! !ther diseases e(g(, in'ecti!us disease,
ne!+lasia&, drug ad-erse e''ects, !r -accine ad-erse reacti!ns(12,""4"> )he +rimary '!rm may
als! be termed idiopathic !r autoimmune hemolytic anemia A#$A&( )he diagn!sis !' IM7A is
su++!rted by a l! hemat!crit ty+ically K25L& ith !ne !r m!re !' the '!ll!ing:aut!agglutinati!n, +!siti-e C!!mbs test result, s+her!cyt!sis in d!gs&, and increased !sm!tic
'ragility("@," )he +resence !' n!n4immunemediated hem!lysis may be suggested by the
hist!ry e(g(, ingesti!n !' !ni!ns, en-en!mati!n&, by breed e(g(, +h!s+h!'ruct!inase !r
+yru-ate inase de'iciency&, by the +resence !' underlying disease e(g(, micr!angi!+athic
trauma due t! hemangi!sarc!ma&, !r by 'indings !n imaging e(g(, 8inc t!*ic!sis&(
7em!lysis can als! be classi'ied as intra-ascular, e*tra-ascular, !r a c!mbinati!n !' b!th(
=*aminati!n !' serum and urine can s!metimes aid in this determinati!n( Intra-ascular
hem!lysis results in the release !' hem!gl!bin int! the bl!!d that is then 'iltered int! the urine,
causing the serum and urine t! de-el!+ a dar red c!l!r( )he di''erential diagn!sis '!r dar red
urine includes hematuria, hem!gl!binuria, and my!gl!binuria( 7ematuria can be di''erentiated
'r!m hem!gl!binuria and my!gl!binuria by centri'ugati!n !' the urine( With hematuria, the
/Cs ill '!rm a +ellet and the su+ernatant ill clear a'ter centri'ugati!n, hereas ith
hem!gl!binuria and my!gl!binuria, the su+ernatant ill remain +igmented( 7em!gl!binuria
can be di''erentiated 'r!m my!gl!binuria by analysis !' serum '!r creatine inase acti-ity, hich
is ty+ically increased in cases !' my!gl!binuria( )he +resence !' hem!gl!binemia and
hem!gl!binuria in the setting !' regenerati-e anemia is the hallmar !' intra-ascular
hem!lysis(1" Causes !' intra-ascular hem!lysis include IgMmediated IM7A, 8inc t!*ic!sis,
+h!s+h!'ruct!inase de'iciency, and s!me cases !' !*idati-e damage such as !ccurs ith
!ni!n ingesti!n(1",#04#2
=*tra-ascular hem!lysis, and t! s!me degree intra-ascular hem!lysis, results in the release !'
increased am!unts !' bilirubin int! the bl!!d( As a''ected /Cs are +hag!cyt!sed by the
m!n!nuclear+hag!cyte system in the s+leen and li-er, hem!gl!bin in the /Cs is
metab!li8ed and aterins!luble unc!n3ugated& bilirubin is released int! +lasma, here it
binds t! albumin( ?nc!n3ugated bilirubin is taen u+ by he+at!cytes '!r c!n3ugati!n int! a
aters!luble c!n3ugated& '!rm '!r e*creti!n in bile( Massi-e hem!gl!bin bread!n,
es+ecially in the setting !' c!ncurrent he+atic in3ury 'r!m hy+!*ia, in'lammati!n, !r thr!mb!sis,
can lead t! bac'l! !' c!n3ugated and unc!n3ugated bilirubin int! the +lasma( C!n3ugated
bilirubin is e*creted int! urine by the idneys, !'ten leading t! a dar yell! urine( A small
am!unt !' bilirubinuria can be n!rmal in d!gs due t! the ability !' the canine idney t!
c!n3ugate bilirubin( ilirubinuria in cats is alays abn!rmal( )he di''erential diagn!sis !'
bilirubinuria and hy+erbilirubinemia includes causes !' he+atic dys'uncti!n and biliary
!bstructi!n( $!t all cases !' e*tra-ascular hem!lysis dem!nstrate bilirubinuria and
hy+erbilirubinemia due t! the li-er
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An easy but crude inh!use test t! identi'y agglutinati!n caused by IM7A is the saline
dis+ersi!n test( F!r this test, clum+s !' /Cs must 'irst be seen !n a glass slide c!ntaining !ne
dr!+ !' h!le !r =D)Aantic!agulated bl!!d and 2 t! 5 dr!+s !' saline s!luti!n( )! di''erentiate
r!uleau* /Cs adhered in chains !r stacs& 'r!m agglutinati!n, a c!-ersli+ is +laced !-er a
dr!+ !' =D)Aantic!agulated bl!!d !n a ne slide, and se-eral dr!+s !' saline s!luti!n are+laced al!ng the edge !' the c!-ersli+( )he /Cs are !bser-ed thr!ugh a micr!sc!+e t! see
hether clum+s dis+erse !r +ersist hen the saline s!luti!n rushes in( .ersistent agglutinati!n
indicates the +resence !' anti/C immun!gl!bulin !n the sur'ace !' /Cs and su++!rts a
diagn!sis !' IM7A( It d!es n!t indicate hether the IM7A is +rimaryaut!immune !r sec!ndary(
As this is a crude test, results sh!uld be c!nsidered as su++!rti-e !nly(
In d!gs, the m!st c!mm!n cause !' s+her!cyt!sis is immunemediated hem!lysis as the
immun!gl!bulinc!-ered /C membranes are attaced by macr!+hages in the li-er and
s+leen( 6ess c!mm!n reas!ns '!r the +resence !' s+her!cytes include n!n4immunemediated
causes !' hem!lysis such as micr!angi!+athic trauma, 8inc t!*ic!sis, and trans'usi!n !' st!redbl!!d(1",#0+her!cytes can als! be seen ith se-ere snaebite and beesting
en-en!mati!n(#",##
)he direct antigl!bulin !r C!!mbs test identi'ies the +resence !' immun!gl!bulin !r
c!m+lement !n the sur'ace !' /Cs(#5,#% A +!siti-e result su++!rts IM7A but d!es n!t
distinguish hether it is +rimary !r sec!ndary( Falsenegati-e and, less c!mm!nly, 'alse
+!siti-e results can !ccur( )he utility !' a C!!mbs test in cats has hist!rically been c!nsidered
dubi!us, but results !' a 200% study dem!nstrated reas!nable sensiti-ity and s+eci'icity '!r the
diagn!sis !' IM7A in cats("5
In d!gs, IM7A is usually +rimary !r idi!+athic("2,",#> )he diagn!sis !' +rimaryaut!immune
IM7A is !ne !' e*clusi!n thus, !nce IM7A has been diagn!sed and an ass!ciati!n ith a drug
ad-erse e''ect !r -accine ad-erse reacti!n has been eliminated, tests t! rule !ut an underlying
ne!+lastic !r in'ecti!us disease are indicated, es+ecially in !lder +atients( Cats ha-e l!ng been
c!nsidered m!re liely t! ha-e sec!ndary IM7A,1","%,">,#@ but +rimary IM7A is being rec!gni8ed
m!re 'reBuently in this s+ecies("5 It is im+!rtant t! rule !ut Fe6V in'ecti!n, FIV in'ecti!n, and
hem!tr!+ic myc!+lasm!sis '!rmerly $emobartonella in'ecti!n& in cats ith IM7A and t!
c!nsider 'eline in'ecti!us +erit!nitis, ehrlichi!sis, ana+lasm!sis, drug e''ects, and ne!+lasia
hen a++r!+riate(1","%,">,#>,#,50
Concusion
)he many causes !' anemia in cats and d!gs can mae the r!ad t! a diagn!sis seem
daunting( 7!e-er, a systematic a++r!ach m!st !'ten yields the c!rrect diagn!sis( In'!rmati!n
ra+idly deri-ed at initial e-aluati!n .CV) and bl!!d 'ilm e*aminati!n& can be used al!ng
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ith data 'r!m an aut!mated CC erythr!cyte c!unt and indices& '!r this +ur+!se( Additi!nal
tests, including reticul!cyte c!unt, seBuential bl!!d smear e*aminati!ns, C!!mbs test, and
saline dis+ersi!n, !'ten hel+ t! 'urther characteri8e the anemia(
)his article as m!di'ied by the rem!-al !' a table 'r!m !* 2 !n January @, 201"(
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