B18M02L02-Anemia of Acute and Chronic Blood Loss.docx

7/25/2019 B18M02L02-Anemia of Acute and Chronic Blood Loss.docx

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ANEMIA OF ACUTE AND CHRONIC BLOOD LOSSBLOCK

18

MG Alfeche, MD MODULE2

LECTURE2

December 2, 21!, 8"m#1"m

OUTLINE

I. Overview of Acute and Chronic Blood LossII. Acute Blood Loss

III. Classication of AnemiaIV. Hemolytic AnemiaA. Non-immune Hemolytic Anemia. !icroan"io#athic Hemolytic Anemia

a. $hrom%otic $hrom%ocyto#enic

&ur#ura'. !acroan"io#athic Hemolytic Anemia

a. !arch Hemo"lo%inuria%. $raumatic Cardiac Hemolytic

Anemia(. Hemolytic anemia resultin" from a

chemical or #hysical a"ent). Hemolytic anemia resutin" from

infectious a"entB. Immune Hemolytic Anemia. Autoimmune Hemolytic Anemia

a. *arm +eactin" Anti%odies%. Cryo#athic Hemolytic Anemia

c. Alloimmune Hemolytic ,isease of

the New%orn'. ,ru"-induced Hemolytic Anemia

V. Chronic Blood Loss. Chronic I %leedin"

'. A%normal Va"inal Bleedin"VI. Hy#o#roliferative Anemia

. Iron ,eciency Anemia'. Anemia of +enal ,isease

(. Anemia of Hy#ometa%olic state

/i##ed to#ics

I. &aro0ysmal Noctural Hemo"lo%inuraII. La%oratory $ests

O$ER$IE%

BLEEDING & used to descri%e %lood loss

# Blood loss inside the %ody 1I'(er'"l)# Blood loss outside the %ody 1E*(er'"l)

INTERNAL BLEEDING 2 %lood lea/s out throu"h dama"e to a %lood vessel or or"an

E+TERNAL BLEEDING & occurs either when %lood e0its3

$hrou"h a %rea/ in the s/in

$hrou"h natural o#enin"s3

!outh

Nose 1Nose %leedin"4

Va"ina 1menstruation4

+ectum 1haemorrhoids5 anal se04

ACUTE BLOOD LOSS & A condition in which a #atient 6uic/ly loses a lar"e volume of circulatin"

hemo"lo%in

CHRONIC BLOOD LOSS &A condition wherein the %lood loss develo#s slowly over time and sym#toms

may %e %arely noticea%le and "radually worsen

&a"e 1of 2


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Normal3 #in/ish s/in7 fast ca#illary rell Anemic3 #ale s/in7 slow ca#illary rell

CASE-

A '8 year-old colle"e student was %rou"ht to the

emer"ency room due to a vehicular accident.

&ertinent &.9.3

&ale5 unconscious5 stretcher-%orne

B&: ;8


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&ulmonary

Intracranial Tr"m"

Hemrrh"5e

Me'3(r"l 67

Heml303 & increases erythrocyte destruction

Tr"m"(0c blee40'5

Caused %y inDury# unshot wounds# Crushin" inDuries# &uncture wounds - /nife

Me40c"l C'40(0'3

Hemo#hilia

Intracranial Intra-a%dominal

!enorrha"ia

EBLOOD LOSS CAUSES ANEMIA B. THE FOLLO%ING MECHANISMS-

By the direct loss of red %lood cells

If the %lood loss is #rotracted

,ecreased iron stores

Iron ,eciency Anemia

ACUTE BLOOD LOSS

Blood loss causes anemia in ' mechanisms319 :3(#Hemrrh"50c A'em0"

90ternal- $rauma- O%stetric hemorrha"e

Internal

- astrointestinal %leedin"- +u#tured s#leen- +u#tured ecto#ic #re"nancy- u%arachnoid hemorrha"e

29 Heml303

EOTHER MANIFESTATIONS OF ACUTE BLOOD LOSS-. Chest discomfort

'. Arm or %ac/ discomfort Hemarthrosis(. Nec/ or Daw discomfort

!ulti#le myeloma which may re#resent as stiF nec/). $rou%le %reathin"5 with or without chest discomfort. ?eelin" li"ht-headed or %rea/in" into a cold sweat=. ?eelin" sic/ or discomfort in your stomach

If youn" woman you may consider "ynecolo"ic #ro%lems li/e ecto#ic #re"nancy5ovarian ru#tured cyst

MILD BLOOD LOSS 2 9nhanced o0y"en delivery is achieved3

- $hrou"h chan"es in the O'-H% dissociation curve mediated %y a decreased #H orincreased CO' ;Bhr E


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

1#1!> l33 f (("l bl4 /lme si"ns of vascular insta%ility

o hy#otension

o decreased or"an #erfusion

?=> "c(e bl4 l33 & failure to com#ensate with the usual mechanism of vascular

contraction and chan"es in re"ional %lood @owo #atient remains in su#ine #osition

o #ostural hy#otension

o tachycardia

?@> "c(e bl4 l33 more than ' liters 1avera"e siGed adult4

o H/lem0c Shc

- Confusion- ,ys#nea- ,ia#horesis- Hy#otension- $achycardia

o Imme40"(e /lme rel"ceme'(

ACUTE HEMOL.SIS 2 increased red cell destruction

Sm(m3 f m4er"(e "'em0"-# ?ati"ue# Loss of stamina# Breathlessness# $achycardia

%h"( "re (he 305'3 f Ac(e G"3(r0'(e3(0'"l Blee40'5- Hy#otension 1systolic B& 8mmH"4- $achycardia 1J'8 %#m4- Orthostatic chan"es in B&

- Blood or coFee-"round-li/e material in N$ as#irate

I in ori"in Hematemesis3 vomitin" of %lood HematocheGia3 fresh %lood from stool

THREE CLINICAL:ATHO:H.SIOLOGIC STAGES

OF ACUTE BLOOD LOSS

19 H.:O$OLEMIA

Loss of consciousness

Acute renal failure

# Blood count will not show anemia since H% level is not aFected# +elease of vaso#ressin and other #e#tide caused %y %arorece#tors and stretch rece#tors

Hy#ovolemiawhich #oses a threat #articularly to or"ans

that normally have a hi"h %lood su##ly5 li/e the %rain

&a"e @of 2


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and the /idneys7 therefore5 loss of consciousness and

acute renal failure are maDor threats

HarrisonKs Boo/ of Internal !edicine thedition

29 HEMODILUTION# shift of @uid from the e0travascular to the intravascular com#artment

As an emer"ency res#onse5 %arorece#tors and stretch

rece#tors will cause release of vaso#ressin and other

#e#tides5 and the %ody will shift @uid from the

e0travascular to the intravascular com#artment5

#roducin" H9!O,IL$ION thus hy#ovolemia "radually

converts to anemia

$he de"ree of anemia will re@ect the amount of %lood

lost. If after ( days the hemo"lo%in is5 for e0am#le5 >

"


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and correctin" the cause of the anemia is the

rst #riority and %lood transfusion may not %e

even necessary %ecause the %ody is ada#ted to

the anemia5 with acute %lood loss the reverse is

true %ecause the %ody is not ada#ted to the

anemia5 %lood transfusion ta/es #riority

29 *hile the emer"ency is %ein" confronted5 it is

im#erative to sto# the hemorrha"e and toeliminate its source

Blood loss durin" and immediately after sur"ery5 which

can %e su%stantial 1e.".5 u# to ' L in the case of a radical

#rostatectomy4. Of course with elective sur"ical

#rocedures5 the #atientKs own stored %lood may %e

availa%le 1throu"h #reo#erative autolo"ous %lood

donation45 and in any case5 %lood loss ou"ht to have

%een carefully monitored


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i. ?anconi anemiaii. chwachman syndromeiii. ,ys/eratosis con"enital

%. 9rythroid #ro"enitor cell failurec. ?unctional im#airment of erythroid and other #ro"enitors due to nutritional and

other causes

B. Increased +ed Cell ,estruction. Ac6uireda. !echanical

i. !acroan"io#athic 1!arch hemo"lo%inuria5 articial heart valves4ii. !icroan"io#athic 1,IC5 $$&5 Vasculitis4iii. &arasites and microor"anisms 1malaria5 %artonellosis5 C. welchii4iv. Chemical inDury and com#le0 chemicalsv. &hysical inDury

%. ,ru"-mediated Hemolysisc. Anti%ody-mediated

i. *arm-ty#e autoimmune hemolytic anemiaii. Cryo#athic syndromes 1cold a""lutinin disease5 #aro0ysmal cold

hemo"lo%inuria5 cryo"lo%ulinemia4iii. $ransfusion reactions 1immediate and delayed4

c. Hy#ers#lenismd. +ed cell mem%rane disorders

i. #ur cell hemolysisii. Ac6uired acanthocytosis and ac6uired stomatocytosis

'. Hereditary

a4 Hemo"lo%ino#athies%4 +ed cell mem%rane disordersc4 +ed cell enGyme defectsd4 &or#hyrias

C. Blood loss and %lood redistri%ution

Only way to re#lace %lood loss is %lood transfusion unit of #ac/ed +BC will re#lace "


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+ed %lood cell destruction can occur in the e0travascular

or intravascular s#ace

90travascular Hemolysis

- red %lood cells are #ha"ocytiGed %y

reticuloendothelial cells5 the mem%rane

structure is %ro/en down5 and the hemo"lo%in is

reduced to its essential com#onents- Iron is recovered for trans#ort %y transferrin

%ac/ to the erythroid marrow. $he #or#hyrin rin"

is %ro/en5 and a molecule of car%on mono0ide is

released.- $he remainin" #ortion of the #or#hyrin rin" is

then trans#orted as %iliru%in to the liver for

conDu"ation and e0cretion in %ile.

Intravascular hemolysis

- red cell destruction5 free hemo"lo%in %inds

either to ha#to"lo%in or hemo#e0in or is

converted to methemal%umin.

- $hese #roteins are cleared %y the liver where theheme is %ro/en down to recover iron and

#roduce %iliru%in

Hematolo"y in Clinical &ractice thedition

-&ossi%le causes3

I'fec(0'3 1note3 ,irect Coom%s test is sometimes #ositive in hemolytic anemia due to

infection4

!alaria

Ba%esiosis e#ticemia

Membr"'e 403r4er3

&aro0ysmal nocturnal hemo"lo%inuria 1+are ac6uired clonal disorder of red %lood

cell surface #roteins4

Liver disease

Dr5#0'4ce4 Heml303

I'(r"cr3cl

"r Defec(3

E*(r"cr3cl

"r Defec(3Here40("r Hemo"lo%ino#at

hies

9nGymo#athies

!em%rane-

cytos/eletal

?amilial

hemolytic uremic

syndrome 1H4

&a"e 8of 2


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defectsAc0re4 &aro0ysmal

Nocturnal

Hemo"lo%inuria

1&NH4

!echanical

destruction

1microan"io#athi

c4

$o0ic a"ents

,ru"s

Infectious

Autoimmune

Ge'er"l E*"m0'"(0' "'40ce, "llr

Other #hysical ndin"s #leen may %e enlar"ed7

%ossin" of the s/ull in

severe con"enital casesHemo"lo%in ?rom normal to severely

reduced!CV5 !CH sually increased+eticulocytes IncreasedBiliru%in Increased 1mostly

unconDu"ated4L,H Increased 1u# to 80

normal with intravascularhemolysis4

Ha#to"lo%in +educed to a%sent

NON#IMMUNE HEMOL.TIC ANEMIA

Re4 cell fr"5me'( 3'4rmeMech"'0c"l De3(rc(0' f re4 cell3

!icroan"io#athic hemolytic anemia

!acroan"io#athic hemolytic anemia

Chemical a"ents

Infectious a"ents

Her3le'03m

:"r*3m"l Nc(r'"l Hem5lb0'r0"

MICROANGIO:ATHIC HEMOL.TIC ANEMIA# Intravascular hemolysis caused %y fra"mentation of normal red cells #assin" throu"h

a%normal arterioles# De30(0' f l"(ele(3 "'4 br0'2 the most common cause of microvascular lesions# Chronic and iatro"enic

!icroan"io#athic hemolytic anemias 1!AHAs4

# are a "rou# of #otentially life-threatenin"

disorders characteriGed %y +BC ?ra"mentationand throm%ocyto#enia

# $he +BC fra"mentation occurs intravascularly %y

the mechanical shearin" of +BC mem%ranes as

the cells ra#idly #ass throu"h tur%ulent areas of

small %lood vessels that are #artially %loc/ed %y

microthrom%i dama"ed endothelium# #on shearin"5 +BC mem%ranes 6uic/ly reseal

with minimal esca#e of hemo"lo%in5 %ut the

resultin" fra"ments 1called schistocytes4 are

distorted and %ecome ri"id.# $he s#leen clears the ri"id +BC fra"ments from

the circulation throu"h the e0travascular

hemolytic #rocess

ETIOLOG. AND :ATHOGENESIS-

&a"e Jof 2


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Intravascular coa"ulation5 with de#osition of #latelets and %rin in small arterioles 2 the

common antecedent +ed cells stic/ to %rin and are fra"mented %y force of %lood @ow resultin" in %oth

intravascular and e0travascular hemolysis

UNDERL.ING DISORDERS- Invasive carcinoma

Com#lications of #re"nancy3 #re-eclam#sia5 eclam#sia5 a%ru#tio #lacentae !ali"nant hy#ertension

$$&5 H

,ru"s3 antineo#lastic a"ents5 most often m0(mc0', %ut also include %leomycin5

daunoru%icin in com%ination with cytosine ara%inoside5 cis#latin 1H may occur wee/s ormonths after discontinuin" mitomycin thera#y4

&osttrans#lation of /idney or liver

&ost-allo"eneic or autolo"ous marrow trans#lantation

eneraliGed vascultis associated with immune disorders. 903 L95 #olyarteritis nodosa5

*e"enerKs "ranulomatosis5 scleroderma 1Connective tissue disorders4 LocaliGed vascular a%normalities3 cutaneous cavernous heman"iomas5

heman"ioendothelioma of the liver

THROMBOTIC THROMBOC.TO:ENIC :UR:URA# CharacteriGed %y the #resence of throm%ocyto#enia5 microan"io#athic hemolytic

anemia5 neurolo"ic sym#toms 1headache5 confusion5 seiGure5 #aresis5 dys#ha"ia45 renalinvolvement and fever

# Consistent with severe hemolysis5 mar/edly increased s. L,H5 increased indirect%iliru%in

# !icrosco#ic hematuria and #roteinuria also #resent

rine of #atients with $$&3 tea colored due to increased indirect %iliru%in $ea colored urine can also %e due to #rimary liver disease If there is increased in conDu"ated %iliru%in most li/ely it is caused %y liver disease

$here is diFerent shades of Daudince

o Hemoytic3 #ale yellowo He#atic3 dar/ or dee# yellow

CLINICAL FEATURES- ym#toms and si"ns are related to the #rimary #rocess and to the or"ans aFected %y

the intravascular de#osition of #latelets and %rin Blood lm3 schistocytes5 helmet cells5 trian"ular cells5 s#herocytes7 elevated reticulocyte

count Increased concentrations of #lasma hemo"lo%in5 urine hemo"lo%in5 and hemosiderin

s. L,H increased

Coa"ulation a%normalities due to consum#tion coa"ulo#athy

&a"e 1of 2


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

o u##ortive3 re4 cell (r"'3f30'3 1to maintain ade6uate level of H%4 and l"(ele(

(r"'3f30'31for %leedin" due to throm%ocyto#enia4

MACROANGIO:ATHIC HEMOL.TIC ANEMIA

MARCH HEMOGLOBINURIA

- Acute and self-in@icted- !ild anemia occurs in individuals involved in sustained5 strenous #hysical activity

:ATHOGENESIS- Hemo"lo%inuria may occur from trauma sustained %y intravascular red cells in the feet

of lon" distance runners or in the hands of /arate #ractitioners or in #ersons #layin" thecon"a drums

astrointestinal %leedin" occurs in '8 of lon" distance runners 1usually not enou"h to

cause anemia4

CLINICAL FEATURES- Concentration of H% and Hct are at lower limits of normal

+BCs tend to %e macrocytic

Increased reticulocyte count Hemo"lo%inuria may %e noted for = to ' hours in runners after a race

THERA:.-o +eassure the #atient

o Add cushioned insoles to the shoes

o #orts anemia3 no treatment

A'em0" "l3 ccr3 0' ASTRONAUTS

- Caused %y a decrease in #lasma volume5 followed %y a decrease in erythro#oietinlevels5 and the rate of red cell #roduction. *hen the #lasma volume is restored afterreentry an anemia is evident

TRAUMATIC CARDIAC HEMOL.TIC ANEMIA

- Com#lications of #rosthetic heart valves that lead to tur%ulence and hi"h shear stresseswithin a s#ace enclosed %y a forei"n surface resultin" in red cell fra"mentation andhemolysis

- Cardiac valve disorders5 es#ecially severe aortic or su%aortic stenosis5 may also causehemolysis

CLINICAL FEATURES- Hemolytic anemia is usually mild and com#ensated %ut may %e severe

&resence of throm%o"enicity of non-endothelialiGed surfaces5 which #romote #latelet

throm%osis and em%oliGation

Blood lm3 schistocytes5 helmet cells5 trian"ular cells5 and s#herocytes #resent. mallhy#ochromic cells may %e #resent

&a"e 11of 2


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

#resent ti"mata of iron deciency3 includin" a hi"h unsaturated iron-%indin" ca#acity and a low

serum ferritin ,ecreased #latelet count may indicate #latelet throm%i on valve surfaces

THERA:.-

o +e#lace urinary iron loss with ?eO)o ?or severe anemia re#lacement of #rosthesis

o Blood transfusion

o +ecom%inant 9&O treatment for severe anemia ineli"i%le for reo#eration

HEMOL.TIC ANEMIA RESULTING FROM A

CHEMICAL OR :H.SICAL AGENT- Certain dru"s can induce hemolysis in individuals with a%normalities of erythrocytic

enGymes5 li/e =&, deciency or with an unsta%le H%- Common chemicals3

ARSENIC H.DRIDE

Inhalation of arsenic "as can lead to severe anemia5 hemo"lo%inuria5 and Daundice

LEAD

Lead #oisonin" in CHILDREN- due to in"estion of lead #aint @a/es or chewin" lead-

#ainted o%Dects

Lead #oisonin" in ADULTS- due to industrial e0#osure

Into0ication leads to anemia inhi%ition of heme synthesis modest decrease inred cell life s#an

Inhi%its #yrimidine K-nucleotidaseres#onsi%le for the %aso#hilic sti##lin"

+in"ed sidero%lasts are fre6uently found in the marrow

CO::ER !ay %e induced %y hi"h levels of co##er in #atients hemodialyGed with @uid

contaminated %y co##er tu%in"

Caused %y inhi%ition of several erythrocyte enGymes

%ATER

Administered intravenously5 inhaled in near-drownin"5 or "ainin" access to the

circulation durin" irri"ation #rocedures can cause hemolysis

O+.GEN

HA has develo#ed in #atients receivin" hy#er%aric o0y"enation and in astronauts

e0#osed to 88 o0y"en

INSECT AND ARACHNOID $ENOMS

evere hemolysis may occur in #atients followin" %ites %y %ees5 was#s5 s#iders5

scor#ions

na/e %ites only +A+9L cause hemolysis

HEAT

90tensive %urns may develo# severe HA result of direct dama"e to the red cells

%y heat

DRUGS AND CHEMICALS THAT HA$E BEEN RE:ORTED TO CAUSE CLINICALL.SIGNIFICANT HEMOL.TIC ANEMIA

CHEMICALS DRUGSAniline Amyl nitrate

&a"e 12of 2


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A#iol

,ichloro#ro# 1her%icide4

?ormaldehyde

Hydro0yllamines

Lysol

!ineral s#irits

Nitro%enGene

+esorcin

!e#henesin

!ethylene %lue

Ome#raGole

&entachloro#henol

&henaGo#yridine

alicylaGosulfa#yridine

HEMOL.TIC ANEMIA RESULTING FROM

INFECTIOUS AGENTSMECHANISMSHemolysis may %e caused %y3 ,irect invasion %y infectin" or"anism 1!alaria4

9la%oration of hemolytic to0ins 1C. perfringens)

,evelo#ment of autoanti%odies a"ainst red %lood cells anti"ens 1Mycoplasma pneumoniae)

ETIOLOGIC AGENTS-

Aspergillus

Babesia microti and Babesia divergens

Bartonella bacilliformis

Campylobacter jejuni

Clostridium welchii

Coxsackie virus

Cytomegalovirus

iplococcus pneumoniae

!pstein"Barr virus

!scherichia coli

#aemophilus in$uen%a

#epatitis A

#epatitis B

#erpes simplex virus

#&'

&n$uen%a A

(eishmania donovani

(eptospira ballum andor butembo

M"l"r0" & worldKs most common cause of hemolytic anemia

Mumps virus

M. tuberculosis

M. pneumoniae

*eisseria intracellularis

+arvovirus B,-

+lasmodium falciparum

&a"e 1=of 2


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IMMUNE HEMOL.TIC ANEMIA

Imm'e Heml(0c A'em0"3

$hese can arise throu"h at least two distinct

mechanisms

19 $here is a true autoanti%ody directed a"ainsta red cell anti"en5 i.e.5 a molecule #resent on the

surface of red cells.29 *hen an anti%ody directed a"ainst a certain

molecule 1e.".5 adru"4 reacts with that molecule5

red cells may "et cau"ht in the reaction5

where%y they are dama"ed or destroyed

HarrisonKs Boo/ of Internal !edicine thedition

AUTOIMMUNE HEMOL.TIC ANEMIA

CLASSIFICATION-I. On %asis of serolo"ic characteristics of involved autoimmune #rocess3

A. *arm-autoA% ty#e3 AutoA% ma0imally active at b4 (emer"(re5 (>PCB. Cold-autoanti%ody ty#e3 AutoA% active at tem#erature bel7 (>PCC. !i0ed cold and warm auto-A%s

II. On %asis of #resence or a%sence of underlyin" or si"nicantly associated disorderA9 :r0m"r r 040"(h0c AHAB9 Sec'4"r AHA

. Associated with lym#ho#roliferative disorders 1NHL5Hod"/inKs lym#homa4

'. Associated with the rheumatic disorders(. AssocKd with certain infections

). AssocKd with certain nonlym#hoid neo#lasms 1e0. Ovariantumors4. AssocKd with certain chronic in@ammatory diseases

1e0. lcerative Colitis4=. AssocKd with in"estion of certain dru"s 1methyldo#a4

HEMOL.TIC ANEMIA RESULTING FROM %ARM#REACTING ANTIBODIES

- Caused %y an autoanti%ody directed a"ainst a red cell anti"en- In autoimmune hemolytic anemia 1AHA45 shortened red %lood cell survival result of host

anti%odies that react with autolo"ous +BC- !ost of the #ha"ocytosis 2 mediated red cell destruction ta/es #lace in the s#leen and livere*(r"/"3cl"r heml303

- AHA may %e classied %y the nature of the anti%ody3 M*arm-reactin" A%s have o#timal activity at (>PC

MCold-reactin" A%s show aQnity at lower tem#eratures- %"rm "'(0b4 AHA & most common ty#e- AHA occurs in all a"e "rou#s5 %ut the incidence rises with a"e- !ay %e also classied %y whether an underlyin" disease is #resent 1secondary4 or not

1#rimary or idio#athic4

:r0m"r AHA 2 the autoanti%ody often is s#ecic for a sin"le +BC mem%rane #rotein

su""estin" that an a%%erant immune res#onse has occurred to an autoanti"en or a similarimmuno"en

&a"e 1@of 2


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Anti%ody-coated +BCs are tra##ed %y macro#ha"es #rimarily in the s#leen5 where they

are in"ested and destroyed or #artially #ha"ocytosed and a s#herocyte with similarsurface area is released.

!acro#ha"es have cell surface rece#tors for the ?c #ortion of I" and fra"ments of C(

and C)%. ,irect +BC lysis %y com#lement is unusual in warm anti%ody AHA5 #ro%a%ly as a result

of interference with com#lement activity %y several mechanisms

Sec'4"r AHA # autoanti%ody most li/ely develo#s from an immunore"ulatory defect

ym#toms are usually slow in onset5 %ut ra#idly develo#in" anemia can occur

&.9. may %e normal if the anemia is mild

#lenome"aly is common %ut not always o%served

Blood lm3 #olychromasia 1indicatin" reticulocytosis4 and s#herocytosis

*ith severe cases5 nucleated +BCs5 +BC fra"ments5 and occasionally5

erythro#ha"ocytosis %y monocytes may %e seen !ild neutro#hilia and normal #latelet count occur

E/"'3 3'4rme & rare condition in which %oth immune-mediated +BC and #latelet

destruction occur

B!A3 erythroid hy#er#lasia nconDu"ated hy#er%iliru%inemia often #resent

,ia"nosis of AHA3 re6uires demonstration of immuno"lo%ulin and


16/27

Cold a""lutinins are I"! autoanti%odies that a""lutinate red cells o#timally %etween 8PC

and PC DONATH#LANDSTEINER ANTIBODIES

sually associated with an acute viral syndrome in children 2 common

Com#lement 0ation occurs at hi"her tem#eratures

- $his is classied as eithero &rimary3 chronic cold a""lutin diseaseo econdary3 "enerally as a result of myco#lasma or infectious mononucleosis

- &ea/ incidence3 #rimary


17/27

ALLOIMMUNE HEMOL.TIC DISEASE OF THE

NE%BORN

,enition3- A disease in which there is fetal to maternal transfer of red cells that results in

immuniGation of the mother- $rans#lacental transfer of maternal anti-red cell anti%odies to the fetus shortens the life

s#an of fetal or new%orn red cells- !anifestations3 anemia5 Daundice5 and he#atos#lenome"aly- In severe cases3 anasarca and /ernicterus

9tiolo"y and &atho#hysiolo"y $rans#lacental #assa"e of fetal cells occurs in >= of #re"nancies

If there is %lood "rou# incom#ati%ility %etween mother and fetus5 the chance of

maternal immuniGation increases with the volume of any trans#lacental haemorrha"e Lar"er volume trans#lacental hemorrha"es are more li/ely to occur at delivery or durin"

invasive o%stetric #rocedures $he ris/ of sensitiGation increases with each trimester of #re"nancy and is "reatest

1=4 at delivery &rior %lood transfusion or a%ortions also can immuniGe the mother

*ithout #ro#hyla0is5 immuniGation occurs in >-; of those at ris/ with an +h-#ositive5

ABO-com#ati%le fetus5 and ' of these with ABO-incom#ati%le fetus Ant-, I" readily crosses the #lacenta and leads to a #ositive anti"lo%ulin test and

hemolysis of the infant In ABO haemolytic disease3 themother is usually ty#e O and the fetus is $y#e A or B

Anti-A and Anti-B ordinarily cause mild and rarely severe hemolysis

Clinical ?eatures *ith severe hemolysis5 #rofound anemia leads to hydro#s fetalis 1anasarca caused %y

cardiac failure45 and most such features die in utero *ith milder cases3 hemolysis #ersists until incom#ati%le +BCs or the oFendin" I" is

cleared 1Half-life of I"3 ( wee/s4 !ost aFected infants are not Daundiced at %irth due to trans#lacental trans#ort of

%iliru%in enerally with mild disease5 the %iliru%in #ea/s at day ) or #ost#artum and declines

slowlt thereafter Increased serum %iliru%in-J /ernicterus 1due to de#osition of unconDu"ated %iliru%in in

the %asal "an"lia and cere%ellum If +h-ne"ative3 should %e tested a"ain at '; wee/s "estation %efore +h immuno"lo%ulin

is "iven

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CASE

R.$.5 a ')-year old em#loyee sou"ht consult at the

9.+. due to diGGiness with tea-colored urine

1S4 fever5 1S4 headache5 1S4 #allor

*hat la%oratory tests are you "oin" to re6uestT

?ollow the @owchart

DRUG#INDUCED IMMUNE HEMOL.TIC ANEMIA# ,ru"s #roduce a #ositive direct anti"lo%ulin test and accelerated red cell destruction

Three mech"'03m3 f 4r5#rel"(e4 0mm'l50c 0'r ( re4 cell3 "re rec5'0e4-19 Ha#ten to 8 daysof treatment

# Ceases a fe7 4"3 ( 2 7ee3 once the dru" is sto##ed

MECHANISMS-19 DRUG ADSOR:TION MECHANISM:e'0c0ll0'3, Ceh"l3r0'3, "'4 S(re(mc0'3

Mechanism

- ?irst5 the dru" is nons#ecically adsor%ed to the #atients red cell- econd5 the dru" must %e a%le to elicit an anti%ody res#onse

$he #atient #roduces an I" anti%ody to a dru". *hen

the dru" is ta/en %y the #atient5 the dru" %inds stron"lyto the #atientKs +BCs. $he I" dru" anti%ody %inds to the

dru" attached to the +BCs5 usually without com#lement

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activation.

Because the oFendin" anti%ody is I" and is stron"ly

attached to the +BCs via the dru"5 hemolysis is

e0travascular %y s#lenic macro#ha"es5 which remove

the anti%ody- and dru"-coated +BCs from the circulation

29 TERNAR. COM:LE+ MECHANISMDr5#A'(0b4 T"r5e(#Cell Cmle*# $he mechanism of red cell inDury is not clearly dened# A##ears to %e mediated %y a coo#erative interaction to "enerate a ternary com#le0

involvin" the 4r5 or 4r5#me("bl0(e5 a 4r5#b0'40'5 membr"'e 30(e on thetar"et cell5 and "'(0b45 with conse6uent activation of com#lement

# $he A% attaches to a 'e"'(05e'consistin" of loosely %ound dru" and red cell A"7%indin" of dru" to the tar"et cell is wea/ until sta%iliGed %y the attachment of the A% to%oth dru" and cell mem%rane

# D0rec( "'(05lbl0' (e3( is usually #ositive with com#lement rea"ents

In ternary dru"-induced hemolysis5 I" anti%odies %ind

dru"-e#ito#e com%ination sites5 called neoanti"ens. $he

dru"-e#ito#e-anti%ody com#le0 on the mem%raneactivates com#lement to tri""er acute intravascular

hemolysis5 often with throm%ocyto#enia.

$he dru"s most often im#licated are 6uinidine5

#henacetin5 and sti%o#hen. Hemolysis occurs after short

#eriods of administration or u#on readministration. $he

,A$ detects only com#lement. In the indirect

anti"lo%ulin test usin" rea"ent +BC5 the serum is

reactive in the #resence of the dru".

Imm'e Cmle* Mech"'03m- PI''ce'( B3("'4erQCl'040'e "'4 :he'"ce(0'

ome dru"s can cause an immune hemolytic anemia

even thou"h they do not %ind to +BCs. $hese dru"s5%ound to #lasma #roteins5 stimulate the formation of

com#lement-0in" anti%odies that activate the classical

com#lement #athway. enerated C(% %inds to the +BC5

which leads to intravascular hemolysis of these

0''ce'( b3("'4er3M.

=9 AUTOANTIBOD. MECHANISM !echanism %y which the dru" can induce formation of an autoanti%ody is un/nown

&ositive direct anti"lo%ulin test3 ;-(= of those ta/in" "lh"#me(hl4"

&ositive test develo#s (-= months after the start of thera#y

Less than of those ta/in" al#ha-methyldo#a develo# hemolytic anemia

A%s in the serum or eluted from +BCs react o#timally at (>PC with autolo"ous or

homolo"ous +BCs in the a%sence of dru" As in Autoimmune HA5 these A%s fre6uently react with the +h com#le0

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,estruction of +BCs occurs chie@y %y s#lenic se6uestration of I"-coated +BCs

A dru" induces the #atient to #roduce I" warm-reactive

autoanti%odies a"ainst +BC selfanti"ens. $hese

autoanti%odies react at (>U C5 and the la%oratory

ndin"s are indistin"uisha%le from those in *AIHA.

Hemolysis is e0travascular and is mediated %y

macro#ha"es

#redominantly in the s#leen.

Me(hl4"#I'4ce4 ;A(0mm'e) Mech"'03mMe(hl4" "'4 rel"(e4 4r53 ;Al4me(, L#4")- (re"(me'( f her(e'30'

An induced inhi%ition of $-su##ressor allowin"

uninhi%ited autoanti%ody #roduction %y B cells. ,es#ite

dru" withdrawal5 anti%odies may remain for months

A3 $he anti%ody attaches only to the dru"5 which is

ti"htly %ound to the red %lood cell 1+BC4 mem%rane

1#enicillin ty#e4

B3 $he anti%ody attaches to a neoanti"en created %y

com#onents of %oth the dru" and the +BC mem%rane

16uinidine


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,iGGiness or li"htheadedness

&allor


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# De/elme'("l 3("5e3 f Ir' Dec0e'c-

IRON DE:LETION 2 tora"e iron decreased or a%sent

IRON DEFICIENC. 2 stora"e iron decreased or a%sent with low serum iron

concentration and transferrin saturation

IRON DEFICIENC. ANEMIA 2 stora"e iron decreased or a%sent5 low serum iron

concentration and transferrin saturation5 and low hemo"lo%in level and reducedhematocrit

STAGES OF IRON DEFICIENC.A9 NEGATI$E IRON BALANCE

- ,emands for 1or losses of4 iron e0ceed the %odyKs a%ility to a%sor% iron from the diet- Causes3

Blood loss 1"reater than 8-'8 ml +BCs days

Oral or IV


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?or sym#tomatic elderly #atients with severe iron deciency anemia and

cardiovascular insta%ility

+eserved for those with sym#toms of anemia5 cardiovascular insta%ility5 and

continued and e0cessive %lood loss from whatever source5 and those who re6uireimmediate intervention

ANEMIA OF RENAL DISEASE

# Chronic renal failure is usually seen with moderate to severe hy#o#roliferative anemia# Normocytic5 normochromic +BCs# ,ecreased reticulocytes# ,ue to inade6uate amounts of erythro#oietin and reduction in red cell survival# Normal serum iron5 $IBC5 and ferritin levels

ANEMIA IN H.:OMETABOLIC STATES# &rotein malnutrition causes mild to moderate hy#o#roliferative anemia# +elease of erythro#oietin from the /idney is sensitive to the need for O'# 9ndocrine deciency states3 related to the eFects of andro"en and estro"en# Tre"(me'(-$ransfusions and 9&O

This topic was skipped by doc:

:ARO+.SMAL NOCTURNAL HEMOGLOBINURIA

DEFINITION- An ac6uired hemato#oietic stem cell disorder characteriGed %y a deciency of

#hos#hatidylinositol-anchored #roteins on the surface of hemato#oietic cells- $his leads to com#lement-mediated intravascular hemolysis- $he only haemolytic anemia caused %y an intrinsic defect of the red cell that is ac6uired

E:IDEMIOLOG.- ame fre6uency in men and women- &revalence is to #er million

- No evidence of inherited susce#ti%ility- !edian survival3 ;-8 years- !ay evolve into a#lastic anemia and &NH may manifest itself in #atients who #reviously

had a#lastic anemia- -' -J Acute !yelo"enous Leu/emia

DIAGNOSIS $he classic a%normality is increased sensitivity to com#lement-mediated lysis of

erythrocytes5 detected %y diFerent tests- Acid hemolysis test- ucrose hemolysis test- C,- ne"ative 1&roduct of &I-A "ene4

$he disorder is a conse6uence of somatic mutations which cause an error in synthesis of

the "lycosyl#hos#hatidylinositol 1&I4 anchor ,eciencies in several &I-anchored mem%rane #roteins5 such as decay acceleratin"

factor5 C, 5 C, ;5 C, =5 C, ) have %een identied &I-A "ene 1#hos#hatidylinositol "lycan class A3 -lin/ed "ene which is re6uired for an

early ste# in &I %iosynthesis

CLINICAL FEATURES Nocturnal hemo"lo%inuria is uncommon

Hemo"lo%inuria occurs irre"ularly in most #atients5 #reci#itated %y a variety of events3

infection5 sur"ery5 or contrast dye inDection &atients have chronic haemolytic anemia5 which may %e severe

!odest s#lenome"aly in some #atients

&ancyto#enia is often #resent

Iron deciency as a conse6uence of iron loss in the urine

Bleedin" may occur secondary to throm%ocyto#enia

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Thrmb303 03 rm0'e'( fe"(re

- Venous throm%osis occur fre6uently- Arterial throm%osis also occur- Budd-Chiari syndrome or #ortal vein throm%osis- &ulmonary hy#ertension may develo# secondary to throm%osis in the #ulmonary

microvascular &re"nancy in &NH #atients may %e associated with "br(0' "'4 /e'3

(hrmbembl03m Re'"l m"'0fe3("(0'3 0'cl4e

- Hy#osthenuria- e0cretion of urine of low s#ecic "ravity- A%normal tu%ular function- Acute and chronic renal failure

Nerl50c m"'0fe3("(0'3

- Headache- Cere%ral venous throm%osis uncommon

Clinical ym#toms of &NH3 A $riad of Clinical ?eatures

. Ac6uired cor#uscular haemolytic anemia- Chronic hemolysis or acute hemolysis crises

- Hemosiderinuria5 Iron deciency'. $hrom%o#hilia

- Aty#ical throm%osis3 Budd-Chiari syndrome5 #ortal vein throm%osis5 mesenterialthrom%osis5 cere%ral throm%osis

(. Bone marrow failure- $hrom%ocyto#enia and


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the test documents anemia5 leu/ocyte counts5 and diFerential counts

&latelet count3 e0clude an underlyin" infection or hematolo"ic mali"nancy. $he #latelet

count is within the reference ran"e in most haemolytic anemias $hrom%ocyto#enia can occur in L95 CLL5 and !icroan"i#athic haemolytic anemia.

$hrom%ocyto#enia associated with a #ositive direct Coom%s test result is /nown as9VAN N,+O!9

Re4 bl4 cell I'40ce3 ,ecreased !CV and !CH3

# !icrocytic hy#ochromic anemia3 chronic intravascular hemolysis 1&NH4 Hi"h !CV3 macrocytic anemia

# sually due to me"alo%lastic anemias %ut can occur in liver disease. A hi"hnum%er of reticulocytes also may cause a hi"h !CH

A hi"h !CH and !CHC3 s#herocytosis

Increased +,* study

# !easure of anisocytosis which is li/ely in haemolytic anemia

LABORATOR. TESTS FOR HEMOL.SIS

Serm H"(5lb0' m54L !ost sensitive test for +BC destruction

A "lyco#rotein synthesiGed mainly in the liver

e6uesters free H% released from hemolyGed +BC-J trans#orted %y macro#ha"es to

the liver-J heme %ro/en down to %iliru%in

L"c("(e 4eh4r5e'"3e Increased 1L, J''4

L, occurs in the cyto#lasm of all cells

Increased in all haemolytic anemias

I'40rec( b0l0rb0' nconDu"ated %iliru%in is a criterion for hemolysis5 %ut is not s#ecic %ecause an

elevated %iliru%in is also may indicate il%ert ,isease *ith hemolysis5 the level of indirect %iliru%in usually is less than ) m"


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D0rec( "'4 0'40rec( "'(05lbl0' ;Cmb3) (e3(3

1a4 $he direct anti"lo%ulin test 1,A$4 is #erformed %y

incu%atin" the #atientKs washed red %lood cells 1+BCs4

with a rea"ent that contains anti%odies to I"5 C(

com#lement or %oth 1nons#ecic rea"ent4. A""lutination

of the +BCs indicates that there is either I" or C(5

res#ectively5 %ound to the +BC mem%rane

1%4 $he indirect anti"lo%ulin test is #erformed %y

incu%atin" a normal donorKs washed +BCs with the

#atientKs serum in the #resence of a rea"ent that

contains anti%odies to I"5 C( or %oth. A""lutination of

the +BCs indicates the #resence of an anti%ody5 or

com#lement5 directed toward an +BC cell surface

anti"en in the #atientKs serum

Sec0c 3(40e3 40"5'3e4 b h03(r, :E, er0her"l 3me"r "'4 (her l"b '40'53

,A$ result is usually #ositive in autoimmune haemolytic anemia5 %ut it may %e occasionally

ne"ative in this disorder

rine free H% test reveals hemo"lo%inuria5 which occurs with intravascular hemolysis when the amount of

free H% e0ceed the availa%le ha#to"lo%in. rine may %e dar/ due to hemo"lo%inuria5 %utmyo"lo%inuria #or#hyria5 and other conditions can also cause dar/ urine

rine hemosiderin may su""est intravascular hemolysis. Hemosiderin is detected in s#un urinary sediment

as an iron stain in slou"hed renal e#ithelial cells

+BC survival chromoim- survival is rarely used %ut it can denitely demonstrate a shortened +BC survival 1hemolysis4.

$his test is ordered when the clinical history and la%oratory studies cannot esta%lish adia"nosis of hemolysis

Cold a""lutin titer A hi"h titer of anti-I anti%ody may %e found in myco#lasmal infections and a hi"h titer

of anti-I anti%ody may %e found in hemolysis associated with infectious mononucleosis.An anti-& cold a""lutin may %e seen in &aro0ysmal Cold Hemo"lo%inuria

LALUMA LAM:REA LUCES MOLINA

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B18M02L02-Anemia of Acute and Chronic Blood Loss.docx