1

!"#$%&' )* + Extiinsic Befects Leauing to

Incieaseu Eiythiocyte
Bestiuction - Non-Immune
Causes

,-.-/01 23-/34-56


789':#;<8:$#%"89 =&>:?@%89 0;&>8#
! Aka NABA
! uioup of uisoiueis chaiacteiizeu by /A!
B'#<>&;%#%8:;, "&>:?@C8C
! The fiagmentation occuis as the cells
pass by small vessels. The RBC
membiane is sheaieu mechanically by
miciothiombi oi uamageu epithelium.
0pon sheaiing the RBC membiane
quickly ieseals foiming C9"8C%:9@%&C.
! These schistocytes aie scieen in the
spleen anu hemolyzeu extiavasculaily
! D"& $'&C&;9& :B C9"8C%:9@%&C :; %"&
$&'8$"&'#? E?::F C>&#' 8C #
9"#'#9%&'8C%89 B&#%G'& :B 70=0
! Becieaseu BgB, haptoglobin. Bematociit
! Incieaseu Retic ct, seium unconjugateu
biliiubin, uiine uiobilinogen
! Nay also see Belmet cells anu
miciospheiocytes.













! 0nuei Nicioangiopathic, the conuition is
teimeu as D"':>E:%89
>89':#;<8:$#%"@ to uesciibe when the
NABA is uue to B:'>#%8:; :B %"':>E8
8; %"& >89':H#C9G?#%G'&
! Thiombotic Nicioangiopathy incluues..
1. Thiombotic thiombocytopenic
puipuia
2. Bemolytic uiemic synuiome
S. Bemolysis, elevateu livei enzymes,
low platelet count (BELLP)
4. Bisseminateu intiavasculai
coagulation
Thiombotic Thiombocytopenic Puipuia
! Elevateu seium LB, WBC Count (left shift
since WBCs aie immatuie), seveie
thiombocytopenia (less than 2u*1u
9
L)
BgB conc less than 1ugul.
! Appeaiance of polychiomasia anu
nRBCs
! Pathophysiology is the '&?&#C& :B H:;
58??&E'#;F B#9%:' fiom vasculai
enuolethial cells. The long vWF binu to
platelets anu clog small bloou vessels
leauing to the foimation of thiombi.
! Nay be acquiieu oi familial
1. Acquiieu
Extiinsic Bemolytic
Anemia
non-immune
Nicioangiopathic
Anemia
Nacioangiopathic
Anemia
Bemolytic Anemia
causeu by
Infectious Agents
immune
see chaptei 2S
Belmet
cells
Niciospheiocytes
2
! I8H8F&F 8;%: C&9:;F#'@ :' ;:;
C&9:;F#'@
! Seconuaiy is associateu with stem cell
tiansplantation, piegnancy, systemic
infections, uisseminateu cancei, uiugs,
autoimmune uisoiueis
! Non seconuaiy is aka iuiopathic TTp.
0sually uue to ueficiency in vWF known
as uisentegiin-like anu metallopiotease
uomain with thiombospouin type1
motifs 1S oi aka ABANTS 1S
! 0nuei noimal conuition, ABANTS 1S
cleave the long vWF to smallei
segements pieventing excessive platelet
aggiegation anu ultimately
miciothiombi foimation.
! D: %'&#% %"& F&B898&;9@J <8H& B'&C"
B':K&; $?#C># %: $#%8&;%L
2. Familial TTPs
! Raie uisoiueis uue to >G%#%8:; 8; %"&
0I07DM NO <&;&
Bemolytic 0iemic Synuiome (B0S)
! Two types B+ B0S anu atypical B0S
! B+ B0S pieceueu bu an episoue of
gastioenteiitis often with bloouy
uiaiihea
! Atypical B0S have no anteceuent
uiaiihea
1. B+ B0S
! !#GC&F E@ - !:?8 PNQR =R
! The E Coli ielease Shiga Toxins which
inteiact with enuothelial cells anu iesult
to cell uisiuption anu foimation of fibiin
clot.
2. Atypical
! 0ncontiolleu complement pathway uue
to mutation in Factois B,I,B ; membiane
cofactoi piotein, thiombomouulin
BELLP Synuiome
! 7:C%?@ F&H&?:$C 8; O
'F
%'8>&C%&'
! !:>$?89#%8:; 8; $'&<;#;9@
! =&>:?@C8CJ &?&H#%&F ?8H&' &;K@>&C
S1I #;F 0MDTJ ?:U $?#%&?&% 9:G;%
! Exact pathogenesis is unknown
! If piothiombin time anu the paitial
thiomboplastin time aie within the
iefeience iange helps uistinguish BELLP
fiom BIC
! 7:'%#?8%@ %: >:> 8C OVQW
! 7:'%#?8%@ %: B&%GC 8C X V)*W
Bisseminateu Intiavasculai Coagulation
! Chaiacteiizeu by the wiuespieau
activation of hemostatic system
! Piothiombin time anu paitial
thiomboplastin time aie piolongeu.
Level of B uimei is incieaseu to
uistinguish BIC
7#9':#;<8:$#%"89 =&>:?@%89 0;&>8#
1. Tiaumatic Caiuiac BA
! !#; :99G' 8; $#%8&;%C U8%" $':C%"&%89
9#'F8#9 H#?H&
! Platelet count is noimal while LB,
inuiiect bili, LB anu plasma BgB aie
incieaseu.
! Suigical iepaii oi piosthesis
ieplacement
! Bemoglobinuiia anu Bemosiueiunia
2. Exeicise - Inuuce Bemoglobinuiia
! Becieaseu level of seium haptoglobin
! Incieaseu level of fiee plasma BgB
! Bemoglobinuiia aftei exeicise
=&>:?@%89 4;B&9%8:;C !#GC&F E@ 4;B&9%8:GC
0<&;%C
NL Nalaiia
! uenus Plasmouium Species
! Falcipaium
! vivax
! 0vale
! Nalaiiae
! Knowlesi
! Common in Afiica, SEA

S
Life Cycle
1. Bite of an infecteu female Anopheles
misquito
2. Spoiozoites invaue hepatic paienchymal
cells to begin exoeiythiocytic
schizogony
S. Aftei S-16 uays, cells iuptuie ieleasing
meiozoites
4. Neiozoites invaue RBCs in ciiculation
thus beginning eiythiocytic schizogony
S. Neiozoite giows into a iing foim which

6. then giows to an matuie schizont with
meiozoites. Paiasitic cycles iecui at
iegulai inteival
7. Some meiozoites entei RBCs to foim
gametocytes which is the ingesteu by an
uninfecteu female anopheles
8. The gametocytes eventually uevelop into
oocyst in salivaiy glanu ang seciete
spoiozoites.
Pathogenesis




! No infection -Nay immunity ie. sickle
cell anemia*
! Asymptomatic anemia - no symptoms
but malaiia is piesent in bloou
! 0ncomplicateu malaiia - has symptoms
anu paiasite but no oigan uysfunction
! Seveie malaiia - has symptoms,
paiasite(hypeipaiasitemia) anu oigan
uysfunction
! Clinical outcome is uepenuent on
uiffeient factois such as paiasitic
(specie, numbei, multiplication iate,
viiulence, uiug iesistance) anu host
(age, immunity, piegnancy, genes, social
factois)
! Cause of anemia in malaiia
1. Biiect lysis of infecteu RBC
uuiing schizogony
2. Immune uestiuction of RBC (both
infecteu anu non ineffective) in
spleen
S. Inhibition & ineffective
eiythiopoesis
*both infecteu anu non infecteu RBCs
aie uestioyeu kasi the paiasite sheu
non self pioteins to bloou anu the
pioteins binu to the RBC membiane
of healthy cells.
! Nalaiial paiasites metabolize
hemoglobin foiming hemozoin. When
cell lysis occuis anu hemozoin is
ieleaseu, it tiiggeis an inflammatoiy
iesponse
! IR incluues TNF a (piomote
inflammation) anu Inteifeion gamma
(incieaseu NBC expiession).
! Incieaseu amounts of TNF u anu INF y
iesults to inhibition of eiythiopoesis.
! IL 6 is also incieaseu anu stimulates
hepciuin piouuction which uecieases
iion available to RBC. ( Note: Bepciuin is
also an Acute Phase Reactant anu with
haptoglobin ueny bacteiia of Fe)
! P falcipaium auheies to enuothelial cells
of in the miciovasculatuie of oigans
which obstiucts the bloou vessel anu
piotects the paiasite fiom the spleen.
Nalaiial
Pathogenesis
no infection
asymptomatic
paiasitemia
uncomplicateu
malaiia
seveie malaiia
Clinical outcome of infecteu
mosquito
4
Pathogenesis of some species of
Plasmouium
! vivax anu 0vale -> ieticulocytes
! Nalaiiae -> oluei RBCs
! Falcimpaium anu knowlesi -> all RBCs
! P vivax neeu Buffy antigens in RBC so
Buffy negative people aie immune to
vivax
Biagnosis
! 0se Wiight uiemsa stain
! Shoulu make 2 thin anu 2 thick smeais
! Thick smeais concentiate the paiasites
initial scieening anu staineu with
Wiights uiemsa without methanol
fixation
! Thin smeais aie useu foi specie
uiffeientiation anu uet. of paiasitemia.
Staineu aftei methanol fixation
! A negative iesult foi a single set uoes
not confiim absence of paiasite.
! Fluoiescent Bes may be useu to uetect
paiasite infection
! Noleculai baseu test to uiffeientiate
specie
! Bipstick type iapiu antigen test
Baseu on the uetection of P
falcipaium anu Plasmouium
aluolase
Tieatment
! Choloioquine oi hyuioxychloioquine
except foi vivax anu falcipaium
! 0se insteau atovaquone-pioguanil
! Piimaquine may eiauicate hypnozoites
in livei




























S

2. Babesiosis
! Tick tiansmitteu uisease
! B micioti is most common
! 0iiginally causeu Nantucket fevei
! 0thei species incluue Buncani,
Biveigens, venatoium
! Noitality iate is less than 1u%
! Symptoms incluue fevei anu iespiiatoiy
flu like symptoms
Biagnosis
! 0se Wiight uiemsa thin smeai
! Bec hemoglobin, haptoglobin
! Inc ietic ct
! Biliiubinemia, Leukemia,
! Thiombocytopenia, hemoglobinemia
! Appeai as tetiaus insiue RBC
! Ring foim may be iounu, ovoiu,
amoeboiu with uaik puiple cytoplasm,
minimal amt of cytoplasm suiiounuing a
blue cytoplasm
! PCR methous foi speciation
! Bistinguisheu fiom p falcipaium uue to
pleomoiphism of theii iing foims
Tieatment
! Combination theiapy with
azithiomycinatovaquone
clinuamycinquinine

S. Clostiiuial Sepsis
! Causeu by Clostiiuium peifiinges
! C. peifiinges piouuce u toxin with
phospholipase C anu sphyngomyelinase
which hyuiolase RBC membianes
! Nay tiiggei BIC anu ienal failuie
4. Baitonellosis
! Tiansmitteu by female sanufly
! Causeu by Baitonella bacillifoimis
! 2 stages
" Stage 1 - acute hemolytic anemia
" Stage 2 - chionic veiiuga stage
chaiacteiizeu by skin lesions anu
waits
Biagnosis
! Naue by bloou cultuie
! Wiight uiemsa staineu peiipheial bloou
smeai
! Iniuiiect immunofluoiescent antibouy
=&>:?@%89 0;&>8# 9#GC&F E@ :%"&' /A!
4;YG'@
1. Biugs
! Cause oxiuative uenatuiation of
Bemoglobin anu foimation of
Nethemoglobin anu Beinz bouies
2. venom
! Bisiupt oi alteiation of RBC membiane
! Fiom contact with snakes, spiueis, bees
anu wasps
S. Extensive buins
! Waiming to 49
o
C in vitio inuuces RBC
fiagmentation anu buuuing
! Schistocytes, spheiocytes anu
miciospheiocytesaie also obseiveu
! Cleai within 24 his