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8/3/2019 6,Hemolytic Anemia
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1stintroduction1stintroduction
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Definition
Hemolytic anemias (HA) result
from a shortened erythrocytelife span ,increased or faster
destruction with insufficient
compensation from increasederythrocyte production.
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HA classification
according to etiological
factor
Intracorpuscular defects
Extracorpuscular defects
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Intracorpuscular defectsInheritedRBC
membrane defects(hereditary spherocytosis, HS)
enzyme defects ( glucose-6-phosphate dehydrogenase G-6-PD,
pyruvic ketolase, PK )hemoglobinopathies,
Sickle cell, thalassemias
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Acquired:PNH ( paroxysmal nocturnal hemoglobinuria )
PNH is caused by a defect in the formation
of protein anchor called GPI ( glycosylphosphatidyl inositol)Theloss of these cell-surface proteins enhancedsensitivity to complement-mediated cell
destruction. This destruction is intermittent(paroxysmal). The disease can affect peopleof any age.
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Extracorpuscular defectsInherited
Abetalipoproteinemia
A disorder of lipid metabolism inherited as an autosomal
recessive trait characterized by the near absence of
APOLIPOPROTEINS B and apoB-containing lipoproteins in
plasma. Microsomal triglyceride transfer protein is deficient or
absent in enterocytes. Clinical and laboratory findings includeacanthocytosis, hypocholesterolemia,
peripheral neuropathy, posterior column degeneration, ataxia,
and steatorrhea. Intellectual abilities may also be impaired.
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Acquired
autoimmune disease
Trauma and microangiopathic: HUS(hemolytic-uremic syndrome),
DIC,TTP
Infectious agents: protozoa, bacteriachemical damage: drugs, venoms
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HA classification
according to hematolysis occurred place
(1)Intravascular hemolysis
Lysis occurs within the circulation ,RBC membraneinjury (trauma, autoimmune, infection)
(2)Extravascular Hemolysis (most
common)Lysis occurs in the tissues (Splenic and hepatic
clearance of defective RBCs)
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causes of hemolysis :
immune reaction, chemistry,physics and biology factoreffect on RBC.such as
autoimmune HemolyticAnemia(AIHA
chemical intoxicant or medicine
after cardiac valve replacementinfection result in hemolysis anemia
hypersplenism
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.definite lab test for HAstep of diagnose HA :
First, must be sure whether HA exist
Then, analyze the reasonsThere are specific tests which identify the
specific types of hemolytic anemia. They areperformed after hemolysis has been established.
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display evidences of
hematoclasis increase
display evidences ofRBC
compensatory hyperplasia
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2nd
Screen tests ofhemolytic anemia
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Extravascular Hemolysis
Ingested by RE cell (spleen
& liver)
Intravascular Hemolysis
Hgb liberated in
blood vessel
Hgb + haptoglobin
Hgb + albumin
Hgb excreted
in urine
Heme Globin
Re-utilizedIron Protoporphyrin
Re-utilized bilirubin
q Serumhaptoglobin
+ hemalbumin
& plasma Hgb
+hemoglobinuria
& hemosidenuria
Hemolysis - RBC destruction
RE: reticulo-endothelium
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1.related test about RBC life shorten
and hematoclasis increase
(1) RBC life test: is the most direct evidence for
diagnosis. Direct measurement of the red cell lifespan by isotopic tagging techniques shows a
decreased life span.
Half life of health adult RBC : 25-35 days
Half life of HA:
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(2) RBC morphology change:
we can see spherocytosis ,sickle cell,
acanthocytosis , anisocytosis,polychromatic erythrocyte, stippling red
cell, Howell-Jollys Bodies, Cabots
ring Bodies, nucleated red cell
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(3) Elevated absolute reticulocyte
count
(4) Low red blood cell count and
hemoglobin
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(5) plasma lactic dehydrogenase
(PLDH) test:
RBC destroy LDH in cell release to
plasma elevated serum LDH .
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2.measurement of free-hemoglobin
in plasma
Referenc value: 1g/L), BG
incompatibility transfusion, PNH extravascular hemolysis is normal
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3.test of haptoglobin in serumReference value:0.7-1.5g/L
Clinical meaning:
decrease:intravasular hemolysis ( acute serious
IVH---0 ) , extravasular hemolysis and
liver disease increase :
infection, trauma, malignant tumor
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4.test of methemoglobin in plasma
Normal :
negative
Positive :
serious intravascular hemolysis
( Ferrihemoglobin )
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5.hematoglo
binuria test
Positive results: only occur in the
early days of acute IVH attack
6.Rous test (hemosiderinuria test)Positive results: chronic IVH and
lasting several weeks,such as PNH.In
the early stage of hemolysis, this testis temporarily negative.
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7.bilirubin metabolism abnormal
elevated unconjugated bilirubin
(UCB) in serum
jaundice
Increased urine and fecal
urobilinogen
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3rd
Tests ofMembrane defects
3rd
Tests ofMembrane defects
1. erythrocyte osmotic fragility test:
Red blood cell sensitivity to change inosmotic pressure. When exposed to ahypotonic concentration of sodium in a
solution, red cells take in more water, swelluntil the capacity of the cell membrane isexceeded, and burst
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reference range :
begin hemolysis: 0.42-0.46%4.2- 4.6g/L sodium chloride
complete hemolysis: 0.28-0.34%
4.2- 4.6g/L sodium chloride
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clinical meanings
to contrast with health adult above0.04g/LNaCL is (+)
Fragility increase:
Congenital spherocytosis ,
Immune hemolytic Anemia
Fragility decrease:thalassemia, IDA, cirrhosis
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2.Incubated osmotic fragility test:
3.autohemotysis and correction test
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4th
Tests ofEnzyme deficiencies
4th
Tests ofEnzyme deficiencies
Hemolytic anemia caused by rbc Enzyme
deficiencies also are called Erythrocyteenzymopathy. It refers to enzyme esp that
takes part in RBC metablism (mainly
glycometabolism ) have genetic deficiencies,
then result in changed activity, causehemolysis diseases.
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1. G6PDDeficiency
glucose-6-phosphate dehydrogenase Indications for testing
Acute or chronic non-spherocytic
Hemolytic Anemia Asymptomatic children with
significant risk factors (such asFavism )
Nonphysiologic Neonatal Jaundicewith risk factors
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Associated risk factors
(1). African, Mediterranean, orAsian ethnicity
(2). Family History of Jaundice,
Anemia or Splenomegaly
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2.methemoglobin reduction test
3.cyanide-Ascorbate test
4.nitro-tetrazolium test
5.pyruvate kinase ultravioletspectrometry
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5th
Test o
fhem
oglobinopathi
es
5th
Test o
fhem
oglobinopathi
es
hemoglolin electrophoresis
reference value :
adults hemoglolin include HbA
(E2 F2 ),HbA
2(E2 H2 ), and HbF(E2 K2)A 96-98% A2 1-3%F 1%
Clinical significance:
HbA2 increase: mitis -Mediterraneananemiasome megaloblastic anemia
HbA2 decrease :IDA, sideroblastic anemia
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6th
Test ofauto immune hemolyticanemia (AIAH)
6th
Test ofauto immune hemolyticanemia (AIAH)
Antihuman globulin test (Coombs Test )
The Direct Coombs Test
The Indirect Coombs Test
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The Direct Coombs Test
Looks for immunoglobulin &/or complement of
surface of red blood cell (normally neither found
on RBC surface)
Coombs reagent - combination of anti-humanimmunoglobulin & anti-human complement
Mixed with patients red cells; if immunoglobulin
or complement are on surface, Coombs reagent
will link cells together and cause agglutination of
RBCs
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The DirectC
oombs Test
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The Indirect Coombs Test
Looks for anti-red blood cell antibodies inthe patients serum, using a panel of redcells with RH positive O type (have no
antigen in RBC surface )Combine patients serum with cells from a
panel ofRBCs with known antigens
Add
Coombs
reagent to this mixture
If anti-RBC antibodies (low-order antibody )are in serum, agglutination occurs
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Normal :Negative
Positive :
Hemolytic Disease of the Newborn (RhSensitization)
Auto immune Hemolytic Anemia
Paroxysmal Cold
Hemoglobinuria
Transfusion reaction
Medications
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7th
Test of paroxysmalnocturnal hemoglobinuria
(PHN )
7th
Test of paroxysmalnocturnal hemoglobinuria
(PHN )
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1. acid serum hemolysis test
(Ham test) :Principle: RBC of PNH patient is sensitive
with complement , in acidifying health serum
pH 6.6~6.8 ),after incubating in 370C,RBCmay occur hemolysis.
Reference value : (-)
always PHN is positive ,this test can finallydiagnosis PNH.
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2.sucrose lysis test
The ion concentration of sucrose solution
is low , after incubating, the combinationof complement and RBC membrane can
be strengthened. PNH patient RBC
surface form pinhole sucrose will go into
RBC, hemolysis then happens.
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normalNegative
clincial meaning
positive can be seen in PNH
hereditary spherocytosis ( HS )
autoimmune hemolytic anemia.
This test can be PNH`s screen test
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Good Luck!!!!Good Luck!!!!