Anemia: Determining Determining the Cause by Wendy Fleischman, DVM, DACVIM
June 2012 V!l "#, $! %&
Abstract Anemia is a common finding in small animal practice; however, however, the multitude of potential causes can make determining the underlying diagnosis a challenging and frustrating endeavor. With a basic understanding of red blood cell production and a systematic diagnostic approach, clinicians should be able to clearly define the cause of anemia in most cases. Anemia re'ers t! a reduced hem!gl!bin hem!gl!bin c!ncentrati!n due t! decreased red red bl!!d cell mass( )his can be e*+ressed as a +aced cell -!lume .CV&, hemat!crit, red bl!!d cell /C& c!unt, !r hem!gl!bin le-el bel! the re'erence inter-al( F!r sim+licity, hemat!crit !r .CV ill be used in this article(
Erythropoiesis and Erythrokinetics A basic basic gras+ !' /C +r!ducti!n can c!ntribute much t! understanding understanding the causes !' anemia( In adult mammals, /Cs are +r!duced +rimarily in the b!ne marr!(1 )he /C mass can be di-ided int! '!ur +hases !r c!m+artments: stem cells, +r!genit!r cells, +recurs!r cells, and mature erythr!cytes( 2 A diagram illustrating the de-el!+ment !' /Cs is +r!-ided in FIGURE 1 . Stem Cells )he hem!+!ietic stem cells are a small +!+ulati!n !' unc!mmitted, sel'reneing germ cells( )hese cells can gi-e rise t! all ty+es !' bl!!d cells erythr!cytes, leu!cytes, and +latelets&( In3ury t! the stem cell c!m+artment is an unc!mm!n cause !' anemia( In such a situati!n, the anemia is acc!m+anied by de'iciencies in the !ther t! cell lines, a c!nditi!n re'erred t! as aplastic anemia, anemia, !r, m!re c!rrectly, aplastic pancytopenia( pancytopenia( /e+!rted causes !' a+lastic +ancyt!+enia are listed inBOX inBOX 1( 1("45 BOX 1. Reported Causes of Apastic Ane!ia Ane!ia "Apastic #ancytopenia$ in %o&s and Cats'() Infectious a&ents •
.ar-!-irus
•
•
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! renal hy+!*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
.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! d ys'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 !' a nemia 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 !' a nemia 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
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 !ccurs ith !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 $ucleated /Cs may be n!ted ith accelerated erythr!+!iesis !r may suggest s+lenic disease, b!ne marr! disease, !r lead +!is!ning( 22 The Reticulocyte Count /eticul!cytes are /Cs that ha-e been released 'r!m the b!ne marr! be'!re c!m+lete e*trusi!n !' all /$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 h as 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 sli de( )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
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
Cassification of Ane!ia by Re&eneratie /tatus )he initial ste+ in elucidating the cause !' anemia is t! determine hether the anemia is regenerati-e !r n!nregenerati-e( /egenerati-e anemia indicates that the b!ne marr! is able t! res+!nd t! the anemia a++r!+riately and that the liely cause !' anemia is bl!!d l!ss !r hem!lysis( $!nregenerati-e anemia indicates b!ne marr! dys'uncti!n and suggests a lac !' erythr!+!ietin, an inability !' the +r!genit!r cells t! res+!nd t! erythr!+!ietin, !r a maturati!n de'ect !' the +recurs!r cells( An acute case !' anemia due t! bl!!d l!ss !r hem!lysis may als! a++ear n!nregenerati-e '!r the 'irst 'e days( )he bl!!d smear e*aminati!n and /C +arameters 'r!m the CC +r!-ide a g!!d '!undati!n t! begin e-aluati!n '!r the +resence !' regenerati!n( 2",25 $!nregenerati-e anemia is m!st c!mm!nly n!rm!cytic n!rmal mean cell -!lume GMCVH&, n!rm!chr!mic n!rmal mean cell hem!gl!bin c!ncentrati!n GMC7CH&, and h!m!gene!us in cell -!lume n!rmal /C distributi!n idth G/DWH&( /C m!r+h!l!gy is ty+ically n!rmal !n a bl!!d smear( 6ess c!mm!nly, n!nregenerati-e anemia is micr!cytic l! MCV&, hy+!chr!mic l! MC7C&, and heter!gene!us in cell -!lume increased /DW&( )his situati!n is m!st c!mm!nly seen ith anemia due t! se-ere ir!n de'iciency, a seBuela !' chr!nic bl!!d l!ss( /DW is an inde* !' the -ariati!n in /C -!lume( An increase in /DW indicates heter!geneity in /C si8e -!lume&( )his can be due t! an increase in small cells, an increase in large cells, !r b!th(
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!rmal cell( 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& d e+ending !n the degree !' re generati!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( Mini mal 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 h as 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 a nemia 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(
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 b y 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
mediated !r n!n4immune mediated( )he m!st c!mm!n cause !' hem!l ysis 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 !' he m!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
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 i mmunemediated hem!lysis as the immun!gl!bulinc!-ered /C membranes are attaced by macr!+hages in the l i-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!red bl!!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
ith data 'r!m an aut!mated CC erythr!cyte c!unt and i ndices& '!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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