ANEMIA OF ACUTE AND CHRONIC BLOOD LOSS
ANEMIA OF ACUTE AND CHRONIC BLOOD LOSS
BLOCK BLOCK 1818 MG Alfeche, MDMG Alfeche, MD MODULEMODULE
2 2 LECTURE LECTURE 2 2 December 2, 21!, 8"m#1"m December 2, 21!, 8"m#1"m OUTLINE OUTLINE
II.. OOvveerrvviieew w oof Af Accuutte ae annd Cd Chhrroonniic Bc Bllooood Ld Loossss IIII.. AAccuutte e BBllooood d LLoossss
IIIIII.. CCllaassssiiccaattiioon on of Af Anneemmiiaa IIVV.. HHeemmoollyyttiic c AAnneemmiiaa
A.
A. NonNon-im-immumune ne HeHemolmolytiytic Ac Anenemiamia .
. !i!icrcroaoan"in"io#o#athathic Heic Hemomolytlytic Aneic Anemimiaa a.
a. $h$hrorom%om%otic tic $h$hrorom%om%ocytcyto#o#enienicc &ur#ura
&ur#ura '.
'. !a!acrcroaoan"in"io#ao#athithic Hemoc Hemolytlytic Aneic Anemiamia a.
a. !a!arrch ch HeHemomo"l"lo%o%ininururiaia %.
%. $$rauraumatmatic Cic Carardiadiac Hec Hemomolytlyticic Anemia
Anemia (.
(. HeHemomolytlytic aic anenemia mia reresulsultintin" fr" from aom a chemical or #hysical a"ent chemical or #hysical a"ent ).
). HemolHemolytiytic ac anemnemia ria resuesutintin" fr" fromom infectious a"ent
infectious a"ent B.
B. ImmuImmune Hne Hememololytytic Aic Anenemimiaa .
. AutAutoimoimmumune ne HeHemolmolytiytic c AnAnemiemiaa a.
a. **ararm m +e+eacactintin" " AntAnti%i%odiodieses %.
%. CryCryo#ao#athithic c HeHemolmolytiytic c AnAnemiemiaa c.
c. AllAlloioimmummune ne HemHemololytiytic ,c ,iseisease ase of of the New%orn
the New%orn '.
'. ,ru"-,ru"-indinducuced ed HeHemolmolytiytic Ac Anenemiamia V
V.. CChhrroonniic c BBllooood d LLoossss .
. ChChroroninic c I I %l%leeeedidin"n" '.
'. A%A%nornormal mal VVa"ia"inal nal BleBleededin"in" V
VII.. HHyy##oo##rroolliiffeerraattiivve Ae Anneemmiiaa .
. IrIron on ,e,eccieiencncy Ay Anenemimiaa '.
'. AnAnememia ia of of ++enenal al ,i,iseseasasee (.
(. AneAnemia mia of of Hy#Hy#omometaeta%ol%olic ic stastatete /i##ed to#ics
/i##ed to#ics
II.. &&aarroo00yyssmmaal l NNooccttuurraal l HHeemmoo""lloo%%iinnuurraa IIII.. LLaa%%oorraattoorry y $$eessttss
O$ER$IE% O$ER$IE%
BLEEDING &BLEEDING & used to descri%e %lood lossused to descri%e %lood loss ## Blood loss inside the %ody 1Blood loss inside the %ody 1 I'(er'"l)I'(er'"l) ## Blood loss outside the %ody 1Blood loss outside the %ody 1E*(er'"l)E*(er'"l) INTERNAL BLEEDING
INTERNAL BLEEDING 2 %lood lea/s out throu"h dama"e to a 2 %lood lea/s out throu"h dama"e to a %lood vessel or or"an%lood vessel or or"an E+TERNAL BLEEDING &
E+TERNAL BLEEDING & occurs either when %lood e0its3occurs either when %lood e0its3 $hrou"h a
$hrou"h a %rea/ in %rea/ in the s/inthe s/in $hrou"h na
$hrou"h natural o#enin"stural o#enin"s33 !outh
!outh
Nose 1Nose %leedin"4 Nose 1Nose %leedin"4 Va"ina 1menstruation4 Va"ina 1menstruation4
+ectum 1haemorrhoids5 anal se04 +ectum 1haemorrhoids5 anal se04
ACACUTUTE E BLBLOOOOD D LLOSOSS S && A A conconditdition ion in in whwhich ich a a #a#atietient nt 6ui6uic/lc/ly y loloses ses a a lalar"r"e e volvolume ume of of circirculculatiatin"n" hemo"lo%in
hemo"lo%in
CHRONIC BLOOD LOSS &CHRONIC BLOOD LOSS & A condition wherein the %lood loss develo#s slowly over time and sym#toms A condition wherein the %lood loss develo#s slowly over time and sym#toms may %e %arely noticea%le and "radually worsen
may %e %arely noticea%le and "radually worsen
&a"e
Normal3 #in/ish s/in7 fast ca#illary Normal3 #in/ish s/in7 fast ca#illary rellrell
Anemic3 #ale s/in7 slow ca#illary rellAnemic3 #ale s/in7 slow ca#illary rell
CASE-•
• A '8 year-old colle"e student was %rou"ht to theA '8 year-old colle"e student was %rou"ht to the emer"ency room due to a vehicular accident. emer"ency room due to a vehicular accident.
•
• &ertinent &.9.3&ertinent &.9.3 ⇒
⇒ &ale5 unconscious5 stretcher-%orne&ale5 unconscious5 stretcher-%orne ⇒
⇒ B&: ;8<=8 mmH"7 C+ : '> %#m7 ++ : ' c#mB&: ;8<=8 mmH"7 C+ : '> %#m7 ++ : ' c#m ⇒
⇒ $ $achycardicachycardic ⇒
⇒ hallow %reathin"5 decreased %reath sounds5 lefthallow %reathin"5 decreased %reath sounds5 left lun" eld
lun" eld
Blood &ressure3 Hy#otensionBlood &ressure3 Hy#otension
Cardiac +ate3 $achycardicCardiac +ate3 $achycardic
Clinical Im#ressionClinical Im#ression
o
o Blunt trauma in the Blunt trauma in the lun"s leadin" to Intlun"s leadin" to Internal %leedin" ernal %leedin" and %lood loss and %lood loss ma/in" thema/in" the
#atient hy#otensive #atient hy#otensive
o
o ?irst Aid3?irst Aid3
Chec/ for Airway5 Breathin" and Chec/ for Airway5 Breathin" and CirculationCirculation
tart on IV @uidstart on IV @uids
+e6uest for CBC5 Chest ray5 AB5 +e6uest for CBC5 Chest ray5 AB5 Blood $Blood $y#in" for y#in" for Blood transfusionBlood transfusion
Indications for Blood $ransfusionIndications for Blood $ransfusion
o
o Acute Blood Loss secondary to traumaAcute Blood Loss secondary to trauma
OB-N9 %lood loss 1massive4OB-N9 %lood loss 1massive4
o
o Chronic %lood loss Chronic %lood loss 1ive &ac/ed +BC41ive &ac/ed +BC4
Acute %lood loss Acute %lood loss
-- hahas a dis a direrect ict im#m#acact on tt on the ihe intnte"e"ririty oty of thf the %le %loooodd volu
volume me and and o0yo0y"en su##ly "en su##ly to to tissutissues. es. uddudden5en5 se
seververe e hahaemoemorrrrha"ha"e e can can indinduce uce hyhy#ov#ovoleolemicmic shoc
shoc/5 /5 cardcardiovasiovasculacular r failufailure5 re5 and and deatdeath. h. *he*henn %lood loss is more "radual5 the hemo"lo%in level %lood loss is more "radual5 the hemo"lo%in level can fall to a #oint where o0y"en delivery to vital can fall to a #oint where o0y"en delivery to vital o
orr""aanns s iis s ccoomm##rroommiisseedd Chronic %lood loss
Chronic %lood loss -
- wwilill l ddee##lelette e iriron ston stororees s anand d ##rrododucuce e aan n iirronon de
decicienency cy ananemiemia. a. $he$herereforfore5 e5 diadia"n"nosiosis s andand m
maannaa""eemmeennt t oof f aa %lo
%lood od losloss s aneanemia mia mumust st ta/ta/e e intinto o accaccounount t thethe reason %ehind the loss5 the rate and amount of reason %ehind the loss5 the rate and amount of %lo
%lood od losloss5 s5 and the and the caca#ac#acity of ity of the #atithe #atienent t toto com#ensate for %oth volume losses and anemia com#ensate for %oth volume losses and anemia
Hematolo"y on Clinical &ractice
Hematolo"y on Clinical &ractice thth edition edition
ETIOLOG. OF ACUTE BLOOD LOSS ETIOLOG. OF ACUTE BLOOD LOSS
Ob/03 bl4 l33 Ob/03 bl4 l33
astrointest
&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 • 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 ' mechanisms3 19 :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"nancy5 ovarian 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 or increased CO' ;Bhr E<ec()
- In acute %lood loss5
• Hy#ovolemia dominates
&a"e = of 2 Me40c"l C'40(0'3
• 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 @ow
o #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$OLEMIA
Loss of consciousness Acute renal failure
# Blood count will not show anemia since H% level is not aFected
# +elease of vaso#ressin and other #e#tide caused %y %arorece#tors and stretch rece#tors
Hy#ovolemia which #oses a threat #articularly to or"ans that normally have a hi"h %lood su##ly5 li/e the %rain
and the /idneys7 therefore5 loss of consciousness and acute renal failure are maDor threats
HarrisonKs Boo/ of Internal !edicine th edition
29 HEMODILUTION
# shift of @uid from the e0travascular to the intravascular com#artment
As an emer"ency res#onse5 %arorece#tors and stretch rece#tors will cause release of vaso#ressin and other #e#tides5 and the %ody will shift @uid from the e0travascular to the intravascular com#artment5 #roducin" H9!O,IL$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 > "<dL5 it means that a%out half of the entire %lood has %een lost.
HarrisonKs Boo/ of Internal !edicine th edition
=9 BONE MARRO% RES:ONSE
& #roduction of #recursor cells wlll com#ensate for the loss - if %leedin" does not continue anemia will %e corrected
- increase in reticulocyte count or #resence of #olychromatic cells and sometimes there will %e reactive throm%ocytosis
,ia"nosis of Acute &osthemorrha"ic Anemia is usually strai"htforward5 althou"h sometimes internal %leedin" e#isodes 1traumatic inDury45 even when lar"e5 may not %e immediately o%vious. *henever an a%ru#t fall in hemo"lo%in has ta/en #lace5 whatever history is "iven %y the #atient5 A&HA should %e sus#ected.
u##lementary history may have to %e o%tained %y as/in" the a##ro#riate 6uestions5 and a##ro#riate investi"ations 1e.".5 a sono"ram or an endosco#y4 may have to %e carried out.
TREATMENT
*ith res#ect to treatment5 a two-#ron"ed a##roach is im#erative
19 Blood lost needs to %e re#laced #rom#tly
# nli/e with many chronic anemias5 when ndin"
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 to eliminate 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<measured. $he fact that this %lood loss is iatro"enic dictates that ever more eFort should %e invested in o#timiGin" its mana"ement
Hl Gr"0l f Emer5e'c Me40c0'e
- for a lon" time has %een the idea of a %lood su%stitute that would %e universally availa%le suita%le for all reci#ients5 easy to store and to trans#ort5 safe5 and as eFective as %lood itself ' main #aths have %een #ursued3
. ?luorocar%on synthetic chemicals that %ond o0y"en reversi%ly
'. Articially modied H%s /nowm as hemo"lo%in-%ased o0y"en carriers
Althou"h there are numerous anecdotal re#orts of the use of %oth a##roaches in humans5 and althou"h HBOCs have reached the sta"e of #hase '2( clinical trials5 no M%lood su%stitute has yet %ecome standard treatment
HarrisonKs Boo/ of Internal !edicine th edition
CLASSIFICATION OF ANEMIA
I9 ABSOLUTE ANEMIA ;decreased red cell volume4 A. ,ecreased red cell #roduction
. Ac6uired
a. &leuri#otent stem cell failure i. A#lastic Anemia
ii. Anemia of leu/emia and of myelodys#lastic syndromes iii. Anemia associated with marrow inltration
iv. &ostchemothera#y '. Hereditary
i. ?anconi anemia
ii. chwachman syndrome iii. ,ys/eratosis con"enital %. 9rythroid #ro"enitor cell failure
c. ?unctional im#airment of erythroid and other #ro"enitors due to nutritional and other causes
B. Increased +ed Cell ,estruction . Ac6uired
a. !echanical
i. !acroan"io#athic 1!arch hemo"lo%inuria5 articial heart valves4 ii. !icroan"io#athic 1,IC5 $$&5 Vasculitis4
iii. &arasites and microor"anisms 1malaria5 %artonellosis5 C. welchii4 iv. Chemical inDury and com#le0 chemicals
v. &hysical inDury %. ,ru"-mediated Hemolysis c. Anti%ody-mediated
i. *arm-ty#e autoimmune hemolytic anemia
ii. Cryo#athic syndromes 1cold a""lutinin disease5 #aro0ysmal cold hemo"lo%inuria5 cryo"lo%ulinemia4
iii. $ransfusion reactions 1immediate and delayed4 c. Hy#ers#lenism
d. +ed cell mem%rane disorders i. #ur cell hemolysis
ii. Ac6uired acanthocytosis and ac6uired stomatocytosis '. Hereditary
a4 Hemo"lo%ino#athies
%4 +ed cell mem%rane disorders c4 +ed cell enGyme defects d4 &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 "<dL of %lood so you have to 6uantify the volume of %lood loss
If the #atientKs H"% is >"<dL how many units of %lood should %e "iven to the #atient to maintain a H"% of 8 "<dL
o Answer3 ( units
II9 RELATI$E ANEMIA# 0'cre"3e4 l"3m" /lme
HEMOL.TIC ANEMIA
-is anemia due to heml3035 the a%normal %rea/down of +BCs either in the %lood vessels 10'(r"/"3cl"r heml303) or elsewhere in the %ody ;e*(r"/"3cl"r heml303)9
-It has numerous #ossi%le causes5 ran"in" from relatively harmless to life-threatenin". $he "eneral classication of hemolytic anemia is either "c0re4 or 0'her0(e4
+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 the heme is %ro/en down to recover iron and #roduce %iliru%in
Hematolo"y in Clinical &ractice th edition
-&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(3 Here40("r Hemo"lo%ino#at hies 9nGymo#athies !em%rane-cytos/eletal ?amilial hemolytic uremic syndrome 1H4
defects Ac0re4 &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 cases Hemo"lo%in ?rom normal to severely
reduced
!CV5 !CH sually increased +eticulocytes Increased
Biliru%in Increased 1mostly unconDu"ated4
L,H Increased 1u# to 80 normal with intravascular hemolysis4
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"mentation and 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
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 or months 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 renal involvement 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 yellow
o 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
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"'3f30'3 1for %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" the con"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#oietin levels5 and the rate of red cell #roduction. *hen the #lasma volume is restored after reentry an anemia is evident
TRAUMATIC CARDIAC HEMOL.TIC ANEMIA
- Com#lications of #rosthetic heart valves that lead to tur%ulence and hi"h shear stresses within a s#ace enclosed %y a forei"n surface resultin" in red cell fra"mentation and hemolysis
- Cardiac valve disorders5 es#ecially severe aortic or su%aortic stenosis5 may also cause hemolysis
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. mall hy#ochromic cells may %e #resent
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 in red cell life s#an
⇒ Inhi%its #yrimidine K-nucleotidase res#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 DRUGS Aniline Amyl nitrate
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 AGENTS
MECHANISMS
Hemolysis 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 &a"e 1= of 2
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"ainst a 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 th edition
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 (>PC B. Cold-autoanti%ody ty#e3 AutoA% active at tem#erature bel7 (>PC C. !i0ed cold and warm auto-A%s
II. On %asis of #resence or a%sence of underlyin" or si"nicantly associated disorder A9 :r0m"r r 040"(h0c AHA
B9 Sec'4"r AHA
. Associated with lym#ho#roliferative disorders 1NHL5 Hod"/inKs lym#homa4
'. Associated with the rheumatic disorders (. AssocKd with certain infections
). AssocKd with certain nonlym#hoid neo#lasms 1e0. Ovarian tumors4
. 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 liver e*(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 similar immuno"en
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 similar surface 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<or com#lement %ound to the +BC
sually achieved %y the direct anti"lo%ulin test 1,A$4 THERA:. FOR HA # %ARM#REACTING
ABS-o enerally5 anemia develo#s slowly so that +BC transfusion is not re6uired o Glccr(0c043 2 6uic/ly slow or sto# hemolysis in '<( of #atients
o ' will achieve a com#lete remission
o Sle'ec(m & removes the main site of +BC destruction
CR.O:ATHIC HEMOL.TIC ANEMIA
- Caused %y autoanti%odies that %ind red cells %est at tem#eratures %elow (>PC5 usually %elow (PC
- !ediated throu"h two maDor ty#es of Mcold anti%ody3 cl4 "55l(0'0'3 and D'"(h# L"'43(e0'er "'(0b40e3
- $he com#lement system #lays a maDor role in red cell destruction
COLD AGGLUTININ#MEDIATED AUTOIMMUNE HEMOL.TIC ANEMIA
⇒ 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 either
o &rimary3 chronic cold a""lutin disease
o econdary3 "enerally as a result of myco#lasma or infectious mononucleosis
- &ea/ incidence3 #rimary<chronic syndrome is in #ersons older than 8 years old
- $his disorder characteristically has monoclonal I"! cold a""lutins and may %e considered a monoclonal "ammo#athy
- Cold a""lutinins %ind red cells in the su#ercial vessels im#edin" ca#illary %lood @ow acrocyanosis
- ,irect lysis results from #ro#a"ation of the full com#lement se6uence
- Commonly5 fra"ments C(% and C)% are de#osited on the red cell surface5 #rovidin" a stimulus for #ha"ocytosis
Re"c(0' "( (emer"(re3 3"ll bel7 =C & (he ccr 0' er0her"l c0rcl"(0' "'4 0' cl4 7e"(her
# Occur in 8-'8 of cases of AHA
# #lenome"aly may occasionally %e seen in the idio#athic form # Anemia is usually mild to moderate
# &B3 autoa""lutination5 #olychromasia5 s#herocytosis # $hera#y3 /ee#in" the #atient warm
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 $y#e A or B
Anti-A and Anti-B ordinarily cause mild and rarely severe hemolysis Clinical ?eatures
*ith severe hemolysis5 #rofound anemia leads to hydro#s fetalis 1anasarca caused %y cardiac failure45 and most such features die in utero
*ith milder cases3 hemolysis #ersists until incom#ati%le +BCs or the oFendin" I" is cleared 1Half-life of I"3 ( wee/s4
!ost aFected infants are not Daundiced at %irth due to trans#lacental trans#ort of %iliru%in
enerally with mild disease5 the %iliru%in #ea/s at day ) or #ost#artum and declines slowlt thereafter
Increased serum %iliru%in-J /ernicterus 1due to de#osition of unconDu"ated %iliru%in in the %asal "an"lia and cere%ellum
If +h-ne"ative3 should %e tested a"ain at '; wee/s "estation %efore +h immuno"lo%ulin is "iven
CASE
• R.$.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<dru" adsor#tion involvin" dru"-de#endent anti%odies 29 $ernary com#le0 formation involvin" dru"-de#endent anti%odies
=9 Induction of autoanti%odies that react with red cells in the a%sence of the incitin" dru" # In #atients receivin" h05h#43e e'0c0ll0' red cells have a su%stantial coatin" of the
dru"
# In a small #ro#ortion of #atients5 an anti#enicillin A% 1usually I"4 develo#s and %inds to the #enicillin on the red cell
# $he 40rec( "'(05lbl0' (e3( #ositive heml(0c "'em0"- occurs after > to 8 days of 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"ly to the #atientKs +BCs. $he I" dru" anti%ody %inds to the
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+ MECHANISM
Dr5#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 the tar"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%rane activates 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("'4erQ Cl'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
,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"'03m
Me(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<sti%o#hen ty#e4
C3 $he anti%ody attaches mainly to the mem%rane5 not re6uirin" the #resence of the dru" 1-methyldo#a ty#e4
CHRONIC BLOOD LOSS
CHRONIC GASTROINTESTINAL BLEEDING
- Bleedin" is slow5 may continue for a lon" time5 or sto# in a short #eriod of time • Hemorrhoids 1Internal5 90ternal4
• In@ammation 19so#ha"itis5 Varices4 • lcers 1astric5 ,uodenal4
• !ali"nancy 1Colonic5 +ectal4 • astritis
# S05'3 "'4 3m(m3 "re le33 b/03 • ?ati"ue<easy fati"a%ility<loss of ener"y • *ea/ness
• ,iGGiness or li"htheadedness • &allor<#ale s/in
• hortness of %reathin"5 es#. on e0ertion • ,iQculty concentratin"
• &al#itations • Chest #ain
• Cold hands and feet • Headache
#
I'/e3(05"(e-• CBC 1+BC indices5 mor#holo"y4 • +eticulocyte count
• ?ecalysis with fecal occult %lood • Iron studies
-
Tre"(me'(-• Control the %leedin" • !edications
• ur"ical intervention
ABNORMAL $AGINAL BLEEDING - Adenomyosis
- Cervical cancer - Cervical #oly#s
- 9ndometrial cancers5 hy#er#lasia - &I,
Chronic %lood loss leadin" to iron deciency is usually caused
%y 5"3(r0'(e3(0'"l bl4 l33. However5 some #atients may #resent with a defect in iron a%sor#tion5 secondary to small-%owel disease5 such as non-tro#ical
s#rue or e0tensive Crohn disease.
&atients who have had a Billroth II o#eration with va"otomy for
ulcer disease can also e0hi%it food iron mala%sor#tion. In develo#in" countries5 hoo/worm infestation is a fre6uent
cause of
chronic %lood loss leadin" to severe iron deciency. Less fre6uently5 #atients can #resent with a %lood loss
anemia secondary
to hemo"lo%inuria 1#aro0ysmal nocrurnal hemo"lo%inuria5 see
Cha#ter 45 #ulmonary hemosiderosis5 or self-induced %lood loss.
H.:O:ROLIFERATI$E ANEMIA # M3( cmm' "'em0"3
# Anemias associated with normocytic5 normochromic +BCs and an ina##ro#riately low reticulocyte res#onse 1reticulocyte inde03 '.8 to '.4
# Includes3
E"rl Ir' Dec0e'c 1%efore hy#ochromic microcytic red cells develo#4 Ac(e "'4 Chr'0c I'6"mm"(0' 1includin" mali"nancies4
Ab'rm"l er(hr0e(0' re3'3e ( "'em0" 1Anemia due to renal disease5 In@ammation5 Cancer5 Hy#ometa%olic states4
Chronic %lood loss can lead to Iron ,eciency Anemia IRON DEFICIENC. ANEMIA
# !ost common chronic maladies in humans
# 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 reduced hematocrit
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<day4
• &re"nancy 1demands for +BC #roduction %y the fetus outstri# the motherKs a%ility to #rovide iron4
• +a#id "rowth s#urts in the adolescent • ,ecreased dietary iron inta/e
- Iron decit is remedied %y mo%iliGation of iron from +9 stora"e sites
Me'rrh"50" & most common cause of iron deency in women
G"3(r0'(e3(0'"l blee40'5 & most common cause of iron deciency in men and #ostmeno#ausal
J m5 & the avera"e iron loss from transfer to fetus and %lood in #lacenta
Lac/ of iron interferes with heme synthesis CLINICAL
FEATURES- eneral sym#toms of anemia
i"ns de#end u#on the severity and chronicity of anemia
Irrita%ility and headache occur fre6uently
&aresthesias and %urnin" of the ton"ue may occur
/oilonychia
Cheilitis
TREATMENT-o IRON RE:LACEMENT
+es#onse to treatment 2 varies de#endin" u#on the erythro#oietin stimulus and the rate of a%sor#tion
+ise in reticulocyte count3 within ) to > days Oral or IV<I!
?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 re6uire immediate 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
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 mesenterial throm%osis5 cere%ral throm%osis
(. Bone marrow failure
- $hrom%ocyto#enia and<or leu/o#enia - A#lastic anemia
LABORATOR. FEATURES
Anemia is the most consistent ndin"
- !ild to severe7 usually normo-macrocytic - Neutro#enia and<or throm%ocyto#enia
- nconDu"ated %iliru%in mildly or moderately elevated - L,H mar/edly elevated
- Ha#to"lo%in usually undetecta%le
!arrow e0am - 9rythroid hy#er#lasia rine ndin"s - H% sometimes #resent - Hemosiderinuria TREATMENT
o $ransfusions for anemia3 washed #+BCs o Oral iron thera#y for I,A
o teroid hormones o Anticoa"ulants
o !arrow trans#lantation is curative
o Ecl0m"b & a humaniGed monoclonal anti%ody that %inds to the human C
com#lement #rotein
o Administered wee/ly5 =88m" IV5 for the rst ) wee/s then 88m" on wee/ then
88m" every ) days thereafter
LABORATOR. TESTS R(0'e L"br"(r Te3(3 Cmle(e Bl4 C'(
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 as
9VAN 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"h num%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"<dL
Hi"her levels of indirect %iliru%in indicate com#romised he#atic function or cholelithiasis and hemolysis
Chan"es in the L,H and erum Ha#to"lo%in levels are the most sensitive "eneral tests %ecause the indirect %iliru%in is not always increased
Cmb3 (e3(
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/ d ue to hemo"lo%inuria5 %ut myo"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 a
dia"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
