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 ANEMIA OF ACUTE AND CHRONIC BLOOD LOSS

 ANEMIA OF ACUTE AND CHRONIC BLOOD LOSS

BLOCK BLOCK 1818 MG Alfeche, MD

MG Alfeche, MD MODULEMODULE

2 2 LECTURE LECTURE 2 2 December 2, 21!, 8"m#1"m December 2, 21!, 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.. CCllaassssiiccaattiioon 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,eccieiencncy 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

(2)

 Normal3 #in/ish s/in7 fast ca#illary Normal3 #in/ish s/in7 fast ca#illary rellrell

 Anemic3 #ale s/in7 slow ca#illary rellAnemic3 #ale s/in7 slow ca#illary rell

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 lefthallow %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 @uidstart on IV @uids

 +e6uest for CBC5 Chest ray5 AB5 +e6uest for CBC5 Chest ray5 AB5 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 1ive &ac/ed +BC41ive &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. uddudden5en5 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

decicienency 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/03 bl4 l33 Ob/03 bl4 l33

astrointest

(3)

&ulmonary Intracranial Tr"m"

Hemrrh"5e Me'3(r"l 67

Heml303 & 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 ,eciency Anemia

ACUTE BLOOD LOSS

Blood loss causes anemia in ' mechanisms3 19 :3(#Hemrrh"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 Heml303

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' ;Bhr E<ec()

- In acute %lood loss5

• Hy#ovolemia dominates

&a"e = of 2 Me40c"l C'40(0'3

(4)

• Hematocrit and hemo"lo%in levels do not re@ect the volume of %lood lost

 1#1!> l33 f (("l bl4 /lme si"ns of vascular insta%ility

o hy#otension

o decreased or"an #erfusion

 ?=> "c(e bl4 l33 & 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 bl4 l33  more than ' liters 1avera"e siGed adult4

o H/lem0c Shc  - Confusion - ,ys#nea - ,ia#horesis - Hy#otension - $achycardia

o Imme40"(e /lme rel"ceme'(

 ACUTE HEMOL.SIS 2 increased red cell destruction Sm(m3 f m4er"(e

"'em0"-# ?ati"ue

# Loss of stamina # Breathlessness #  $achycardia

%h"( "re (he 305'3 f Ac(e G"3(r0'(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

(5)

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"

(6)

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

Hl 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

'. Articially modied 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 inltration

iv. &ostchemothera#y '. Hereditary

(7)

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 articial 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" /lme

HEMOL.TIC ANEMIA

-is anemia due to heml3035 the a%normal %rea/down of +BCs either in the %lood vessels 10'(r"/"3cl"r heml303) or elsewhere in the %ody ;e*(r"/"3cl"r heml303)9

-It has numerous #ossi%le causes5 ran"in" from relatively harmless to life-threatenin". $he "eneral classication of hemolytic anemia is either "c0re4 or 0'her0(e4

(8)

+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 403r4er3

• &aro0ysmal nocturnal hemo"lo%inuria 1+are ac6uired clonal disorder of red %lood cell surface #roteins4

• Liver disease ⇒ Dr5#0'4ce4 Heml303 I'(r"cr3cl "r Defec(3 E*(r"cr3cl "r Defec(3 Here40("r Hemo"lo%ino#at hies 9nGymo#athies !em%rane-cytos/eletal ?amilial hemolytic uremic syndrome 1H4

(9)

defects Ac0re4 &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, "llr

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'4rmeMech"'0c"l De3(rc(0' f re4 cell3 !icroan"io#athic hemolytic anemia

!acroan"io#athic hemolytic anemia Chemical a"ents

Infectious a"ents Her3le'03m

:"r*3m"l Nc(r'"l Hem5lb0'r0" MICROANGIO:ATHIC HEMOL.TIC ANEMIA

# Intravascular hemolysis caused %y fra"mentation of normal red cells #assin" throu"h a%normal arterioles

# De30(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

(10)

  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(mc0', %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

(11)

TREATMENT-o !ana"ement of the #rimary #rocess

o u##ortive3 re4 cell (r"'3f30'3 1to maintain ade6uate level of H%4 and l"(ele(

(r"'3f30'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 ccr3 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

(12)

 Increased reticulocyte count5 increased s. L,H5 increased #lasma H%5 urine hemosiderin #resent

 ti"mata of iron deciency3 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 ?eO)

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 =&, deciency 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

(13)

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 andor 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

(14)

IMMUNE HEMOL.TIC ANEMIA

Imm'e Heml(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 b4 (emer"(re5 (>PC B. Cold-autoanti%ody ty#e3 AutoA% active at tem#erature bel7 (>PC C. !i0ed cold and warm auto-A%s

II. On %asis of #resence or a%sence of underlyin" or si"nicantly 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"/"3cl"r heml303

- AHA may %e classied %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 "'(0b4 AHA & most common ty#e

- AHA occurs in all a"e "rou#s5 %ut the incidence rises with a"e

- !ay %e also classied %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#ecic 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

(15)

  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'4rme & 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 Glccr(0c043 2 6uic/ly slow or sto# hemolysis in '<( of #atients

o ' will achieve a com#lete remission

o Sle'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%ody3 cl4 "55l(0'0'3 and D'"(h# L"'43(e0'er "'(0b40e3

- $he com#lement system #lays a maDor role in red cell destruction

 COLD AGGLUTININ#MEDIATED AUTOIMMUNE HEMOL.TIC ANEMIA

(16)

⇒ 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 classied 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#ercial 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' "( (emer"(re3 3"ll bel7 =C & (he ccr 0' er0her"l c0rcl"(0' "'4 0' cl4 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

# &B3 autoa""lutination5 #olychromasia5 s#herocytosis #  $hera#y3 /ee#in" the #atient warm

(17)

ALLOIMMUNE HEMOL.TIC DISEASE OF THE NE%BORN

,enition3

- 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

(18)

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 4r5#rel"(e4 0mm'l50c 0'r ( re4 cell3 "re

rec5'0e4-19 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#43e 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( "'(05lbl0' (e3(  #ositive  heml(0c "'em0"- occurs after > to 8 days of treatment

# Ceases a fe7 4"3 ( 2 7ee3 once the dru" is sto##ed

MECHANISMS-19 DRUG ADSOR:TION MECHANISM

 :e'0c0ll0'3, Ceh"l3r0'3, "'4 S(re(mc0'3 Mechanism

- ?irst5 the dru" is nons#ecically 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

(19)

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

 Dr5#A'(0b4 T"r5e(#Cell Cmle*

#  $he mechanism of red cell inDury is not clearly dened

# A##ears to %e mediated %y a coo#erative interaction to "enerate a ternary com#le0 involvin" the 4r5 or 4r5#me("bl0(e5 a 4r5#b0'40'5 membr"'e 30(e on the tar"et cell5 and "'(0b45 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( "'(05lbl0' (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 Cmle* Mech"'03m- PI''ce'( B3("'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'( b3("'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" "lh"#me(hl4"

 &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

(20)

 ,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(hl4"#I'4ce4 ;A(0mm'e) Mech"'03m

Me(hl4" "'4 rel"(e4 4r53 ;Al4me(, L#4")- (re"(me'( f her(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 1astric5 ,uodenal4

• !ali"nancy 1Colonic5 +ectal4 • astritis

# S05'3 "'4 3m(m3 "re le33 b/03 • ?ati"ue<easy fati"a%ility<loss of ener"y • *ea/ness

(21)

• ,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 deciency is usually caused

%y 5"3(r0'(e3(0'"l bl4 l33. 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 deciency. 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 # M3( cmm' "'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' Dec0e'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(hr0e(0' re3'3e ( "'em0" 1Anemia due to renal disease5 In@ammation5 Cancer5 Hy#ometa%olic states4

 Chronic %lood loss can lead to Iron ,eciency Anemia IRON DEFICIENC. ANEMIA

# !ost common chronic maladies in humans

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# De/elme'("l 3("5e3 f Ir'

Dec0e'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 decit is remedied %y mo%iliGation of iron from +9 stora"e sites

 Me'rrh"50" & most common cause of iron deency in women

 G"3(r0'(e3(0'"l blee40'5 & most common cause of iron deciency 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!

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?or sym#tomatic elderly #atients with severe iron deciency 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 deciency states3 related to the eFects of andro"en and estro"en # Tre"(me'(- $ransfusions and 9&O

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:ARO+.SMAL NOCTURNAL HEMOGLOBINURIA DEFINITION

- An ac6uired hemato#oietic stem cell disorder characteriGed %y a deciency 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

 ,eciencies in several &I-anchored mem%rane #roteins5 such as decay acceleratin" factor5 C, 5 C, ;5 C, =5 C, ) have %een identied

 &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 deciency as a conse6uence of iron loss in the urine

 Bleedin" may occur secondary to throm%ocyto#enia

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Thrmb303 03 rm0'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 "br(0' "'4 /e'3 (hrmbembl03m

Re'"l m"'0fe3("(0'3 0'cl4e

- Hy#osthenuria- e0cretion of urine of low s#ecic "ravity - A%normal tu%ular function

- Acute and chronic renal failure Nerl50c 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 deciency

'. $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 Ecl0m"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"br"(r Te3(3 Cmle(e Bl4 C'(

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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 as

9VAN N,+O!9 Re4 bl4 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

Serm H"(5lb0'  m54L

!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 4eh4r5e'"3e

 Increased 1L, J''4

 L, occurs in the cyto#lasm of all cells

 Increased in all haemolytic anemias I'40rec( b0l0rb0'

 nconDu"ated %iliru%in is a criterion for hemolysis5 %ut is not s#ecic %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

Cmb3 (e3(

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D0rec( "'4 0'40rec( "'(05lbl0' ;Cmb3) (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#ecic 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

Sec0c 3(40e3 40"5'3e4 b h03(r, :E, er0her"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 denitely 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

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Figure

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References