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ANEMIA OF ACUTE AND CHRONIC BLOOD LOSSBLOCK
18
MG Alfeche, MD MODULE2
LECTURE2
December 2, 21!, 8"m#1"m
OUTLINE
I. Overview of Acute and Chronic Blood LossII. Acute Blood Loss
III. Classication of AnemiaIV. Hemolytic AnemiaA. Non-immune Hemolytic Anemia. !icroan"io#athic Hemolytic Anemia
a. $hrom%otic $hrom%ocyto#enic
&ur#ura'. !acroan"io#athic Hemolytic Anemia
a. !arch Hemo"lo%inuria%. $raumatic Cardiac Hemolytic
Anemia(. Hemolytic anemia resultin" from a
chemical or #hysical a"ent). Hemolytic anemia resutin" from
infectious a"entB. Immune Hemolytic Anemia. Autoimmune Hemolytic Anemia
a. *arm +eactin" Anti%odies%. Cryo#athic Hemolytic Anemia
c. Alloimmune Hemolytic ,isease of
the New%orn'. ,ru"-induced Hemolytic Anemia
V. Chronic Blood Loss. Chronic I %leedin"
'. A%normal Va"inal Bleedin"VI. Hy#o#roliferative Anemia
. Iron ,eciency Anemia'. Anemia of +enal ,isease
(. Anemia of Hy#ometa%olic state
/i##ed to#ics
I. &aro0ysmal Noctural Hemo"lo%inuraII. La%oratory $ests
O$ER$IE%
BLEEDING & used to descri%e %lood loss
# Blood loss inside the %ody 1I'(er'"l)# Blood loss outside the %ody 1E*(er'"l)
INTERNAL BLEEDING 2 %lood lea/s out throu"h dama"e to a %lood vessel or or"an
E+TERNAL BLEEDING & occurs either when %lood e0its3
$hrou"h a %rea/ in the s/in
$hrou"h natural o#enin"s3
!outh
Nose 1Nose %leedin"4
Va"ina 1menstruation4
+ectum 1haemorrhoids5 anal se04
ACUTE BLOOD LOSS & A condition in which a #atient 6uic/ly loses a lar"e volume of circulatin"
hemo"lo%in
CHRONIC BLOOD LOSS &A condition wherein the %lood loss develo#s slowly over time and sym#toms
may %e %arely noticea%le and "radually worsen
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Normal3 #in/ish s/in7 fast ca#illary rell Anemic3 #ale s/in7 slow ca#illary rell
CASE-
A '8 year-old colle"e student was %rou"ht to the
emer"ency room due to a vehicular accident.
&ertinent &.9.3
&ale5 unconscious5 stretcher-%orne
B&: ;8
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&ulmonary
Intracranial Tr"m"
Hemrrh"5e
Me'3(r"l 67
Heml303 & increases erythrocyte destruction
Tr"m"(0c blee40'5
Caused %y inDury# unshot wounds# Crushin" inDuries# &uncture wounds - /nife
Me40c"l C'40(0'3
Hemo#hilia
Intracranial Intra-a%dominal
!enorrha"ia
EBLOOD LOSS CAUSES ANEMIA B. THE FOLLO%ING MECHANISMS-
By the direct loss of red %lood cells
If the %lood loss is #rotracted
,ecreased iron stores
Iron ,eciency Anemia
ACUTE BLOOD LOSS
Blood loss causes anemia in ' mechanisms319 :3(#Hemrrh"50c A'em0"
90ternal- $rauma- O%stetric hemorrha"e
Internal
- astrointestinal %leedin"- +u#tured s#leen- +u#tured ecto#ic #re"nancy- u%arachnoid hemorrha"e
29 Heml303
EOTHER MANIFESTATIONS OF ACUTE BLOOD LOSS-. Chest discomfort
'. Arm or %ac/ discomfort Hemarthrosis(. Nec/ or Daw discomfort
!ulti#le myeloma which may re#resent as stiF nec/). $rou%le %reathin"5 with or without chest discomfort. ?eelin" li"ht-headed or %rea/in" into a cold sweat=. ?eelin" sic/ or discomfort in your stomach
If youn" woman you may consider "ynecolo"ic #ro%lems li/e ecto#ic #re"nancy5ovarian ru#tured cyst
MILD BLOOD LOSS 2 9nhanced o0y"en delivery is achieved3
- $hrou"h chan"es in the O'-H% dissociation curve mediated %y a decreased #H orincreased CO' ;Bhr E
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Hematocrit and hemo"lo%in levels do not re@ect the volume of %lood lost
1#1!> l33 f (("l bl4 /lme si"ns of vascular insta%ility
o hy#otension
o decreased or"an #erfusion
?=> "c(e bl4 l33 & failure to com#ensate with the usual mechanism of vascular
contraction and chan"es in re"ional %lood @owo #atient remains in su#ine #osition
o #ostural hy#otension
o tachycardia
?@> "c(e bl4 l33 more than ' liters 1avera"e siGed adult4
o H/lem0c Shc
- Confusion- ,ys#nea- ,ia#horesis- Hy#otension- $achycardia
o Imme40"(e /lme rel"ceme'(
ACUTE HEMOL.SIS 2 increased red cell destruction
Sm(m3 f m4er"(e "'em0"-# ?ati"ue# Loss of stamina# Breathlessness# $achycardia
%h"( "re (he 305'3 f Ac(e G"3(r0'(e3(0'"l Blee40'5- Hy#otension 1systolic B& 8mmH"4- $achycardia 1J'8 %#m4- Orthostatic chan"es in B&
- Blood or coFee-"round-li/e material in N$ as#irate
I in ori"in Hematemesis3 vomitin" of %lood HematocheGia3 fresh %lood from stool
THREE CLINICAL:ATHO:H.SIOLOGIC STAGES
OF ACUTE BLOOD LOSS
19 H.:O$OLEMIA
Loss of consciousness
Acute renal failure
# Blood count will not show anemia since H% level is not aFected# +elease of vaso#ressin and other #e#tide caused %y %arorece#tors and stretch rece#tors
Hy#ovolemiawhich #oses a threat #articularly to or"ans
that normally have a hi"h %lood su##ly5 li/e the %rain
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and the /idneys7 therefore5 loss of consciousness and
acute renal failure are maDor threats
HarrisonKs Boo/ of Internal !edicine thedition
29 HEMODILUTION# shift of @uid from the e0travascular to the intravascular com#artment
As an emer"ency res#onse5 %arorece#tors and stretch
rece#tors will cause release of vaso#ressin and other
#e#tides5 and the %ody will shift @uid from the
e0travascular to the intravascular com#artment5
#roducin" H9!O,IL$ION thus hy#ovolemia "radually
converts to anemia
$he de"ree of anemia will re@ect the amount of %lood
lost. If after ( days the hemo"lo%in is5 for e0am#le5 >
"
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and correctin" the cause of the anemia is the
rst #riority and %lood transfusion may not %e
even necessary %ecause the %ody is ada#ted to
the anemia5 with acute %lood loss the reverse is
true %ecause the %ody is not ada#ted to the
anemia5 %lood transfusion ta/es #riority
29 *hile the emer"ency is %ein" confronted5 it is
im#erative to sto# the hemorrha"e and toeliminate its source
Blood loss durin" and immediately after sur"ery5 which
can %e su%stantial 1e.".5 u# to ' L in the case of a radical
#rostatectomy4. Of course with elective sur"ical
#rocedures5 the #atientKs own stored %lood may %e
availa%le 1throu"h #reo#erative autolo"ous %lood
donation45 and in any case5 %lood loss ou"ht to have
%een carefully monitored
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i. ?anconi anemiaii. chwachman syndromeiii. ,ys/eratosis con"enital
%. 9rythroid #ro"enitor cell failurec. ?unctional im#airment of erythroid and other #ro"enitors due to nutritional and
other causes
B. Increased +ed Cell ,estruction. Ac6uireda. !echanical
i. !acroan"io#athic 1!arch hemo"lo%inuria5 articial heart valves4ii. !icroan"io#athic 1,IC5 $$&5 Vasculitis4iii. &arasites and microor"anisms 1malaria5 %artonellosis5 C. welchii4iv. Chemical inDury and com#le0 chemicalsv. &hysical inDury
%. ,ru"-mediated Hemolysisc. Anti%ody-mediated
i. *arm-ty#e autoimmune hemolytic anemiaii. Cryo#athic syndromes 1cold a""lutinin disease5 #aro0ysmal cold
hemo"lo%inuria5 cryo"lo%ulinemia4iii. $ransfusion reactions 1immediate and delayed4
c. Hy#ers#lenismd. +ed cell mem%rane disorders
i. #ur cell hemolysisii. Ac6uired acanthocytosis and ac6uired stomatocytosis
'. Hereditary
a4 Hemo"lo%ino#athies%4 +ed cell mem%rane disordersc4 +ed cell enGyme defectsd4 &or#hyrias
C. Blood loss and %lood redistri%ution
Only way to re#lace %lood loss is %lood transfusion unit of #ac/ed +BC will re#lace "
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+ed %lood cell destruction can occur in the e0travascular
or intravascular s#ace
90travascular Hemolysis
- red %lood cells are #ha"ocytiGed %y
reticuloendothelial cells5 the mem%rane
structure is %ro/en down5 and the hemo"lo%in is
reduced to its essential com#onents- Iron is recovered for trans#ort %y transferrin
%ac/ to the erythroid marrow. $he #or#hyrin rin"
is %ro/en5 and a molecule of car%on mono0ide is
released.- $he remainin" #ortion of the #or#hyrin rin" is
then trans#orted as %iliru%in to the liver for
conDu"ation and e0cretion in %ile.
Intravascular hemolysis
- red cell destruction5 free hemo"lo%in %inds
either to ha#to"lo%in or hemo#e0in or is
converted to methemal%umin.
- $hese #roteins are cleared %y the liver where theheme is %ro/en down to recover iron and
#roduce %iliru%in
Hematolo"y in Clinical &ractice thedition
-&ossi%le causes3
I'fec(0'3 1note3 ,irect Coom%s test is sometimes #ositive in hemolytic anemia due to
infection4
!alaria
Ba%esiosis e#ticemia
Membr"'e 403r4er3
&aro0ysmal nocturnal hemo"lo%inuria 1+are ac6uired clonal disorder of red %lood
cell surface #roteins4
Liver disease
Dr5#0'4ce4 Heml303
I'(r"cr3cl
"r Defec(3
E*(r"cr3cl
"r Defec(3Here40("r Hemo"lo%ino#at
hies
9nGymo#athies
!em%rane-
cytos/eletal
?amilial
hemolytic uremic
syndrome 1H4
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defectsAc0re4 &aro0ysmal
Nocturnal
Hemo"lo%inuria
1&NH4
!echanical
destruction
1microan"io#athi
c4
$o0ic a"ents
,ru"s
Infectious
Autoimmune
Ge'er"l E*"m0'"(0' "'40ce, "llr
Other #hysical ndin"s #leen may %e enlar"ed7
%ossin" of the s/ull in
severe con"enital casesHemo"lo%in ?rom normal to severely
reduced!CV5 !CH sually increased+eticulocytes IncreasedBiliru%in Increased 1mostly
unconDu"ated4L,H Increased 1u# to 80
normal with intravascularhemolysis4
Ha#to"lo%in +educed to a%sent
NON#IMMUNE HEMOL.TIC ANEMIA
Re4 cell fr"5me'( 3'4rmeMech"'0c"l De3(rc(0' f re4 cell3
!icroan"io#athic hemolytic anemia
!acroan"io#athic hemolytic anemia
Chemical a"ents
Infectious a"ents
Her3le'03m
:"r*3m"l Nc(r'"l Hem5lb0'r0"
MICROANGIO:ATHIC HEMOL.TIC ANEMIA# Intravascular hemolysis caused %y fra"mentation of normal red cells #assin" throu"h
a%normal arterioles# De30(0' f l"(ele(3 "'4 br0'2 the most common cause of microvascular lesions# Chronic and iatro"enic
!icroan"io#athic hemolytic anemias 1!AHAs4
# are a "rou# of #otentially life-threatenin"
disorders characteriGed %y +BC ?ra"mentationand throm%ocyto#enia
# $he +BC fra"mentation occurs intravascularly %y
the mechanical shearin" of +BC mem%ranes as
the cells ra#idly #ass throu"h tur%ulent areas of
small %lood vessels that are #artially %loc/ed %y
microthrom%i dama"ed endothelium# #on shearin"5 +BC mem%ranes 6uic/ly reseal
with minimal esca#e of hemo"lo%in5 %ut the
resultin" fra"ments 1called schistocytes4 are
distorted and %ecome ri"id.# $he s#leen clears the ri"id +BC fra"ments from
the circulation throu"h the e0travascular
hemolytic #rocess
ETIOLOG. AND :ATHOGENESIS-
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Intravascular coa"ulation5 with de#osition of #latelets and %rin in small arterioles 2 the
common antecedent +ed cells stic/ to %rin and are fra"mented %y force of %lood @ow resultin" in %oth
intravascular and e0travascular hemolysis
UNDERL.ING DISORDERS- Invasive carcinoma
Com#lications of #re"nancy3 #re-eclam#sia5 eclam#sia5 a%ru#tio #lacentae !ali"nant hy#ertension
$$&5 H
,ru"s3 antineo#lastic a"ents5 most often m0(mc0', %ut also include %leomycin5
daunoru%icin in com%ination with cytosine ara%inoside5 cis#latin 1H may occur wee/s ormonths after discontinuin" mitomycin thera#y4
&osttrans#lation of /idney or liver
&ost-allo"eneic or autolo"ous marrow trans#lantation
eneraliGed vascultis associated with immune disorders. 903 L95 #olyarteritis nodosa5
*e"enerKs "ranulomatosis5 scleroderma 1Connective tissue disorders4 LocaliGed vascular a%normalities3 cutaneous cavernous heman"iomas5
heman"ioendothelioma of the liver
THROMBOTIC THROMBOC.TO:ENIC :UR:URA# CharacteriGed %y the #resence of throm%ocyto#enia5 microan"io#athic hemolytic
anemia5 neurolo"ic sym#toms 1headache5 confusion5 seiGure5 #aresis5 dys#ha"ia45 renalinvolvement and fever
# Consistent with severe hemolysis5 mar/edly increased s. L,H5 increased indirect%iliru%in
# !icrosco#ic hematuria and #roteinuria also #resent
rine of #atients with $$&3 tea colored due to increased indirect %iliru%in $ea colored urine can also %e due to #rimary liver disease If there is increased in conDu"ated %iliru%in most li/ely it is caused %y liver disease
$here is diFerent shades of Daudince
o Hemoytic3 #ale yellowo He#atic3 dar/ or dee# yellow
CLINICAL FEATURES- ym#toms and si"ns are related to the #rimary #rocess and to the or"ans aFected %y
the intravascular de#osition of #latelets and %rin Blood lm3 schistocytes5 helmet cells5 trian"ular cells5 s#herocytes7 elevated reticulocyte
count Increased concentrations of #lasma hemo"lo%in5 urine hemo"lo%in5 and hemosiderin
s. L,H increased
Coa"ulation a%normalities due to consum#tion coa"ulo#athy
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TREATMENT-o !ana"ement of the #rimary #rocess
o u##ortive3 re4 cell (r"'3f30'3 1to maintain ade6uate level of H%4 and l"(ele(
(r"'3f30'31for %leedin" due to throm%ocyto#enia4
MACROANGIO:ATHIC HEMOL.TIC ANEMIA
MARCH HEMOGLOBINURIA
- Acute and self-in@icted- !ild anemia occurs in individuals involved in sustained5 strenous #hysical activity
:ATHOGENESIS- Hemo"lo%inuria may occur from trauma sustained %y intravascular red cells in the feet
of lon" distance runners or in the hands of /arate #ractitioners or in #ersons #layin" thecon"a drums
astrointestinal %leedin" occurs in '8 of lon" distance runners 1usually not enou"h to
cause anemia4
CLINICAL FEATURES- Concentration of H% and Hct are at lower limits of normal
+BCs tend to %e macrocytic
Increased reticulocyte count Hemo"lo%inuria may %e noted for = to ' hours in runners after a race
THERA:.-o +eassure the #atient
o Add cushioned insoles to the shoes
o #orts anemia3 no treatment
A'em0" "l3 ccr3 0' ASTRONAUTS
- Caused %y a decrease in #lasma volume5 followed %y a decrease in erythro#oietinlevels5 and the rate of red cell #roduction. *hen the #lasma volume is restored afterreentry an anemia is evident
TRAUMATIC CARDIAC HEMOL.TIC ANEMIA
- Com#lications of #rosthetic heart valves that lead to tur%ulence and hi"h shear stresseswithin a s#ace enclosed %y a forei"n surface resultin" in red cell fra"mentation andhemolysis
- Cardiac valve disorders5 es#ecially severe aortic or su%aortic stenosis5 may also causehemolysis
CLINICAL FEATURES- Hemolytic anemia is usually mild and com#ensated %ut may %e severe
&resence of throm%o"enicity of non-endothelialiGed surfaces5 which #romote #latelet
throm%osis and em%oliGation
Blood lm3 schistocytes5 helmet cells5 trian"ular cells5 and s#herocytes #resent. mallhy#ochromic cells may %e #resent
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Increased reticulocyte count5 increased s. L,H5 increased #lasma H%5 urine hemosiderin
#resent ti"mata of iron deciency3 includin" a hi"h unsaturated iron-%indin" ca#acity and a low
serum ferritin ,ecreased #latelet count may indicate #latelet throm%i on valve surfaces
THERA:.-
o +e#lace urinary iron loss with ?eO)o ?or severe anemia re#lacement of #rosthesis
o Blood transfusion
o +ecom%inant 9&O treatment for severe anemia ineli"i%le for reo#eration
HEMOL.TIC ANEMIA RESULTING FROM A
CHEMICAL OR :H.SICAL AGENT- Certain dru"s can induce hemolysis in individuals with a%normalities of erythrocytic
enGymes5 li/e =&, deciency or with an unsta%le H%- Common chemicals3
ARSENIC H.DRIDE
Inhalation of arsenic "as can lead to severe anemia5 hemo"lo%inuria5 and Daundice
LEAD
Lead #oisonin" in CHILDREN- due to in"estion of lead #aint @a/es or chewin" lead-
#ainted o%Dects
Lead #oisonin" in ADULTS- due to industrial e0#osure
Into0ication leads to anemia inhi%ition of heme synthesis modest decrease inred cell life s#an
Inhi%its #yrimidine K-nucleotidaseres#onsi%le for the %aso#hilic sti##lin"
+in"ed sidero%lasts are fre6uently found in the marrow
CO::ER !ay %e induced %y hi"h levels of co##er in #atients hemodialyGed with @uid
contaminated %y co##er tu%in"
Caused %y inhi%ition of several erythrocyte enGymes
%ATER
Administered intravenously5 inhaled in near-drownin"5 or "ainin" access to the
circulation durin" irri"ation #rocedures can cause hemolysis
O+.GEN
HA has develo#ed in #atients receivin" hy#er%aric o0y"enation and in astronauts
e0#osed to 88 o0y"en
INSECT AND ARACHNOID $ENOMS
evere hemolysis may occur in #atients followin" %ites %y %ees5 was#s5 s#iders5
scor#ions
na/e %ites only +A+9L cause hemolysis
HEAT
90tensive %urns may develo# severe HA result of direct dama"e to the red cells
%y heat
DRUGS AND CHEMICALS THAT HA$E BEEN RE:ORTED TO CAUSE CLINICALL.SIGNIFICANT HEMOL.TIC ANEMIA
CHEMICALS DRUGSAniline Amyl nitrate
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A#iol
,ichloro#ro# 1her%icide4
?ormaldehyde
Hydro0yllamines
Lysol
!ineral s#irits
Nitro%enGene
+esorcin
!e#henesin
!ethylene %lue
Ome#raGole
&entachloro#henol
&henaGo#yridine
alicylaGosulfa#yridine
HEMOL.TIC ANEMIA RESULTING FROM
INFECTIOUS AGENTSMECHANISMSHemolysis may %e caused %y3 ,irect invasion %y infectin" or"anism 1!alaria4
9la%oration of hemolytic to0ins 1C. perfringens)
,evelo#ment of autoanti%odies a"ainst red %lood cells anti"ens 1Mycoplasma pneumoniae)
ETIOLOGIC AGENTS-
Aspergillus
Babesia microti and Babesia divergens
Bartonella bacilliformis
Campylobacter jejuni
Clostridium welchii
Coxsackie virus
Cytomegalovirus
iplococcus pneumoniae
!pstein"Barr virus
!scherichia coli
#aemophilus in$uen%a
#epatitis A
#epatitis B
#erpes simplex virus
#&'
&n$uen%a A
(eishmania donovani
(eptospira ballum andor butembo
M"l"r0" & worldKs most common cause of hemolytic anemia
Mumps virus
M. tuberculosis
M. pneumoniae
*eisseria intracellularis
+arvovirus B,-
+lasmodium falciparum
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IMMUNE HEMOL.TIC ANEMIA
Imm'e Heml(0c A'em0"3
$hese can arise throu"h at least two distinct
mechanisms
19 $here is a true autoanti%ody directed a"ainsta red cell anti"en5 i.e.5 a molecule #resent on the
surface of red cells.29 *hen an anti%ody directed a"ainst a certain
molecule 1e.".5 adru"4 reacts with that molecule5
red cells may "et cau"ht in the reaction5
where%y they are dama"ed or destroyed
HarrisonKs Boo/ of Internal !edicine thedition
AUTOIMMUNE HEMOL.TIC ANEMIA
CLASSIFICATION-I. On %asis of serolo"ic characteristics of involved autoimmune #rocess3
A. *arm-autoA% ty#e3 AutoA% ma0imally active at b4 (emer"(re5 (>PCB. Cold-autoanti%ody ty#e3 AutoA% active at tem#erature bel7 (>PCC. !i0ed cold and warm auto-A%s
II. On %asis of #resence or a%sence of underlyin" or si"nicantly associated disorderA9 :r0m"r r 040"(h0c AHAB9 Sec'4"r AHA
. Associated with lym#ho#roliferative disorders 1NHL5Hod"/inKs lym#homa4
'. Associated with the rheumatic disorders(. AssocKd with certain infections
). AssocKd with certain nonlym#hoid neo#lasms 1e0. Ovariantumors4. AssocKd with certain chronic in@ammatory diseases
1e0. lcerative Colitis4=. AssocKd with in"estion of certain dru"s 1methyldo#a4
HEMOL.TIC ANEMIA RESULTING FROM %ARM#REACTING ANTIBODIES
- Caused %y an autoanti%ody directed a"ainst a red cell anti"en- In autoimmune hemolytic anemia 1AHA45 shortened red %lood cell survival result of host
anti%odies that react with autolo"ous +BC- !ost of the #ha"ocytosis 2 mediated red cell destruction ta/es #lace in the s#leen and livere*(r"/"3cl"r heml303
- AHA may %e classied %y the nature of the anti%ody3 M*arm-reactin" A%s have o#timal activity at (>PC
MCold-reactin" A%s show aQnity at lower tem#eratures- %"rm "'(0b4 AHA & most common ty#e- AHA occurs in all a"e "rou#s5 %ut the incidence rises with a"e- !ay %e also classied %y whether an underlyin" disease is #resent 1secondary4 or not
1#rimary or idio#athic4
:r0m"r AHA 2 the autoanti%ody often is s#ecic for a sin"le +BC mem%rane #rotein
su""estin" that an a%%erant immune res#onse has occurred to an autoanti"en or a similarimmuno"en
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Anti%ody-coated +BCs are tra##ed %y macro#ha"es #rimarily in the s#leen5 where they
are in"ested and destroyed or #artially #ha"ocytosed and a s#herocyte with similarsurface area is released.
!acro#ha"es have cell surface rece#tors for the ?c #ortion of I" and fra"ments of C(
and C)%. ,irect +BC lysis %y com#lement is unusual in warm anti%ody AHA5 #ro%a%ly as a result
of interference with com#lement activity %y several mechanisms
Sec'4"r AHA # autoanti%ody most li/ely develo#s from an immunore"ulatory defect
ym#toms are usually slow in onset5 %ut ra#idly develo#in" anemia can occur
&.9. may %e normal if the anemia is mild
#lenome"aly is common %ut not always o%served
Blood lm3 #olychromasia 1indicatin" reticulocytosis4 and s#herocytosis
*ith severe cases5 nucleated +BCs5 +BC fra"ments5 and occasionally5
erythro#ha"ocytosis %y monocytes may %e seen !ild neutro#hilia and normal #latelet count occur
E/"'3 3'4rme & rare condition in which %oth immune-mediated +BC and #latelet
destruction occur
B!A3 erythroid hy#er#lasia nconDu"ated hy#er%iliru%inemia often #resent
,ia"nosis of AHA3 re6uires demonstration of immuno"lo%ulin and
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Cold a""lutinins are I"! autoanti%odies that a""lutinate red cells o#timally %etween 8PC
and PC DONATH#LANDSTEINER ANTIBODIES
sually associated with an acute viral syndrome in children 2 common
Com#lement 0ation occurs at hi"her tem#eratures
- $his is classied as eithero &rimary3 chronic cold a""lutin diseaseo econdary3 "enerally as a result of myco#lasma or infectious mononucleosis
- &ea/ incidence3 #rimary
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ALLOIMMUNE HEMOL.TIC DISEASE OF THE
NE%BORN
,enition3- A disease in which there is fetal to maternal transfer of red cells that results in
immuniGation of the mother- $rans#lacental transfer of maternal anti-red cell anti%odies to the fetus shortens the life
s#an of fetal or new%orn red cells- !anifestations3 anemia5 Daundice5 and he#atos#lenome"aly- In severe cases3 anasarca and /ernicterus
9tiolo"y and &atho#hysiolo"y $rans#lacental #assa"e of fetal cells occurs in >= of #re"nancies
If there is %lood "rou# incom#ati%ility %etween mother and fetus5 the chance of
maternal immuniGation increases with the volume of any trans#lacental haemorrha"e Lar"er volume trans#lacental hemorrha"es are more li/ely to occur at delivery or durin"
invasive o%stetric #rocedures $he ris/ of sensitiGation increases with each trimester of #re"nancy and is "reatest
1=4 at delivery &rior %lood transfusion or a%ortions also can immuniGe the mother
*ithout #ro#hyla0is5 immuniGation occurs in >-; of those at ris/ with an +h-#ositive5
ABO-com#ati%le fetus5 and ' of these with ABO-incom#ati%le fetus Ant-, I" readily crosses the #lacenta and leads to a #ositive anti"lo%ulin test and
hemolysis of the infant In ABO haemolytic disease3 themother is usually ty#e O and the fetus is $y#e A or B
Anti-A and Anti-B ordinarily cause mild and rarely severe hemolysis
Clinical ?eatures *ith severe hemolysis5 #rofound anemia leads to hydro#s fetalis 1anasarca caused %y
cardiac failure45 and most such features die in utero *ith milder cases3 hemolysis #ersists until incom#ati%le +BCs or the oFendin" I" is
cleared 1Half-life of I"3 ( wee/s4 !ost aFected infants are not Daundiced at %irth due to trans#lacental trans#ort of
%iliru%in enerally with mild disease5 the %iliru%in #ea/s at day ) or #ost#artum and declines
slowlt thereafter Increased serum %iliru%in-J /ernicterus 1due to de#osition of unconDu"ated %iliru%in in
the %asal "an"lia and cere%ellum If +h-ne"ative3 should %e tested a"ain at '; wee/s "estation %efore +h immuno"lo%ulin
is "iven
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CASE
R.$.5 a ')-year old em#loyee sou"ht consult at the
9.+. due to diGGiness with tea-colored urine
1S4 fever5 1S4 headache5 1S4 #allor
*hat la%oratory tests are you "oin" to re6uestT
?ollow the @owchart
DRUG#INDUCED IMMUNE HEMOL.TIC ANEMIA# ,ru"s #roduce a #ositive direct anti"lo%ulin test and accelerated red cell destruction
Three mech"'03m3 f 4r5#rel"(e4 0mm'l50c 0'r ( re4 cell3 "re rec5'0e4-19 Ha#ten to 8 daysof treatment
# Ceases a fe7 4"3 ( 2 7ee3 once the dru" is sto##ed
MECHANISMS-19 DRUG ADSOR:TION MECHANISM:e'0c0ll0'3, Ceh"l3r0'3, "'4 S(re(mc0'3
Mechanism
- ?irst5 the dru" is nons#ecically adsor%ed to the #atients red cell- econd5 the dru" must %e a%le to elicit an anti%ody res#onse
$he #atient #roduces an I" anti%ody to a dru". *hen
the dru" is ta/en %y the #atient5 the dru" %inds stron"lyto the #atientKs +BCs. $he I" dru" anti%ody %inds to the
dru" attached to the +BCs5 usually without com#lement
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activation.
Because the oFendin" anti%ody is I" and is stron"ly
attached to the +BCs via the dru"5 hemolysis is
e0travascular %y s#lenic macro#ha"es5 which remove
the anti%ody- and dru"-coated +BCs from the circulation
29 TERNAR. COM:LE+ MECHANISMDr5#A'(0b4 T"r5e(#Cell Cmle*# $he mechanism of red cell inDury is not clearly dened# A##ears to %e mediated %y a coo#erative interaction to "enerate a ternary com#le0
involvin" the 4r5 or 4r5#me("bl0(e5 a 4r5#b0'40'5 membr"'e 30(e on thetar"et cell5 and "'(0b45 with conse6uent activation of com#lement
# $he A% attaches to a 'e"'(05e'consistin" of loosely %ound dru" and red cell A"7%indin" of dru" to the tar"et cell is wea/ until sta%iliGed %y the attachment of the A% to%oth dru" and cell mem%rane
# D0rec( "'(05lbl0' (e3( is usually #ositive with com#lement rea"ents
In ternary dru"-induced hemolysis5 I" anti%odies %ind
dru"-e#ito#e com%ination sites5 called neoanti"ens. $he
dru"-e#ito#e-anti%ody com#le0 on the mem%raneactivates com#lement to tri""er acute intravascular
hemolysis5 often with throm%ocyto#enia.
$he dru"s most often im#licated are 6uinidine5
#henacetin5 and sti%o#hen. Hemolysis occurs after short
#eriods of administration or u#on readministration. $he
,A$ detects only com#lement. In the indirect
anti"lo%ulin test usin" rea"ent +BC5 the serum is
reactive in the #resence of the dru".
Imm'e Cmle* Mech"'03m- PI''ce'( B3("'4erQCl'040'e "'4 :he'"ce(0'
ome dru"s can cause an immune hemolytic anemia
even thou"h they do not %ind to +BCs. $hese dru"s5%ound to #lasma #roteins5 stimulate the formation of
com#lement-0in" anti%odies that activate the classical
com#lement #athway. enerated C(% %inds to the +BC5
which leads to intravascular hemolysis of these
0''ce'( b3("'4er3M.
=9 AUTOANTIBOD. MECHANISM !echanism %y which the dru" can induce formation of an autoanti%ody is un/nown
&ositive direct anti"lo%ulin test3 ;-(= of those ta/in" "lh"#me(hl4"
&ositive test develo#s (-= months after the start of thera#y
Less than of those ta/in" al#ha-methyldo#a develo# hemolytic anemia
A%s in the serum or eluted from +BCs react o#timally at (>PC with autolo"ous or
homolo"ous +BCs in the a%sence of dru" As in Autoimmune HA5 these A%s fre6uently react with the +h com#le0
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,estruction of +BCs occurs chie@y %y s#lenic se6uestration of I"-coated +BCs
A dru" induces the #atient to #roduce I" warm-reactive
autoanti%odies a"ainst +BC selfanti"ens. $hese
autoanti%odies react at (>U C5 and the la%oratory
ndin"s are indistin"uisha%le from those in *AIHA.
Hemolysis is e0travascular and is mediated %y
macro#ha"es
#redominantly in the s#leen.
Me(hl4"#I'4ce4 ;A(0mm'e) Mech"'03mMe(hl4" "'4 rel"(e4 4r53 ;Al4me(, L#4")- (re"(me'( f her(e'30'
An induced inhi%ition of $-su##ressor allowin"
uninhi%ited autoanti%ody #roduction %y B cells. ,es#ite
dru" withdrawal5 anti%odies may remain for months
A3 $he anti%ody attaches only to the dru"5 which is
ti"htly %ound to the red %lood cell 1+BC4 mem%rane
1#enicillin ty#e4
B3 $he anti%ody attaches to a neoanti"en created %y
com#onents of %oth the dru" and the +BC mem%rane
16uinidine
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,iGGiness or li"htheadedness
&allor
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# De/elme'("l 3("5e3 f Ir' Dec0e'c-
IRON DE:LETION 2 tora"e iron decreased or a%sent
IRON DEFICIENC. 2 stora"e iron decreased or a%sent with low serum iron
concentration and transferrin saturation
IRON DEFICIENC. ANEMIA 2 stora"e iron decreased or a%sent5 low serum iron
concentration and transferrin saturation5 and low hemo"lo%in level and reducedhematocrit
STAGES OF IRON DEFICIENC.A9 NEGATI$E IRON BALANCE
- ,emands for 1or losses of4 iron e0ceed the %odyKs a%ility to a%sor% iron from the diet- Causes3
Blood loss 1"reater than 8-'8 ml +BCs days
Oral or IV
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?or sym#tomatic elderly #atients with severe iron deciency anemia and
cardiovascular insta%ility
+eserved for those with sym#toms of anemia5 cardiovascular insta%ility5 and
continued and e0cessive %lood loss from whatever source5 and those who re6uireimmediate intervention
ANEMIA OF RENAL DISEASE
# Chronic renal failure is usually seen with moderate to severe hy#o#roliferative anemia# Normocytic5 normochromic +BCs# ,ecreased reticulocytes# ,ue to inade6uate amounts of erythro#oietin and reduction in red cell survival# Normal serum iron5 $IBC5 and ferritin levels
ANEMIA IN H.:OMETABOLIC STATES# &rotein malnutrition causes mild to moderate hy#o#roliferative anemia# +elease of erythro#oietin from the /idney is sensitive to the need for O'# 9ndocrine deciency states3 related to the eFects of andro"en and estro"en# Tre"(me'(-$ransfusions and 9&O
This topic was skipped by doc:
:ARO+.SMAL NOCTURNAL HEMOGLOBINURIA
DEFINITION- An ac6uired hemato#oietic stem cell disorder characteriGed %y a deciency of
#hos#hatidylinositol-anchored #roteins on the surface of hemato#oietic cells- $his leads to com#lement-mediated intravascular hemolysis- $he only haemolytic anemia caused %y an intrinsic defect of the red cell that is ac6uired
E:IDEMIOLOG.- ame fre6uency in men and women- &revalence is to #er million
- No evidence of inherited susce#ti%ility- !edian survival3 ;-8 years- !ay evolve into a#lastic anemia and &NH may manifest itself in #atients who #reviously
had a#lastic anemia- -' -J Acute !yelo"enous Leu/emia
DIAGNOSIS $he classic a%normality is increased sensitivity to com#lement-mediated lysis of
erythrocytes5 detected %y diFerent tests- Acid hemolysis test- ucrose hemolysis test- C,- ne"ative 1&roduct of &I-A "ene4
$he disorder is a conse6uence of somatic mutations which cause an error in synthesis of
the "lycosyl#hos#hatidylinositol 1&I4 anchor ,eciencies in several &I-anchored mem%rane #roteins5 such as decay acceleratin"
factor5 C, 5 C, ;5 C, =5 C, ) have %een identied &I-A "ene 1#hos#hatidylinositol "lycan class A3 -lin/ed "ene which is re6uired for an
early ste# in &I %iosynthesis
CLINICAL FEATURES Nocturnal hemo"lo%inuria is uncommon
Hemo"lo%inuria occurs irre"ularly in most #atients5 #reci#itated %y a variety of events3
infection5 sur"ery5 or contrast dye inDection &atients have chronic haemolytic anemia5 which may %e severe
!odest s#lenome"aly in some #atients
&ancyto#enia is often #resent
Iron deciency as a conse6uence of iron loss in the urine
Bleedin" may occur secondary to throm%ocyto#enia
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Thrmb303 03 rm0'e'( fe"(re
- Venous throm%osis occur fre6uently- Arterial throm%osis also occur- Budd-Chiari syndrome or #ortal vein throm%osis- &ulmonary hy#ertension may develo# secondary to throm%osis in the #ulmonary
microvascular &re"nancy in &NH #atients may %e associated with "br(0' "'4 /e'3
(hrmbembl03m Re'"l m"'0fe3("(0'3 0'cl4e
- Hy#osthenuria- e0cretion of urine of low s#ecic "ravity- A%normal tu%ular function- Acute and chronic renal failure
Nerl50c m"'0fe3("(0'3
- Headache- Cere%ral venous throm%osis uncommon
Clinical ym#toms of &NH3 A $riad of Clinical ?eatures
. Ac6uired cor#uscular haemolytic anemia- Chronic hemolysis or acute hemolysis crises
- Hemosiderinuria5 Iron deciency'. $hrom%o#hilia
- Aty#ical throm%osis3 Budd-Chiari syndrome5 #ortal vein throm%osis5 mesenterialthrom%osis5 cere%ral throm%osis
(. Bone marrow failure- $hrom%ocyto#enia and
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the test documents anemia5 leu/ocyte counts5 and diFerential counts
&latelet count3 e0clude an underlyin" infection or hematolo"ic mali"nancy. $he #latelet
count is within the reference ran"e in most haemolytic anemias $hrom%ocyto#enia can occur in L95 CLL5 and !icroan"i#athic haemolytic anemia.
$hrom%ocyto#enia associated with a #ositive direct Coom%s test result is /nown as9VAN N,+O!9
Re4 bl4 cell I'40ce3 ,ecreased !CV and !CH3
# !icrocytic hy#ochromic anemia3 chronic intravascular hemolysis 1&NH4 Hi"h !CV3 macrocytic anemia
# sually due to me"alo%lastic anemias %ut can occur in liver disease. A hi"hnum%er of reticulocytes also may cause a hi"h !CH
A hi"h !CH and !CHC3 s#herocytosis
Increased +,* study
# !easure of anisocytosis which is li/ely in haemolytic anemia
LABORATOR. TESTS FOR HEMOL.SIS
Serm H"(5lb0' m54L !ost sensitive test for +BC destruction
A "lyco#rotein synthesiGed mainly in the liver
e6uesters free H% released from hemolyGed +BC-J trans#orted %y macro#ha"es to
the liver-J heme %ro/en down to %iliru%in
L"c("(e 4eh4r5e'"3e Increased 1L, J''4
L, occurs in the cyto#lasm of all cells
Increased in all haemolytic anemias
I'40rec( b0l0rb0' nconDu"ated %iliru%in is a criterion for hemolysis5 %ut is not s#ecic %ecause an
elevated %iliru%in is also may indicate il%ert ,isease *ith hemolysis5 the level of indirect %iliru%in usually is less than ) m"
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D0rec( "'4 0'40rec( "'(05lbl0' ;Cmb3) (e3(3
1a4 $he direct anti"lo%ulin test 1,A$4 is #erformed %y
incu%atin" the #atientKs washed red %lood cells 1+BCs4
with a rea"ent that contains anti%odies to I"5 C(
com#lement or %oth 1nons#ecic rea"ent4. A""lutination
of the +BCs indicates that there is either I" or C(5
res#ectively5 %ound to the +BC mem%rane
1%4 $he indirect anti"lo%ulin test is #erformed %y
incu%atin" a normal donorKs washed +BCs with the
#atientKs serum in the #resence of a rea"ent that
contains anti%odies to I"5 C( or %oth. A""lutination of
the +BCs indicates the #resence of an anti%ody5 or
com#lement5 directed toward an +BC cell surface
anti"en in the #atientKs serum
Sec0c 3(40e3 40"5'3e4 b h03(r, :E, er0her"l 3me"r "'4 (her l"b '40'53
,A$ result is usually #ositive in autoimmune haemolytic anemia5 %ut it may %e occasionally
ne"ative in this disorder
rine free H% test reveals hemo"lo%inuria5 which occurs with intravascular hemolysis when the amount of
free H% e0ceed the availa%le ha#to"lo%in. rine may %e dar/ due to hemo"lo%inuria5 %utmyo"lo%inuria #or#hyria5 and other conditions can also cause dar/ urine
rine hemosiderin may su""est intravascular hemolysis. Hemosiderin is detected in s#un urinary sediment
as an iron stain in slou"hed renal e#ithelial cells
+BC survival chromoim- survival is rarely used %ut it can denitely demonstrate a shortened +BC survival 1hemolysis4.
$his test is ordered when the clinical history and la%oratory studies cannot esta%lish adia"nosis of hemolysis
Cold a""lutin titer A hi"h titer of anti-I anti%ody may %e found in myco#lasmal infections and a hi"h titer
of anti-I anti%ody may %e found in hemolysis associated with infectious mononucleosis.An anti-& cold a""lutin may %e seen in &aro0ysmal Cold Hemo"lo%inuria
LALUMA LAM:REA LUCES MOLINA
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