hLLp//wwwmayocllnlccom/healLh/aplasLlcanemla/uS00322/uSLC1lCnsympLoms

0ef|n|t|on
8y Vayo C||r|c slall
Ap|asl|c arer|a |s a cord|l|or lral occurs Wrer your oody slops produc|rg erougr reW o|ood ce||s.
Ap|asl|c arer|a |eaves you lee||rg lal|gued ard al r|grer r|s| ol |rlecl|ors ard urcorlro||ed o|eed|rg.
A rare ard ser|ous cord|l|or, ap|asl|c arer|a car deve|op al ary age. Ap|asl|c arer|a ray occur
sudder|y, or |l car occur s|oW|y ard gel Worse over a |org per|od ol l|re. Trealrerl lor ap|asl|c arer|a
ray |rc|ude red|cal|ors, o|ood lrarslus|ors or a sler ce|| lrarsp|arl.
8ymptoms
8y Vayo C||r|c slall
Ap|asl|c arer|a syrplors resu|l lror a srorlage ol ore or rore lypes ol o|ood ce||s. 3|grs ard syrplors
ray |rc|ude:
O al|gue
O 3rorlress ol orealr W|lr exerl|or
O #ap|d or |rregu|ar rearl rale
O !a|e s||r
O requerl or pro|orged |rlecl|ors
O &rexp|a|red or easy oru|s|rg
O oseo|eeds ard o|eed|rg gurs
O !ro|orged o|eed|rg lror culs
O 3||r rasr
O |zz|ress
O eadacre
Ap|asl|c arer|a car progress s|oW|y over Wee|s or rorlrs, or |l ray core or sudder|y. Tre |||ress ray
oe or|el, or |l ray oecore crror|c. Ap|asl|c arer|a car oe very severe ard ever lala|.
,:ses
8y Vayo C||r|c slall
Ap|asl|c arer|a deve|ops Wrer darage occurs lo your oore rarroW, s|oW|rg or srull|rg doWr lre
producl|or ol reW o|ood ce||s. 8ore rarroW |s a red, sporgy raler|a| |rs|de your oores lral produces sler
ce||s, Wr|cr g|ve r|se lo olrer ce||s. 3ler ce||s |r lre oore rarroW produce o|ood ce||s red ce||s, Wr|le
ce||s ard p|ale|els. lr ap|asl|c arer|a, lre oore rarroW |s descr|oed |r red|ca| lerrs as ap|asl|c or
rypop|asl|c rear|rg lral |l's erply (ap|asl|c) or corla|rs very leW o|ood ce||s (rypop|asl|c).
aclors lral car lerporar||y or perrarerl|y |rjure oore rarroW ard allecl o|ood ce|| producl|or |rc|ude:
O #,/|,t|on ,n/ chemother,py tre,tments. wr||e lrese carcer-l|grl|rg lrerap|es |||| carcer ce||s, lrey car
a|so darage rea|lry ce||s, |rc|ud|rg sler ce||s |r oore rarroW. Ap|asl|c arer|a car oe a lerporary s|de
ellecl ol lrese lrealrerls.
O pos:re to to|c chem|c,s. Exposure lo lox|c crer|ca|s, sucr as sore used |r pesl|c|des ard
|rsecl|c|des, ray cause ap|asl|c arer|a. Exposure lo oerzere ar |rgred|erl |r gaso||re a|so ras
oeer ||r|ed lo ap|asl|c arer|a. Tr|s lype ol arer|a sorel|res gels oeller or |ls oWr |l you avo|d repealed
exposure lo lre crer|ca|s lral caused your |r|l|a| |||ress.
O &se of cert,|n /r:s. 3ore red|cal|ors, sucr as lrose used lo lreal rreuralo|d arlrr|l|s ard sore
arl|o|ol|cs, car cause ap|asl|c arer|a.
O :to|mm:ne /|sor/ers. Ar aulo|rrure d|sorder, |r Wr|cr your |rrure sysler oeg|rs allac||rg rea|lry
ce||s, ray |rvo|ve sler ce||s |r your oore rarroW.
O v|r, |nfect|on. v|ra| |rlecl|ors lral allecl oore rarroW ray p|ay a ro|e |r lre deve|oprerl ol ap|asl|c
arer|a |r sore peop|e. v|ruses lral rave oeer ||r|ed lo lre deve|oprerl ol ap|asl|c arer|a |rc|ude
repal|l|s, Epsle|r-8arr, cylorega|ov|rus, parvov|rus 819 ard lv.
O !ren,ncy. Ap|asl|c arer|a lral occurs |r pregrarcy ray oe re|aled lo ar aulo|rrure proo|er your
|rrure sysler ray allac| your oore rarroW dur|rg pregrarcy.
O &nknown f,ctors. lr rary cases, doclors arer'l ao|e lo |derl|ly lre cause ol ap|asl|c arer|a. Tr|s |s
ca||ed |d|opalr|c ap|asl|c arer|a.
onf:s|on w|th myeo/ysp,st|c syn/rome
Ap|asl|c arer|a car oe r|sla|er lor a cord|l|or ca||ed rye|odysp|asl|c syrdrore. lr lr|s group ol
d|sorders, lre oore rarroW produces reW o|ood ce||s, oul lrey're delorred ard urderdeve|oped. Tre oore
rarroW |r rye|odysp|asl|c syrdrore |s sorel|res ca||ed ryperp|asl|c rear|rg lral |l's pac|ed W|lr
o|ood ce||s. 8ul sore peop|e W|lr rye|odysp|asl|c syrdrore rave erply rarroW lral's d|ll|cu|l lo
d|sl|rgu|sr lror ap|asl|c arer|a.
onnect|ons w|th other r,re /|sor/ers
3ore peop|e W|lr ap|asl|c arer|a a|so rave a rare d|sorder |roWr as paroxysra| roclurra|
rerog|oo|rur|a. Tr|s d|sorder causes red o|ood ce||s lo orea| doWr loo soor. !aroxysra| roclurra|
rerog|oo|rur|a car |ead lo ap|asl|c arer|a, or ap|asl|c arer|a car evo|ve |rlo paroxysra| roclurra|
rerog|oo|rur|a.
arcor|'s arer|a |s a rare, |rrer|led d|sease lral |eads lo ap|asl|c arer|a. Cr||drer oorr W|lr |l lerd lo oe
sra||er lrar average ard rave o|rlr delecls, sucr as urderdeve|oped ||ros. Tre d|sease |s d|agrosed W|lr
lre re|p ol o|ood lesls.
#|sk f,ctors
8y Vayo C||r|c slall
Ap|asl|c arer|a |s rare. aclors lral ray |rcrease your r|s| |rc|ude:
O Trealrerl W|lr r|gr-dose rad|al|or or crerolrerapy lor carcer
O Exposure lo lox|c crer|ca|s
O Tre use ol sore prescr|pl|or drugs sucr as cr|orarprer|co|, Wr|cr |s used lo lreal oacler|a| |rlecl|ors,
ard go|d corpourds used lo lreal rreuralo|d arlrr|l|s
O Cerla|r o|ood d|seases, aulo|rrure d|sorders ard ser|ous |rlecl|ors
O !regrarcy, rare|y
!rep,r|n for yo:r ,ppo|ntment
8y Vayo C||r|c slall
ll you rave s|grs or syrplors ol ap|asl|c arer|a, slarl oy ra||rg ar appo|rlrerl W|lr your lar||y doclor
or a gerera| pracl|l|orer. ll you're doclor suspecls ap|asl|c arer|a, you'|| |||e|y oe relerred lo a doclor Wro
spec|a||zes |r lreal|rg o|ood d|sorders (reralo|og|sl). ll ap|asl|c arer|a cores or sudder|y, you ray
oeg|r lrealrerl |r lre erergercy roor.
ere's sore |rlorral|or lo re|p you gel ready lor your appo|rlrerl, ard Wral lo expecl lror your doclor.
h,t yo: c,n /o
O r|te /own ,ny symptoms yo:re eper|enc|n |rc|ud|rg ary lral ray seer urre|aled lo lre reasor
lor Wr|cr you scredu|ed lre appo|rlrerl.
O r|te /own key person, |nform,t|on |rc|ud|rg ary recerl ||le crarges, sucr as a reW joo, parl|cu|ar|y
ore lral exposes you lo crer|ca|s.
O ,ke , |st of , me/|c,t|ons as We|| as ary v|lar|rs or supp|ererls, lral you're la||rg.
O sk , f,m|y member or , fr|en/ to st,y w|th yo: Wr||e you la|| lo your doclor. You ray oe l|red or
overWre|red oy a|| lre |rlorral|or. A lr|erd or a lar||y reroer car la|e roles lor you, or or|rg up
quesl|ors you ray lorgel lo as|.
O r|te /own q:est|ons yo: w,nt to ,sk your doclor.
!repar|rg a ||sl ol quesl|ors aread ol l|re car re|p you ra|e lre rosl ol your l|re logelrer. or ap|asl|c
arer|a, sore oas|c quesl|ors lo as| your doclor |rc|ude:
O wral's lre rosl |||e|y cause ol ry syrplors?
O Are lrere olrer poss|o|e causes lor ry syrplors?
O wral's ry progros|s?
O wral lrealrerls are ava||ao|e, ard Wr|cr do you recorrerd?
O Are lrere ary a|lerral|ves lo lre pr|rary approacr lral you're suggesl|rg?
O l rave arolrer rea|lr cord|l|or. oW car l oesl rarage lrer logelrer?
O Are lrere ary orocrures or olrer pr|rled raler|a| lral l car la|e W|lr re? wral Weos|les do you
recorrerd?
lr add|l|or lo lre quesl|ors lral you've prepared lo as| your doclor, dor'l res|lale lo as| quesl|ors dur|rg
your appo|rlrerl.
h,t to epect from yo:r /octor
Your doclor |s |||e|y lo as| you a ruroer ol quesl|ors, sucr as:
O ave you rad ary |rlecl|ors?
O ave you rad ary urexpecled o|eed|rg?
O ave you le|l rore l|red lrar usua|?
O wrer d|d you oeg|r exper|erc|rg syrplors?
O ls lrere arylr|rg reW |r your ||le, sucr as a reW joo or a reW red|cal|or?
O oes arylr|rg seer lo |rprove your syrplors?
O oes arylr|rg appear lo Worser your syrplors?
O %ests ,n/ /|,nos|s
O 8y Vayo C||r|c slall
To d|agrose ap|asl|c arer|a, your doclor ray recorrerd:
O oo/ tests. orra||y, red o|ood ce||, Wr|le o|ood ce|| ard p|ale|el |eve|s slay W|lr|r a cerla|r rarge. Your
doclor ray suspecl ap|asl|c arer|a Wrer a|| lrree ol lrese o|ood ce|| |eve|s are very |oW.
O one m,rrow b|opsy. To corl|rr a d|agros|s, you'|| reed lo urdergo a oore rarroW o|opsy. lr lr|s
procedure, a doclor uses a reed|e lo rerove a sra|| sarp|e ol oore rarroW lror a |arge oore |r your
oody, sucr as your r|poore. Tre oore rarroW sarp|e |s exar|red urder a r|croscope lo ru|e oul olrer
o|ood-re|aled d|seases. lr ap|asl|c arer|a, oore rarroW corla|rs leWer o|ood ce||s lrar rorra|.
0rce you've rece|ved a d|agros|s ol ap|asl|c arer|a, you ray reed add|l|ora| lesls lo delerr|re ar
urder|y|rg cause.
r|rg corp||cal|ors. lr add|l|or, rol everyore |s a card|dale lor lrarsp|arlal|or or car l|rd a su|lao|e doror.
|mm:nos:ppress,nts
or peop|e Wro car'l urdergo a oore rarroW lrarsp|arl or lor lrose Wrose ap|asl|c arer|a ray oe due lo
ar aulo|rrure d|sorder, lrealrerl ray |rvo|ve drugs lral a|ler or suppress lre |rrure sysler
(|rrurosuppressarls).
rugs sucr as cyc|ospor|re (0ergral, eora|, 3ard|rrure) ard arl|-lryrocyle g|oou||r (Tryrog|oou||r)
are exarp|es. Trese drugs suppress lre acl|v|ly ol |rrure ce||s lral are darag|rg your oore rarroW.
Tr|s re|ps your oore rarroW recover ard gererale reW o|ood ce||s. Cyc|ospor|re ard arl|-lryrocyle
g|oou||r are oller used |r coro|ral|or.
Corl|coslero|ds, sucr as relry|predr|so|ore (Vedro|, 3o|u-Vedro|), are oller g|ver al lre sare l|re as
lrese drugs.
lrrure-suppress|rg drugs car oe very ellecl|ve al lreal|rg ap|asl|c arer|a. Tre doWrs|de |s lral lrese
drugs lurlrer Wea|er your |rrure sysler. ll's a|so poss|o|e lral aller you slop la||rg lrese drugs, ap|asl|c
arer|a ray relurr.
one m,rrow st|m:,nts
Cerla|r drugs |rc|ud|rg co|ory-sl|ru|al|rg laclors, sucr as sargrarosl|r (Leu||re), l||grasl|r
(eupoger) ard pegl||grasl|r (eu|asla), ard epoel|r a|la (Epoger, !rocr|l) ray re|p sl|ru|ale lre
oore rarroW lo produce reW o|ood ce||s. 0roWlr laclors are oller used |r coro|ral|or W|lr |rrure-
suppress|rg drugs.
nt|b|ot|cs ,nt|v|r,s av|rg ap|asl|c arer|a Wea|ers your |rrure sysler. You rave leWer Wr|le o|ood
ce||s |r c|rcu|al|or lo l|grl oll gerrs. Tr|s |eaves you suscepl|o|e lo |rlecl|ors.
Al lre l|rsl s|gr ol |rlecl|or, sucr as a lever, see your doclor. You dor'l Warl lre |rlecl|or lo gel Worse,
oecause |l cou|d prove ||le-lrrealer|rg. ll you rave severe ap|asl|c arer|a, your doclor ray g|ve you
arl|o|ol|cs or arl|v|ra| red|cal|ors lo re|p preverl |rlecl|ors.
0ther tre,tments
Ap|asl|c arer|a caused oy rad|al|or ard crerolrerapy lrealrerls lor carcer usua||y |rproves orce you
corp|ele lrose lrealrerls. Tre sare |s lrue lor rosl olrer drugs lral |rduce ap|asl|c arer|a.
!regrarl Worer W|lr ap|asl|c arer|a are lrealed W|lr o|ood lrarslus|ors. or rary Worer, pregrarcy-
re|aled ap|asl|c arer|a |rproves orce lre pregrarcy erds. ll lral doesr'l rapper, lrealrerl |s sl|||
recessary.
L|festye ,n/ home reme/|es
8y Vayo C||r|c slall
ll you rave ap|asl|c arer|a, la|e care ol yourse|l oy:
O #est|n when yo: nee/ to. Arer|a car cause lal|gue ard srorlress ol orealr W|lr ever r||d exerl|or.
Ta|e a orea| ard resl Wrer you reed lo.
O vo|/|n cont,ct sports. 8ecause ol lre r|s| ol o|eed|rg assoc|aled W|lr a |oW p|ale|el courl, avo|d
acl|v|l|es lral ray resu|l |r a cul or la||.
O !rotect|n yo:rsef from erms. You car reduce your r|s| ol |rlecl|ors W|lr lrequerl rard-Wasr|rg ard
oy avo|d|rg s|c| peop|e. ll you deve|op a lever or olrer |rd|calors ol ar |rlecl|or, see your doclor lor
lrealrerl.
op|n ,n/ s:pport
8y Vayo C||r|c slall
T|ps lo re|p you ard your lar||y oeller cope W|lr your |||ress |rc|ude:
O #ese,rch yo:r /|se,se. Tre rore you |roW, lre oeller prepared you'|| oe lo ra|e lrealrerl dec|s|ors.
O sk q:est|ons. 8e sure lo as| your doclor aooul arylr|rg re|aled lo your d|sease or lrealrerl lral you
dor'l urderslard. ll ray re|p you lo record or Wr|le doWr Wral your doclor le||s you.
O e voc,. or'l oe alra|d lo express ary corcerrs you rave lo your doclor or ary olrer rea|lr care
proless|ora| lreal|rg you.
O 8eek s:pport. As| lar||y ard lr|erds lor erol|ora| supporl. As| lrer lo cors|der oecor|rg o|ood dorors
or oore rarroW dorors. Cors|der jo|r|rg ar ap|asl|c arer|a supporl group. ll ray oe re|plu| lo la|| lo
olrers cop|rg W|lr lre d|sease. As| your doclor |l re or sre |roWs ol ary |oca| supporl groups, or corlacl
lre Ap|asl|c Arer|a & V3 lrlerral|ora| ourdal|or. ll ollers a peer supporl relWor| ard car oe reacred
al 800-Z1Z-2820 .
O %,ke c,re of yo:rsef. !roper rulr|l|or ard s|eep are |rporlarl lo opl|r|ze o|ood producl|or.
O !revent|on
O 8y Vayo C||r|c slall
O Trere's ro preverl|or lor rosl cases ol ap|asl|c arer|a. oWever, avo|d|rg exposure lo
|rsecl|c|des, rero|c|des, orgar|c so|verls, pa|rl rerovers ard olrer lox|c crer|ca|s ray |oWer your
r|s| ol lre d|sease.

hLLp//wwwuLhLmcedu/paLhology/medlc/aplasLlcanemlahLml
Aplastic anemia is a hematologic disorder characterized by a decrease in the
cellular elements of the peripheral blood. This results from underproduction
of peripheral blood elements due to bone marrow failure. Aplastic anemia
develops before age 30-40 in patients who are predisposed due to a
congenital chromosomal abnormality such as Fanconi's anemia or
dyskeratosis congenita. Acquired aplastic anemia may be caused by toxic
chemicals, radiation, or by idiosyncratic reactions to medications or
infections. However, in over 50% of cases there is no identifiable cause and
the condition is then referred to as idiopathic aplastic anemia.
Making the Diagnosis
!atients with aplastic anemia generally present with symptoms of bleeding or bruising
due to the thrombocytopenia (low platelets), tiredness or pallor due to the anemia (low
hemoglobin), or infection due to the neutropenia (low white blood cell count). A
complete blood count and reticulocyte count usually show depression of all blood
elements (pancytopenia). The peripheral blood smear shows no abnormal cells. The
diagnosis is confirmed by a bone marrow biopsy with an assessment of cellularity. The
bone marrow is also evaluated for the degree of maturation of all cell lines.
Aplastic anemia is usually categorized as severe if, in addition to a hypocellular bone
marrow for age, two of the three following criteria are present: a platelet count of less
than 20,000/mm3, a corrected reticulocyte count of less than 1%, and a granulocyte or
absolute neutrophil count [ANC = total white count x (segs + bands)] of less than
500/mm3. !atients With pancytopenia, but not severe enough to meet the above
criteria, have mild or moderate aplastic anemia. Very severe aplastic anemia exists if
the ANC or granulocyte count is less than 200/mm3.
When aplastic anemia is diagnosed, all drugs or medications the patient is on should be
stopped if possible. Tests to exclude specific causes of aplastic anemia should be done
including a sugar water or a Ham test to rule out paroxysmal nocturnal hemoglobinuria
(!NH), B12 and folate levels and Hepatitis A, B, and C serologies. Bone marrow
chromosomes should be done to rule out a cytogenetic abnormality that may suggest a
diagnosis of myelodysplastic syndrome. !eripheral chromosome analysis using
diepoxybutane or mitomycin C should be done to rule out Fanconi's anemia in patients
under 40 years of age. !atients who are under 55 years of age and their siblings and
parents, if available, should be HLA typed at diagnosis to see if a bone marrow
transplant is a therapeutic option.
Treatment
!atients with mild or moderate aplastic anemia generally do not require immediate
treatment. Indeed, it is not known if they would benefit from early use of any of the
therapies described below. They should be watched carefully for any decline in their
blood counts. If such patients require transfusions, a decision should be made whether
any of the below therapies should be employed even though they do not meet strict
criteria for severe aplastic anemia.
For the patient with severe aplastic anemia, treatment should begin within 4 weeks
after presentation. Spontaneous increase in blood counts after 2-3 weeks is less likely
and potential for mortality and morbidity increase rapidly. Three types of therapy are
known to have benefit. These are bone marrow transplantation, immunosuppression
with medicines such as antithymocyte globulin (ATG) and/or cyclosporine, and
hematopoietic growth factors such as granulocyte colony stimulating factors (G-CSF),
granulocyte monocyte colony stimulating factor (GM-CSF), or other cytokines.
A bone marrow transplant is the treatment of choice for patients with severe or very
severe aplastic anemia less than 55-65 years of age in good medical condition who
have an HLA identical family member. In this procedure the patient is given toxic doses
of chemo- and/or radiotherapy and then infused with bone marrow from their HLA
identical donor. If there is no family member, a search of the unrelated bone marrow
transplant donor registries should be initiated even though the patient will initially be
treated with another modality. A bone marrow transplant center should be contacted to
provide further information and to discuss specific patient needs prior to referral.
The mainstay of initial therapy for the patient without HLA identical sibling donor is
immunosuppression. ATG, and anti-T cell agent, is given intravenously over 4 to 10
days according to various inpatient protocols. This medicine frequently results in high
fevers, moderate patient discomfort during its administration, and may transiently
increase transfusion requirements. More recently, ATG is being given in combination
with cyclosporine-A, an oral anti-T cell agent, and sometimes with prednisone as well.
The combination of medicines seems to result in a higher frequently of clinical response
than any of the medications given alone. However, even in patients who respond to
these agents blood cell production, although usually adequate to maintain a reasonable
quality of life, frequently is not normal even many years later.
More recently, therapy has been attempted with bioengineered molecules that increase
the production of blood cell elements. All of these medications are administered either
subcutaneously or intravenously and usually must be continued indefinitely once a
response is obtained. G- and GM-CSF stimulate the white blood cells and in a few cases
with prolonged use have resulted in small increments in platelets and red blood cells as
well. Erythropoietin may increase red blood cell production, but most patients with
aplastic anemia already have a very high erythropoietin level. Other cytokines such as
interleukin-3 (IL-3), IL-6 and IL-11 may also have a role in raising platelet and white
cell counts but these agents are currently available only as part of clinical research
trials.
Transfusions
Most patients with aplastic anemia will require transfusions of red blood cells and/or
platelets. Transfusions should come from the fewest donors possible. If bone marrow
transplantation is even a remote possibility, transfusions should not come from family
members. Because most patients will require many transfusions over time, all blood
products starting with the first transfusion should be leukocyte depleted. That is, all red
cells and platelets should be either filtered through a white cell leukocyte depletion filter
or be washed prior to administration to the patient. If possible, all blood products
should be irradiated as well.
Blood and platelet transfusions should be given as infrequently as possible. Many
patients with aplastic anemia do not receive routine platelet transfusions. Rather, they
should be given such products only when there is evidence of clinical bleeding or prior
to invasive procedures. Healthy young patients may tolerate a hemoglobin of between 5
and 7 grams/dl without difficulty. !atients with heart disease or other medical
conditions may need higher hemoglobin levels. !atients who become alloimmunized
(fail to raise their platelet count in response to platelet transfusions) may have less
bleeding symptoms if the hemoglobin is kept between 8 and 10 gm rather than at the
lower values.
atural History and Prognosis
!atients with severe or very severe aplastic anemia are at greatest risk from
overwhelming infection due to the low number of white blood cells. Such patients
should be advised to seek medical attention for any febrile illness. When a fever
develops, it is recommended that a blood culture be obtained and that they receive
parenteral antibiotics active against gram-positive and gram-negative bacteria for at
least 48 hours or until the fever ends and the blood cultures are negative. If the patient
appears clinically ill or the fever is prolonged, anti-fungal and/or anti-viral agents
should also be considered. Even with this approach many patients with low granulocyte
counts succumb to overwhelming infections. Other patients may have life-threatening
bleeding episodes.
Classically it was reported that one-third to one-half of all patients diagnosed with
severe or very severe aplastic anemia would be dead in six months regardless of
therapy. However, HLA-identical sibling donor bone marrow transplantation in large
centers has a long-term survival rate exceeding 80%. Newer combined modality
immunosuppressive therapy shows a response rate over 60%.
In summary, the prognosis for the patient with aplastic anemia today is improving.
!atients faced with such a diagnosis may be helped by the peer support and
educational materials available from the Aplastic Anemia Foundation of America
(AAFA). Members of the AAFA Medical Board are also willing to advise physicians about
their patient's specific situation.