P"thology RBC

Gener&l Anemi&
– We&kness, f&tigue, dyspne&, p&le conjunctiv& &nd skin, he&d&che, &ngin&, &
further coron&ry &rtery dise&se issues.
– Hb, Hct &nd RBC count &re the f&ctors th&t &re used for RBC m&ss
determin&tion.
– Anemi& definition: Hb less th&n 13.5 g/dl in m&les, Hb lower th&n 12.5 g/dl in
fem&les.
– Anemi& c&n be b&sed on MCV (Me&n curpuscul&r volume) &s Microlytic
(MCV less th&n 80), Normocytic (MCV 80-100), or m"crolytic (MCV > 100).

Microcytic "nemi"s
- MCV < 80, RBC &re sm&ll. It occurs bec&use of &n “extr& division” (since &s
they divide from erythrobl&sts they get sm&ller), due to decre&sed production of
Hb, so RBC “try” to divide once &g&in to compens&te for l&ck of hemoglobin.
– Hemoglobin: Heme (Iron &nd protoporphyrin) + globin.
– Deficiency of Iron: Low heme -> Low Hb -> microcytic &nemi&.
– Anemi& of chronic dise&se: Iron is locked in m&croph&ges &nd un&v&il&ble for
use. -> low heme -> low Hb -> microcytic &nemi&.
– Siderobl&stic &nemi&: Low protoporphyrin -> low heme -> Low hemoglobin ->
microcytic &nemi&.
– Th&l&sesmi&: Decre&se production of the globin ch&in -> decre&sed
hemoglobin -> microcytic &nemi&.
Iron Deficiency Anemi&
– Decre&se levels of Iron, most common nutrition&l deficiency in the world &nd
most common &nemi&.
– Iron is consumed in Heme (me&t derived) &nd non-home (veget&bles). Heme
form is more re&dily &bsorbed, in the duodenum. Enterocytes tr&nsport iron
into blood vi& ferroportin, which is the tr&nsporter. In the blood it is bound to
Tr"nsferrin which will tr&nsport it to the liver &nd bone m&rrow m&croph&ges
for stor&ge. Stored intr&cellul&r iron is bound to ferritin.
– There is gener&lly no w&y for the body to remove iron.
– L&b me&surements of iron: Serum Iron (how much iron in the blood), TIBC
(tot&l iron binding c&p&city, How m&ny tr&nsferrin is in the blood), %
S&tur&tion, Serum ferritin (how much is in stor&ge).
– Deficiency c&n be c&used by diet&ry l&ck or blood loss. Inf&nts get it vi&
bre&st feeding since milk doesnʼt cont&ins iron. in children it &rises if thereʼs &
poor diet. Adults get it vi& peptic ulcer dise&se or pregn&ncy (m&les) &nd in
elderly &re common polyps &nd c&rcinom&, &nd hookworm in developing
world.(nic&tor &nd encylosthem&). M&lnutrition, m&l&bsorption, g&strectomy
 (Fe2+ goes into the body, m&int&ined in &cidity, decre&sed &cid bec&use of
g&strecotmy, less iron is in Fe2+ st&te &nd we c&nʼt &bsorb it. ) c&n &lso be
c&uses.
– St&ges of iron deficiency :1) Stor&ge iron is depleted (ferritin depleted, liver
tries to cre&te more tr&nsferrins to incre&se irons so when ferritin is down,
TIBC will be &ctu&lly up.), 2) serum iron is depleted, 3) normocytic &nemi&
(very e&rly ph&se of microcytic &nemi&, being compens&ted by the bone
m&rrow by norm&l sized cells but less of them) 4) microcytic/hypochrom&tic
&nemi&. Cells &re both sm&ller (microcytic) &nd without Hb (hypochromic)
– Clinic&l fe&tures: Anemi&, Koilonychi" (Spoon sh&ped n&ils), Pic" (will to
chew on things &bnorm&lly to try &nd get th&t d&mn iron!!).
– L&b findings include microcytic hypochromic RBC with &n incre"sed RDW
(RBC distribution width, me&suring if there is & v&rying sizes of RBC or &ll
s&me size), Low ferritin which me&ns TIBC up (liver m&king tr&nsferrin to
compens&te), Serum iron low, &nd % s&tur&tion low. Also FEP (free
erythrocyte protoporphyrin) is up since it c&nʼt bind the iron to join to Heme,
so it &ccumul&tes free. On blood sme&r weʼll &lso see th&t RBC &re sm&ller
th&n lymphocyte nuclei (should be +- s&me).
– Tre&tment would be Iron! (Ferrous sulf&te).
– Plummer-Vinson syndrome: iron deficiency &nemi& with esoph&ge&l web
(p&rti&l obstruction of esoph&gus) &nd &trophic glossitis. (Anemi&, dysph&gi&,
beefy-red tongue).

Anemi& of Chronic Dise&se

– Associ&ted with chronic infl&mm&tion or c&ncer, &ssoci&ted with hospit&lized
p&tients. Medi&ted by &cute ph&se re&ct&nts such &s Hepcidin, which locks
iron in stor&ge sites in m&croph&ges, which limits itʼs tr&nsfer from
m&croph&ges to erythroid precursors, which c&uses microcytic &nemi&. It &lso
suppresses EPO. An expl&n&tion is th&t b&cteri& requires iron for nutrition, so
the body rele&ses the hepcidin to derive the b&cteri& from thriving &nd the
hepcidin is &ctu&lly hurting us.
– L&b findings would be high ferritin (stor&ge), low TIBC (high tr&nsfer protein to
“try” &nd move it where itʼs needed), low serum iron &nd low % s&tur&tion (Hb
isnʼt &v&il&ble), &nd FEP is up (protoporphoryn is flo&ting free since it c&nʼt be
combined with heme to form Hb).
– S&me &s iron deficiency, first the p&tient will develop normocytic &nemi& &nd
then &lter microcytic.
– Tre&tment is to &ddress the c&use &nd EPO is useful in p&tients with c&ncer
for ex&mple.

Siderobl&stic &nemi&
– Defect in protoporphyrin synthesis, which le&ds in low heme, which results in
low Hb -> microcytic &nemi&.
 – &n import&nt enzyme is ALAS &nd vit&min B6 &s co-enzyme, th&tʼs &n e&rly
step.
– in & l&ter step, ferrochel&t&se is the enzyme th&t c&t&lyses the re&ction of
Protoporphyrin + iron -> heme, &nd h&ppens in mitochondri&.
– So in the erythroid precursor, while the protoporphyrin is being synthesized in
the mitochondri&, iron is tr&nsferred there to be &dded to the mitochondri& to
cre&te heme. If protoporphyrin is deficient, Iron will enter mitochondri" &nd
get tr&pped. Then it piles up there, &nd th&t cre&tes & ring of iron-lo&ded
mitochondri& &round the nucleus. “Iron l"den mitochondri"” or “ring
siderobl"sts”. (purssi&n blue st&in for iron m&rking)
– Siderobl&stic &nemi& c&n be congenit&l or &cquired, &nd the congenit&l one
commonly involves ALAS (r&te limiting enzyme in the e&rly re&ction). The
&cquired one occurs &s & result of "lcoholism, le"d poisoning &nd vit"min
B6 diet deficiency (Isoni&zid tre&tment for ex&mple c&uses this B6
deficiency).
– L&bor&tory findings would be high ferritin (lots of iron th&t c&nʼt &ctu&lly
cre&te heme), low TIBC (We h&ve much iron so no need for tr&nsfer), high
serum iron, &nd high iron s&tur&tion. Since iron c&n cre&te free r&dic&ls it kills
cells &nd le&ks out, m&croph&ges in bone m&rrow will digest it.

Th&l&ssemi&
– Decre&sed synthesis of globin ch&ins. Globin low which le&ds to low Hb,
resulting in microcytic &nemi&.
– Itʼs due to inherited mut&tion, &nd c&rriers &re protected &g&inst Pl&smodium
F&lcip&rum m&l&ri&.
– C&n be Alph& or Bet& th&l&ssemi&, b&sed on the &lph&/bet& ch&ins th&t &re
decre&sed. (3 norm&l Hb types &re HbF ("lph"2G&mm&2), HbA
(Alph"2Bet&2) &nd HbA2 (Alph"2Delt&2). So &lph& is most import&nt.
– Alph&-Th&l&ssemi&: usu&lly due to gene deletion, there &re norm&lly 4 "lph"
"lleles on chromosome 16. If 1 gene is deleted it is usu&lly &symptom&tic
since there &re 3 more &lleles &nd no worries. if 2 genes &re deleted, thereʼll
be & mild &nemi& with & slightly incre&sed RBC count, but itʼs import&nt if itʼs
& cis (2 on s&me chromosome) or tr&ns deletion (2 on opposite chromosome),
&nd cis is worse since thereʼs &n incre&sed risk of th&l&ssemi& in offspring
since th&t 1 chromosome m&y be inherited. More common in &si&ns. Tr&ns &re
more common in Afric&. If 3 genes &re deleted, thereʼs & severe &nemi&, but
no symptoms in fetus, &nd thereʼll be tetr&mers of B ch&ins since B2 c&nʼt join
with Alp&2, forming HbH which is p&thologic &nd d&m&ges RBCs &nd is seen
on electrophoresis. If 4 genes &re deleted the problem would express in the
fetus, leth&l in utero (hydrops fet&lis), thereʼll be tetr&mers of g&mm& ch&ins.
– Bet&-Th&l&ssemi&: due to gene mut&tions. there &re 2 bet& genes, on
chromosome 11. The mut&tion m&y results in &bsent production of bet& ch&in
(Bet&-null) or diminished production with is Bet&+. Mildest form of dise&se
 –

would be (B,B+), so one is good &nd the second one is diminished but
&symptom&tic with incre&sed RBC count. Microlytics, hypochromic RBCs &nd
t&rget RBC on sme&r. (A t&rget cell is like & bullseye cell, cre&ted when thereʼs
& reduced Hb in cytopl&sm with excess membr&ne &nd form this t&rget cell).
– Electrophoresis would show slightly decre&sed HbA &nd incre&sed HbA2 to
5% (norm&l 2.5%). Also incre&sed HbF to 2% (Norm&l 1%).
– (B-null/B-null) is the worst, presents with severe &nemi& & few months &fter
birth (since it does h&ve HbF which is ok since itʼs Alph&2G&mm&2. A
tetr&mers &ggreg&te &nd d&m&ge RBC c&using ineffective erythropoiesis &nd
extr&v&scul&r hemolysis since the spleen will recognize the &bnorm&lity &nd
destroy it. People with this problem will h&ve & m&ssive erythroid hyperpl&si&,
which c&uses exp&nsion of hem&topoeisis into m&rrow of skill &nd f&ci&l
bones. Also there might be extr&-medull&ry hem&topoiesis in liver &nd spleen
(Hep&tosplenomeg&ly), &lso thereʼs & risk of "pl"stic crisis with p&rvovirus
B19 which shuts down RBC production.
– Chronic tr"nsfusions &re often necess&ry, le&ds to risk for second&ry
hemochrom"tosis.
– On blood sme&r thereʼs microcytic, hypochromic t&rget cells with nucle&ted
RBC (if they &re m&de extr& medull&ry, some nucle&ted ones esc&pe to the
blood), on Electrophoresis there wonʼt be HbA, &nd thereʼll be incre&sed HbA2
&nd HbF.

M"crocytic Anemi"
– MCV > 100. Most commonly due to fol"te or vit"min B12 deficiency
(meg&lobl&stic &nemi&). Since less divisions occur &nd first dividing cells
rem&in (which &re quite l&rge), since DNA precursors &re &bsent.
– Vit&min B12 t&kes the methyl group from THF (form of fol&te which enters the
body), then B12 sends the methyl group to hemocysteine to form methionine.
Th&tʼs the only w&y THF c&n p&rticip&te in DNA synthesis.
– The term is Meg"lobl"stic "nemi" for Fol&te / B12 &nemi&.
– Hypersegmented neutrophils (more th&n 5 lobes, &lso kind of meg&lobl&stic)
&re &lso common, &nd meg&lobl&stic ch&nge in r&pidly-dividing epitheli&l
cells.
– Other c&uses of m&crocytic &nemi& &re Alcoholism, liver dise&se, &nd drugs
such &s 5-fu. (the &bove extr& ch&nges &re not present).
– Fol"te deficiency: obt&ined from veget&bles &nd fruits, &bsorbed in jejunum,
&nd the deficiency develops in months. So gener&lly poor diet is & c&use
(&lcoholics &nd elderly), incre&sed dem&nd (pregn&ncy, c&ncer, hemolytic
&nemi&), or when there is & us&ge of fol&te &nt&gonists such &s methotrex&te.
– Clinic&l findings &re m&crocytic RBCs &nd hypersegmented neutrophils,
glossitis, decre&sed serum fol&te, incre&sed serum hemocysteine (since it
doesnʼt get the methyl group from B12 to get to methionine). Methylm&lonic
&cid is norm&l th&t indic&tes B12 is OK.
 – B12 deficiency: R-binder t&kes the B12 &nd tr&vel through esoph&gus &nd
stom&ch till it re&ches sm&ll intestine, then it is cle&ved by p&ncre&s
prote&ses, &nd then B12 binds intrinsic f&ctor from p&riet&l cells in the
stom&ch, then itʼs &bsorbed in the ileum. Itʼs less common th&n Fol&te
deficiency &nd it t&kes ye&rs to develop due to l&rge hep&tic stores of vit&min
B12.
– Pernicious Anemi" is the most common c&use of B12 deficiency. There is &n
&utoimmune destruction of p&riet&l cells (body of stom&ch) which le&ds to IF
deficiency.
– Other c&uses of B12 deficiency &re P&ncre&tic insufficiency (enzymes cle&ves
B12 from R-binder), or d&m&ge to the termin&l ileum due to Crohn or b&cteri&
(c&nʼt be &bsorbed). Pure deficiency is r&re, except in strict veg&ns.
– clinic&lly, thereʼll be m&crocytic &nemi& with hypersegmented neutrophils,
glossitis, &nd sub&cute combined degener&tion of the spin&l cord
(methylm&lonic &cid c&nʼt be converted to S-CoA &nd then builds up in spin&l
cord myelin &nd c&uses itʼs degener&tion. (not seen in fol&te deficiency for
ex&mple).
– Low B12, high hemocysteine, high methylm"lonic "cid unlike fol&te
dificiency, symboling the B12 deficiency.

Normocytic Anemi"
– An &nemi& with norm&l CMV of 80-100. Due to incre&sed peripher&l
destruction or under-production. Reticulocyte counts help distinguish
between the etiologies.
– Reticulocytes &re young blood cells rele&sed from the bone m&rrow to m&ture.
On sme&r seen &s l&rger cells with bluish cytopl&sm (due to residu"l RNA).
norm&l count is 1-2% &nd RBC lifesp&n is 120 d&ys so every d&y 1-2% of RBC
&re removed &nd repl&ced by reticulocytes.
– If & bone m&rrow is functioning properly, it will respond to &nemi& by
incre&sing the RC to higher th&n 3%, however, Rc is hemocysteine in &nemi&.
Th&tʼs bec&use theyʼre me&sured &t & percent&ge of the RBC. It is corrected
by multiplying the count by Hct/45. Higher then 3% indic&tes good m&rrow
response, me&ns there is & peripher&l destruction. Less th&n 3% indic&tes
poor m&rrow response, underproduction.
– Peripher&l RBC destruction (Hemolysis): Divided into extr&v&scul&r (in the
org&ns such &s spleen) &nd intr&v&scul&r (in the vessels themselves). Both
result in &nemi& with good m&rrow response.
– Extr&v&scul&r hemolysis: Destruction by the reticuloendotheli&l system
(m&croph&ges of spleen, liver &nd lymph nodes). They consume the RBC &nd
bre&k down Hb. Globin is broken to &mino &cids, &nd the heme is broken to
iron (recycled) &nd protoporphyrin (goes to unconjug&ted bilirubin, which
goes bound to &lbumin, goes to liver for conjug&tion &nd go to bile).
– According to the &bove, the clinic&l &nd l&b findings would be &nemi&,
 –
splenomeg&ly, j&undice (unconjug&ted bilirubin), incre&sed risk for bilirubin
g&llstones, &nd m&rrow hyperpl&si& (bone m&rrow is fine &nd it is trying to
work) &nd reticulocyte count would be more th&n 3% (corrected).
– Intr&v&scul&r hemolysis: Hb p&ssed directly into the blood, which quickly
binds the h"ptoglobin &nd t&ke it to the spleen for the reprocessing. So &n
e&rly ch&nge is & decre&se of h&ptoglobin. Hb builds up in the blood, &nd
c&use hemoglobunuri&. And &lso thereʼll be hemosiderinuri& (in the tubules,
cells t&ke up the hemoglobin &nd turns it into hemociderin &nd l&ter f&ll off
into the urine).

Predomin&nt extr&v&scul&r hemolysis

– Heredit"ry spherocytosis: inherited defect to RBC cytoskeleton membr&ne
tethering proteins which c&uses p&rt of membr&ne to be lost. Most common
proteins involved &re spectrin, "nkyrin &nd b"nd 3.1. Membr&ne blebs &re
formed &nd lost over time, which c&uses the cell to be round inste&d of disc
(biconc&ve). There is & high RDW since some cells &re sm&ller &nd some
l&rger since the longer &n RBC lives the more membr&ne it loses.
– Those spherocytes &re less &ble to m&neuver through splenic sinusoids which
m&kes them be destroyed by splenic m&croph&ges &nd c&use &nemi&.
– In l&bor&tory weʼll see spherocytes, with loss of centr&l p&llor, higher RDW
&nd incre"sed MCHC (Since cytopl&sm rem&ins &bout the s&me while cells
shrink Hemoglobin is concentr&ted in the cell). Splenomeg"ly will &lso occur
(work hypertrophy), &long with j&undice (unconjug&ted bilirubin &nd bilirubin
g&llstones risk). There is &lso &n incre&sed risk for &pl&stic crisis with
p&rvovirus B19 infection of erythroid precursors.
– This is di&gnosed by osmotic fr&gility test (incre&sed fr&gility in hypotonic
solution). Splenectomy is the tre&tment since the &nemi& resolves, yet
Spherocytosis persist. Howell-Jolly bodies emerge in blood sme&r (RBC
which h&ve some p&rt of the nucleus left will not be removed by the spleen
since itʼll be &bsent &fter splenectomy).
– Sicle cell &nemi&: AR mut&tion in B ch&in of hemoglobin, norm&l glut&mic &cid
(hydrophilic) is repl&ced by v&line (hydrophobic). present in 10% of &fric&n
popul&tion, protects vs m&l&ri& f&lcip&rum.
– Arises when 2 &bnorm&l B genes &re present, &nd results in more th&n 90%
HbS in RBCs (since this is the one &ble to be produced). The problem with
HbS is th&t it polymerizes when it is deoxygen&ted. The polymers &ggreg&te
into needle-like structures resulting in sickle cells.
– Incre&sed risk of sickling would be with hypoxemi", dehydr"tion &nd
"cidosis.
– A protector f&ctor &g&inst sickling is HbF (High HbF &t birth is protective for
the first few months of life). So tre&tment with hydroxyure& is good since it
incre&ses levels of HbF.
– Cells continuously sickle &nd de-sickle while p&ssing through
 –
microcircul&tion, which results in complic&tions rel&ted to RBC membr&ne
d&m&ge over time. So with time they &re less flexible, c&using extr&v&scul&r
hemolysis (j&undice, unconjug&ted hyperbilirubinemi&, g&llstones..). Also
some of those cells will &lso lyse intr&v&scull&rily, so thereʼll be h&pto globin
(sc&venger molecule for free Hb in blood) &nd t&rget cells &re formed on
blood sme&r (cells dehydr&te &s the membr&ne gets d&m&ged, cytopl&sm
decre&ses like & b&sketb&ll &nd the t&rget cell is formed). Also there is &
m&ssive erythroid hyperpl&si& which results in exp&nsion of hem&topoiesis
into skull &nd f&ci&l bones &s well &s extr&medull&ry hem&topoiesis with
hep&tomeg&ly. There is &lso & risk of &pl&stic crisis with p&rvovirus B19
infection of erythroid precursors.
– Eventu&lly, irreversible sickling c&n develop, which le&ds to v&so-occlusion.
D"ctylitis is & common sign, which is swollen h&nds &nd feet due to v&so
occlusive inf&rcts of bones, commonly presenting in inf&nt.
– The v&so occlusive crisis in the spleen c&uses Autosplenectomy which le&ds
to shrunken fibrotic spleen. This c&uses incre&sed risk of infection with
enc&psul&ted org&nisms (H influenz&, strep pneumo..), Also S&lmonell&
p&r&typhi osteomyelitis. Howell-Jolly bodies on blood sme&r &re presents.
– If the v&so-occlusive crisis occurs in lung, we get &cute chest syndrome, with
chest p&in, shortness of bre&th, lung infiltr&tes.. precipit&ted by pneumoni&.
Most common c&use of de&th in &dults with the dise&se.
– V&so occlusive crisis c&n h&ppen to &ny other org&n such &s kidney &nd
more. &nd c&use relev&nt symptoms.
– Sickle cell tr&it: Itʼs “only” & tr&it when the p&tient one mut&ted B gene &nd
one norm&l. They produce both HbA &nd HbS, but the norm&l HbA will
&ctu&lly be & bit domin&nt which &ctu&lly doesnʼt c&use sickling! so
&symptom&tic with no &nemi&. The exception is ren&l medull& which through
extreme hypoxi" &nd hypertonicity, sickling is c&used. Results in micro
infr"ctions, le&ds to microscopic hem&turi& &nd eventu&lly decre"sed
"bility to concentr"te urine.
– L&b: Sickle cells &nd t&rget cells &re seen on blood sme&r in sickle cell
dise&se but not in tr&it. Met"bisulfite screen &llows to identify HbS, so will
be positive in both. Hb electrophoresis will &lso be useful since in dise&se for
ex&mple we wonʼt h&ve HbA &t &ll (since itʼs A2B2), in tr&it thereʼll be 55%
HbA.
– Hemoglobin C: Autosom&l recessive mut&tion in B ch&in of hemoglobin but
the norm&l glut&mic &cid is repl&ced by lysine, less common th&n sickle cell
dise&se, presents with mild &nemi& but wh&tʼs import&nt is HbC cryst"ls on
blood sme"r!

Predomin&nt intr&v&scul&r hemolysis

– PNH: P"roxysm"l nocturn"l hemoglobinuri": Activ&tion of complement &t
–
night (sh&llow bre&thing &nd high CO2 c&using respir&tory &cidosis) th&t
h&ppens sometimes &nd d&m&ges blood cells, c&using hemoglobinuri& in the
morning. The defect is "cquired &nd is resulting in &n &bsent GPI (&nchoring
protein expl&ined below). RBCS, WBCs &nd pl&telets &re &ll lysed.
– DAF &nd MIRL &re there on the RBC &nd other cells to prevent complement
from binding the RBCs &nd other cells &nd lysing them. They &re connected
by &n &nchor protein c&lled GPI which is &bsent in PNH.
– C&uses hemoglobinemi&, hemoglobinuri&, hemosiderinuri& (d&ys l&ter).
– Sucrose is & good test, when we &dd it to the serum, it &ctiv&ted complement
&nd we see if RBCs &re lysed, or &cidifying the serum. we c&n &lso look for
l&ck of CD55 (DAF) on RBC.
– M&in c&use of de&th is thrombosis of hep&tic, port&l or cerebr&l veins.
Destroyed pl&telets rele&se cytopl&smic contents into circul&tion inducing
thrombosis. A complic&tion is iron deficiency &nemi& (lost in hemoglobin in
urine). AML risk incre"sed.
– G6PD deficiency: X linked recessive of Gluth&tione deficiency since no G6PD
so no NADPH so no &bility to regener&te it &nd protect vs oxid&tive stress.
– Afric&n v&ri&nt is & mildly reduced h&lf life of it &nd mediterr&ne&n one with
m&rkedly reduced HL.
– It h&s protective role &g&ins m&l&ri& f&lcip&rum.
– c&uses of the relev&nt oxid&tive stress &re infection, drugs &nd f"v" be"ns.
Hb percipit&te &s Heinz body when the oxid&tive stress is introduced, which
is then removed by splenic m&croph&ges resulting in bite cells (splenic
m&croph&ge removes & piece of the cell) which is c&using intr&v&scul&r
hemolysis.
– Presents with hemoglobinuri& &nd b&ck p&in (nephrotoxic), occurs hours &fter
exposure.
– Heinz prep&r&tion is used to screen the dise&se. Enzyme studies confirm
deficiency.
– Immune hemolytic "nemi": IgG or IgM medi&ted destruction of RBCs. if itʼs
IgG medi&ted then it usu&lly involves extr&v&scul&r hemolysis. IgG binds RBC
in the rel&tively w&rm centr&l body, membr&ne of &ntibody-co&ted RBC is
gr&du&lly consumed by splenic m&croph&ges &nd results in spherocytosis.
Associ&ted with SLE, CLL &nd cert&in drugs.
– If itʼs IgM medi&ted, it usu&lly involves intr&v&scul&r hemolysis. It binds RBCs
&nd fixes complement in the rel&tively cold temper&ture of extremities (cold
&gglutinin). Associ&ted with Mycopl&sm& pneumoni&e &nd infectious
mononucleosis.
– Coombs test is used for di&gnosis. Direct tests if we h&ve RBCs which &re
"lre"dy bound by our IgG, by introducing &nti-IgG, which c&uses
&gglutin&tion if RBCs &re &lre&dy co&ted with IgG &ntibody. An indirect test
checks if the serum cont&ins "nti-self ABs in the serum. Anti IgG &nd test
RBC &re mixed with p&tientʼs serum. &gglutin&tion occurs if serum &ntibodies
 &re present.
– Micro"ngiop"thic hemolytic "nemi": Results from v&scul&r p&thology,
There is & cert&in thrombus in & sm&ll blood vessel, which c&uses the blood
cells coming to ch&nge their sh&pe when p&ssing, turning into schistocytes
(RBC which looks like & helmet). It occurs with microthrombi, prosthetic he&rt
v&lves (they cr&sh the RBC destroying them), &ortic stenosis (c&lcified v&lved
will &lso crush the RBC). M&l&ri& is &n infection of RBC &nd liver by &nopheles
mosquito.
– Fevers of m&l&ri&: F&lcip&rum: d&ily &nd not regul&r. Viv& &nd ov&le: fever
every 2 d&ys. M&l&ri&e: every d&y.

Anemi" due to under-production

– Decre&sed production of RBCs by bone m&rrow, ch&r&cterized by low
corrected RC (since m&rrow c&nnot compens&te). C&uses of microcytic &nd
m&crocytic &nemi&, ren&l f&ilure (less EPO), d&m&ge to bone m&rrow
precursor cells.
– P&rvovirus B19 infects progenitor red cells &nd stop erythropoiesis with pre-
existing m&rrow stress.
– Apl&stic &nemi&: D&m&ge to Hem&topoeitic stem cells, so p"ncytopeni".
induced by drugs &nd chemic&ls, vir&l infections &nd &utoimmune d&m&ge.
Cl&ssic finding is &n empty m&rrow, just f&t (&dipose) &nd no hem&topoietic
elements.

Myelophthisic process: p&thologic process th&t repl&ces bone m&rrow,

hem&topoiesis is imp&ired resulting in p&ncytopeni&.