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AnemiasAnemiasDr. Claudia CladovanDr. Claudia Cladovan

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APPROACH TO THE CHILDAPPROACH TO THE CHILD

WITH ANEMIAWITH ANEMIA Finding the cause is always important evenFinding the cause is always important even

though anemia in childhood has manythough anemia in childhood has manycausescauses

The cause is suggested by a careful history The cause is suggested by a careful history Nutritional causes should be addressed byNutritional causes should be addressed by

inquiry aboutinquiry about– dietary intae!dietary intae!

– growth and development!growth and development!– symptoms of chronic disease!symptoms of chronic disease!

– malabsorption!malabsorption!

– or blood lossor blood loss

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WITH ANEMIAWITH ANEMIA "emolytic disease may be suggested by"emolytic disease may be suggested by

– a history of #aundice $including neonatal #aundice%a history of #aundice $including neonatal #aundice%

– or by a family history of anemia! #aundice! gallbladderor by a family history of anemia! #aundice! gallbladderdisease! splenomegaly! or splenectomydisease! splenomegaly! or splenectomy

The child&s ethnic bacground may suggest the The child&s ethnic bacground may suggest thepossibility ofpossibility of– certain hemoglobinopathiescertain hemoglobinopathies

– or of de'ciencies of red cell en(ymes such as glucose)*)or of de'ciencies of red cell en(ymes such as glucose)*)phosphate dehydrogenase $+*,D%phosphate dehydrogenase $+*,D%

The age of the patient is important The age of the patient is important– iron de'ciency anemia and beta)globin disorders presentiron de'ciency anemia and beta)globin disorders present

more commonly between * and - months of agemore commonly between * and - months of age

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WITH ANEMIAWITH ANEMIA The physical e/amination may also reveal clues to The physical e/amination may also reveal clues to

the cause of anemia.the cause of anemia.– ,oor growth may suggest chronic disease or,oor growth may suggest chronic disease or

hypothyroidism.hypothyroidism.

–Congenital anomalies may be associated with constitutionalCongenital anomalies may be associated with constitutionalaplastic anemia $Fanconi&s anemia% or with constitutionalaplastic anemia $Fanconi&s anemia% or with constitutionalhypoplastic anemia $Diamond)0lacfan anemia%.hypoplastic anemia $Diamond)0lacfan anemia%.

– 1ther disorders may be suggested by the 'ndings of1ther disorders may be suggested by the 'ndings of petechiae or purpura $leuemia! aplastic anemia! hemolyticpetechiae or purpura $leuemia! aplastic anemia! hemolytic

uremic syndrome%!uremic syndrome%!

#aundice $hemolysis or liver disease%! #aundice $hemolysis or liver disease%!

generali(ed lymphadenopathy $leuemia! #uvenile rheumatoidgenerali(ed lymphadenopathy $leuemia! #uvenile rheumatoidarthritis! "23 infection%!arthritis! "23 infection%!

splenomegaly $leuemia! sicle syndromes! hereditarysplenomegaly $leuemia! sicle syndromes! hereditaryspherocytosis! liver disease! hypersplenism%!spherocytosis! liver disease! hypersplenism%!

or evidence of chronic or recurrent infections.or evidence of chronic or recurrent infections.

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WITH ANEMIAWITH ANEMIA The initial laboratory evaluation of the anemic The initial laboratory evaluation of the anemic

child generally consists ofchild generally consists of

– a complete blood count $C0C% with di4erential anda complete blood count $C0C% with di4erential and

platelet count!platelet count!

– review of the peripheral blood smear!review of the peripheral blood smear!

– and usually a reticulocyte count.and usually a reticulocyte count.

The diagnostic scheme depends principally on The diagnostic scheme depends principally on

the 5C3 to determine whether the anemia isthe 5C3 to determine whether the anemia is– microcytic!microcytic!

– normocytic!normocytic!

– or macrocytic.or macrocytic.

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WITH ANEMIAWITH ANEMIA

5icrocytic anemias5icrocytic anemias

– iron de'ciency is an important cause ofiron de'ciency is an important cause of

microcytic anemia! especially between *microcytic anemia! especially between *

and - months of ageand - months of age

– a trial of therapeutic iron is appropriatea trial of therapeutic iron is appropriate

in such childrenin such children

– if a trial of therapeutic iron fails toif a trial of therapeutic iron fails tocorrect the anemia and microcytosis)correct the anemia and microcytosis)

then further laboratory evaluation isthen further laboratory evaluation is

required.required.

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WITH ANEMIAWITH ANEMIA 6eticulocyte count and the peripheral blood smear6eticulocyte count and the peripheral blood smear

– determine whether a normocytic or macrocytic anemia isdetermine whether a normocytic or macrocytic anemia isdue to hemolysis.due to hemolysis.

– hemolytic disease is associated with an elevatedhemolytic disease is associated with an elevated

reticulocyte countreticulocyte count– review of the peripheral smear for evidence of hemolysisreview of the peripheral smear for evidence of hemolysis$eg! spherocytes! red cell fragmentation! sicle forms% is$eg! spherocytes! red cell fragmentation! sicle forms% isimportant in the evaluation of children with normocyticimportant in the evaluation of children with normocyticanemias and low reticulocyte countsanemias and low reticulocyte counts

Autoimmune hemolysis can be e/cluded byAutoimmune hemolysis can be e/cluded byCoombs& testingCoombs& testing

6eview of blood counts and the peripheral smears6eview of blood counts and the peripheral smearsof the mother and father may suggest congenitalof the mother and father may suggest congenitaldisorders such as hereditary spherocytosisdisorders such as hereditary spherocytosis

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WITH ANEMIAWITH ANEMIA Children with normocytic or macrocytic anemias!Children with normocytic or macrocytic anemias!

with relatively low reticulocyte counts and nowith relatively low reticulocyte counts and noevidence of hemolysis on the blood smear! usuallyevidence of hemolysis on the blood smear! usuallyhave anemias caused by inadequate erythropoiesishave anemias caused by inadequate erythropoiesisin the bone marrow.in the bone marrow.– presence of neutropenia or thrombocytopenia in suchpresence of neutropenia or thrombocytopenia in such

children suggests bone marrow failure and the possibilitychildren suggests bone marrow failure and the possibilityof aplastic anemia or malignancyof aplastic anemia or malignancy

– usually dictates e/amination of the bone marrowusually dictates e/amination of the bone marrow

,ure red cell aplasia may be,ure red cell aplasia may be

– constitutional $Diamond)0lacfan anemia%!constitutional $Diamond)0lacfan anemia%!– acquired and transient $transient erythroblastopenia ofacquired and transient $transient erythroblastopenia ofchildhood%!childhood%!

– a manifestation of a systemic disease such as renala manifestation of a systemic disease such as renaldisease or hypothyroidism!disease or hypothyroidism!

– or due to malnutrition or de'ciencies of folate oror due to malnutrition or de'ciencies of folate or

cobalamincobalamin

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PURE RED CELL APLASIAPURE RED CELL APLASIA

CONGENITAL HYPOPLASTIC ANEMIACONGENITAL HYPOPLASTIC ANEMIA

(Diamond-Blackan An!mia" (Diamond-Blackan An!mia" G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$

– 6are cause of anemia presents in6are cause of anemia presents in

infancy or early childhood.infancy or early childhood.

– The cause of the disorder is unclear! and The cause of the disorder is unclear! and

both autosomal dominant andboth autosomal dominant and

autosomal recessive modes ofautosomal recessive modes of

inheritance have been suggested.inheritance have been suggested.

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(Diamond-Blackan An!mia" (Diamond-Blackan An!mia" Clinical &indin'$Clinical &indin'$

A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+

– chronic anemia! such as pallor! andchronic anemia! such as pallor! andcongestive heart failurecongestive heart failure

– short stature or other congenitalshort stature or other congenital

anomalies are present in 789 patients.anomalies are present in 789 patients.

variety of anomalies have been described!variety of anomalies have been described!and those a4ecting the head! face! andand those a4ecting the head! face! and

thumbs are probably the most common.thumbs are probably the most common.

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(Diamond-Blackan An!mia" (Diamond-Blackan An!mia" T#!a%m!n%T#!a%m!n%

– 1ral corticosteroids should be initiated as soon as1ral corticosteroids should be initiated as soon asthe diagnosis of Diamond)0lacfan anemia is madethe diagnosis of Diamond)0lacfan anemia is made prednisone! - mg8g8d!prednisone! - mg8g8d!

– Chronic red cell transfusion therapy inevitablyChronic red cell transfusion therapy inevitablycauses hemosiderosis and the need for chelationcauses hemosiderosis and the need for chelationwith parenteral defero/amine.with parenteral defero/amine.

– 0one marrow transplantation is an alternative0one marrow transplantation is an alternativetherapytherapy

– "ematopoietic growth factors have been used in"ematopoietic growth factors have been used insome cases with limited success.some cases with limited success.

:npredictable! spontaneous remissions:npredictable! spontaneous remissionsoccasionally occur.occasionally occur.

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NUTRITIONAL ANEMIASNUTRITIONAL ANEMIAS

IRON DE&ICIENCY ANEMIAIRON DE&ICIENCY ANEMIA G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$ Normal term infants are born with su;cient iron stores toNormal term infants are born with su;cient iron stores to

prevent iron de'ciency for the 'rst months of life.prevent iron de'ciency for the 'rst months of life. Thereafter! enough iron needs to be absorbed to eep pace Thereafter! enough iron needs to be absorbed to eep pace

with the needs of rapid growth.with the needs of rapid growth.

For this reason! nutritional iron de'ciency is most commonFor this reason! nutritional iron de'ciency is most commonbetween * and - months of life.between * and - months of life.

A de'ciency earlier than * months of age may occur if ironA de'ciency earlier than * months of age may occur if ironstores at birth are reduced bystores at birth are reduced by– prematurity!prematurity!– small birth weight!small birth weight!

– neonatal anemia!neonatal anemia!– or perinatal blood loss or if there is subsequent iron loss due toor perinatal blood loss or if there is subsequent iron loss due to

hemorrhage.hemorrhage. 2ron)de'cient children older than - months of age should be2ron)de'cient children older than - months of age should be

investigated for blood loss.investigated for blood loss.

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IRON DE&ICIENCY ANEMIAIRON DE&ICIENCY ANEMIA

Clinical &indin'$Clinical &indin'$

A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+ – 5ild iron de'ciency is usually asymptomatic.5ild iron de'ciency is usually asymptomatic.

– 2n infants with more severe iron de'ciency!2n infants with more severe iron de'ciency!

pallor! fatigue! irritability! and delayed motorpallor! fatigue! irritability! and delayed motor

development are common.development are common.

– Children whose iron de'ciency is due in partChildren whose iron de'ciency is due in partto ingestion of unforti'ed cow&s mil may beto ingestion of unforti'ed cow&s mil may be

fat and

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IRON DE&ICIENCY ANEMIAIRON DE&ICIENCY ANEMIA Clinical &indin'$Clinical &indin'$ 0. =aboratory Findings>0. =aboratory Findings>

– The severity of anemia depends on the degree of iron The severity of anemia depends on the degree of ironde'ciency! and the hemoglobin may be as low as 9) g8d= inde'ciency! and the hemoglobin may be as low as 9) g8d= in

severe cases.severe cases.– 6ed cells are microcytic and hypochromic with a low 5C3 and6ed cells are microcytic and hypochromic with a low 5C3 andlow 5C".low 5C".

– The reticulocyte count is usually normal but may be slightly The reticulocyte count is usually normal but may be slightlyelevated in severe cases.elevated in severe cases.

– 2ron studies show2ron studies show a decreased serum ferritina decreased serum ferritin low serum iron!low serum iron!

elevated total iron)binding capacity!elevated total iron)binding capacity!

and decreased transferrin saturation.and decreased transferrin saturation.

free erythrocyte protoporphyrin is elevated.free erythrocyte protoporphyrin is elevated.

– The bone marrow e/amination is not helpful in the diagnosis The bone marrow e/amination is not helpful in the diagnosis

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IRON DE&ICIENCY ANEMIAIRON DE&ICIENCY ANEMIA T#!a%m!n%T#!a%m!n%

– oral dose of elemental iron is )* mg8g8d in threeoral dose of elemental iron is )* mg8g8d in threedivided daily doses.divided daily doses.

– mild cases may be treated with 9 mg8g8d given oncemild cases may be treated with 9 mg8g8d given once

daily before breafast.daily before breafast.– parenteral administration of iron is rarely necessary.parenteral administration of iron is rarely necessary.– 2ron therapy results in2ron therapy results in

an increased reticulocyte count within 9)? days! which isan increased reticulocyte count within 9)? days! which isma/imal between ? and @ days.ma/imal between ? and @ days.

hemoglobin level begins to increase thereafter.hemoglobin level begins to increase thereafter.

moderate to severe cases! an elevated reticulocyte count 7moderate to severe cases! an elevated reticulocyte count 7wee after initiation of therapy con'rms the diagnosiswee after initiation of therapy con'rms the diagnosis

iron de'ciency is the only cause of anemia! adequateiron de'ciency is the only cause of anemia! adequatetreatment usually results in a resolution of the anemia withintreatment usually results in a resolution of the anemia within)* wees.)* wees.

Treatment is generally continued for a few additional months Treatment is generally continued for a few additional months

to replenish iron stores.to replenish iron stores.

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NUTRITIONAL ANEMIASNUTRITIONAL ANEMIAS MEGALOBLASTIC ANEMIASMEGALOBLASTIC ANEMIAS

G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$ 5egaloblastic anemia is a macrocytic anemia caused5egaloblastic anemia is a macrocytic anemia caused

by de'ciency of cobalamin $vitamin 07-%! folic acid! orby de'ciency of cobalamin $vitamin 07-%! folic acid! orboth.both.

Cobalamin de'ciency due to dietary insu;ciency mayCobalamin de'ciency due to dietary insu;ciency mayoccur inoccur in– infants whoinfants who are breast)fed by mothers who are strictare breast)fed by mothers who are strict

vegetarians or who have pernicious anemia.vegetarians or who have pernicious anemia.

– intestinal malabsorption occurs with Crohn&s disease! chronicintestinal malabsorption occurs with Crohn&s disease! chronicpancreatitis! bacterial overgrowth of the small bowel! or afterpancreatitis! bacterial overgrowth of the small bowel! or after

surgical resection of the terminal ileum.surgical resection of the terminal ileum.– de'ciencies due to inborn errors of metabolismde'ciencies due to inborn errors of metabolism

$transcobalamin 22 de'ciency! methylmalonic aciduria% have$transcobalamin 22 de'ciency! methylmalonic aciduria% havealso been described.also been described.

– malabsorption of cobalamin due to de'ciency of intrinsicmalabsorption of cobalamin due to de'ciency of intrinsicfactor $pernicious anemia% is rare in childhood.factor $pernicious anemia% is rare in childhood.

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Clinical &indin'$Clinical &indin'$

A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+ – 2nfants with megaloblastic anemia may show pallor2nfants with megaloblastic anemia may show pallor

and mild #aundice due to ine4ective erythropoiesis.and mild #aundice due to ine4ective erythropoiesis.– Classically! the tongue is smooth and beefy red.Classically! the tongue is smooth and beefy red.

– 2nfants with cobalamin de'ciency may be irritable2nfants with cobalamin de'ciency may be irritable

and may be poor feeders.and may be poor feeders.

– 1lder children with cobalamin de'ciency may1lder children with cobalamin de'ciency may

complain of paresthesias! weaness! or ancomplain of paresthesias! weaness! or an

unsteady gait and may show decreased vibratoryunsteady gait and may show decreased vibratory

sensation and proprioception on neurologicsensation and proprioception on neurologic

e/amination.e/amination.

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Clinical &indin'$Clinical &indin'$ 0. =aboratory Findings>0. =aboratory Findings>

– an elevated 5C3 and mean corpuscular hemoglobin $5C"%.an elevated 5C3 and mean corpuscular hemoglobin $5C"%.– blood smear shows numerous macro)ovalocytes with anisocytosisblood smear shows numerous macro)ovalocytes with anisocytosis

and poiilocytosis.and poiilocytosis.– Neutrophils are large and have hypersegmented nuclei.Neutrophils are large and have hypersegmented nuclei.– The white cell count and the platelet count are normal with mild The white cell count and the platelet count are normal with mild

de'ciencies! but may be decreased in more severe cases.de'ciencies! but may be decreased in more severe cases.– /amination of the bone marrow typically shows erythroid/amination of the bone marrow typically shows erythroid

hyperplasia with large erythroid and myeloid precursors.hyperplasia with large erythroid and myeloid precursors. There is nuclear)cytoplasmic dissociation and ine4ective erythropoiesis. There is nuclear)cytoplasmic dissociation and ine4ective erythropoiesis.

– The serum indirect bilirubin concentration may be slightly elevated. The serum indirect bilirubin concentration may be slightly elevated.

– Children with cobalamin de'ciency have a low serum vitamin 07-Children with cobalamin de'ciency have a low serum vitamin 07-level.level.– 2n addition! the urinary concentration of methylmalonic acid is2n addition! the urinary concentration of methylmalonic acid is

signi'cantly elevated.signi'cantly elevated.– Assessment of folate stores is best done by measuring the level ofAssessment of folate stores is best done by measuring the level of

red cell folatered cell folate

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T#!a%m!n%T#!a%m!n% Treatment of cobalamin de'ciency due to Treatment of cobalamin de'ciency due to

inadequate dietary intaeinadequate dietary intae– 2s readily accomplished with oral supplementation.2s readily accomplished with oral supplementation.

– 5ost cases! however! are due to intestinal malabsorption5ost cases! however! are due to intestinal malabsorptionand require parenteral treatment.and require parenteral treatment.

– 2n severe cases! parenteral therapy may induce life)2n severe cases! parenteral therapy may induce life)threatening hypoalemia and require supplementalthreatening hypoalemia and require supplementalpotassium.potassium.

Folic acid de'ciencyFolic acid de'ciency– 2s e4ectively treated with oral folic acid in most cases.2s e4ectively treated with oral folic acid in most cases.– Children at ris for the development of folic acidChildren at ris for the development of folic acid

de'ciencies such as premature infants and those withde'ciencies such as premature infants and those withchronic hemolysis are usually given supplementary folicchronic hemolysis are usually given supplementary folicacid prophylacticallyacid prophylactically

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CONGENITAL HEMOLYTIC ANEMIAS+CONGENITAL HEMOLYTIC ANEMIAS+

RED CELL MEMBRANE DE&ECTSRED CELL MEMBRANE DE&ECTS

+eneral considerations+eneral considerations

The congenital hemolytic anemias are The congenital hemolytic anemias are

usually divided into three categories>usually divided into three categories>

– defects of the red cell membrane!defects of the red cell membrane!

– hemoglobinopathies!hemoglobinopathies!

– and disorders of red cell metabolism.and disorders of red cell metabolism.

"ereditary spherocytosis and"ereditary spherocytosis and

elliptocytosis are the most commonelliptocytosis are the most common

red cell membrane disordersred cell membrane disorders

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HEREDITARY SPHEROCYTOSISHEREDITARY SPHEROCYTOSIS G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$ 2s a relatively common inherited hemolytic anemia2s a relatively common inherited hemolytic anemia The hallmar of hereditary spherocytosis is the The hallmar of hereditary spherocytosis is the

presence of microspherocytes in the peripheralpresence of microspherocytes in the peripheralblood.blood.

The disease is inherited in an autosomal dominant The disease is inherited in an autosomal dominantfashion in about B of casesE the remainder arefashion in about B of casesE the remainder arethought to be autosomal recessive or to be causedthought to be autosomal recessive or to be caused

by new mutations.by new mutations. "ereditary spherocytosis is the result of a partial"ereditary spherocytosis is the result of a partial

de'ciency of spectrin. an important structuralde'ciency of spectrin. an important structuralprotein of the red cell membrane seletonprotein of the red cell membrane seleton

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HEREDITARY SPHEROCYTOSISHEREDITARY SPHEROCYTOSIS Clinical &indin'$Clinical &indin'$ A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+

– ymptoms and signs of hereditary spherocytosis areymptoms and signs of hereditary spherocytosis arethose related to hemolytic anemia.those related to hemolytic anemia.

– igni'cant hyperbilirubinemia in the newborn period.igni'cant hyperbilirubinemia in the newborn period.– plenomegaly subsequently develops in the ma#orityplenomegaly subsequently develops in the ma#ority

and is usually present by the age of ? years.and is usually present by the age of ? years.– Gaundice is variably present and in many patients may Gaundice is variably present and in many patients may

only be noted during infection.only be noted during infection.

– ,atients with signi'cant chronic anemia may complain of,atients with signi'cant chronic anemia may complain ofpallor! fatigue! or malaise.pallor! fatigue! or malaise.– 2ntermittent e/acerbations of the anemia are caused by2ntermittent e/acerbations of the anemia are caused by

increased hemolysis or by aplastic crises and may beincreased hemolysis or by aplastic crises and may beassociated with severe weaness! fatigue! fever!associated with severe weaness! fatigue! fever!abdominal pain! or even congestive heart failure.abdominal pain! or even congestive heart failure.

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HEREDITARY SPHEROCYTOSISHEREDITARY SPHEROCYTOSIS Clinical &indin'$Clinical &indin'$ A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+

– Com*lica%ion$Com*lica%ion$ evere #aundice may occur in the neonatalevere #aundice may occur in the neonatal

period and! if not controlled by phototherapy!period and! if not controlled by phototherapy!may occasionally require e/change transfusion.may occasionally require e/change transfusion.

plenectomy is. associated with an increasedplenectomy is. associated with an increased

ris of overwhelming bacterial infections!ris of overwhelming bacterial infections!particularly with pneumococci.particularly with pneumococci.

+allstones occur in *)@ of adults who have+allstones occur in *)@ of adults who havenot undergone splenectomy and may form asnot undergone splenectomy and may form asearly as B)7 years of age.early as B)7 years of age.

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HEREDITARY SPHEROCYTOSISHEREDITARY SPHEROCYTOSIS Clinical &indin'$Clinical &indin'$ 0. =aboratory Findings>0. =aboratory Findings>

– 5ost patients have mild chronic hemolysis with hemoglobin values5ost patients have mild chronic hemolysis with hemoglobin valuesbetween H and 7- g8d=.between H and 7- g8d=.

– 2n some cases! the hemolysis is fully compensated and the2n some cases! the hemolysis is fully compensated and the

hemoglobin is in the normal range.hemoglobin is in the normal range.– 6are cases of severe disease require frequent transfusions.6are cases of severe disease require frequent transfusions.– The anemia is usually normocytic and hyperchromic! and many The anemia is usually normocytic and hyperchromic! and many

patients have an elevated 5C"C.patients have an elevated 5C"C.– The blood smear shows numerous microspherocytes and The blood smear shows numerous microspherocytes and

polychromasia.polychromasia.– The reticulocyte count is elevated and is often higher than might The reticulocyte count is elevated and is often higher than might

be e/pected for the degree of anemia.be e/pected for the degree of anemia.– Ihite blood cells and platelets are usually normal.Ihite blood cells and platelets are usually normal.– The osmotic fragility is increased! particularly after incubation at The osmotic fragility is increased! particularly after incubation at

9@JC for - hours.9@JC for - hours.– erum bilirubin usually shows an elevation in the uncon#ugatederum bilirubin usually shows an elevation in the uncon#ugated

fraction.fraction.

– Coombs& testing is negative.Coombs& testing is negative.

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HEREDITARY SPHEROCYTOSISHEREDITARY SPHEROCYTOSIS T#!a%m!n%T#!a%m!n% upportive measures include the administration ofupportive measures include the administration of

folic acid to prevent the development of red cellfolic acid to prevent the development of red cell

hypoplasia due to folate de'ciency.hypoplasia due to folate de'ciency. Acute e/acerbations of anemia due to increasedAcute e/acerbations of anemia due to increased

rates of hemolysis or to aplastic crises due torates of hemolysis or to aplastic crises due toinfection with human parvovirus may be severeinfection with human parvovirus may be severeenough to require red cell transfusions.enough to require red cell transfusions.

plenectomy is performed in many cases andplenectomy is performed in many cases andalways results in signi'cant improvement.always results in signi'cant improvement.

All patients scheduled for splenectomy should beAll patients scheduled for splenectomy should beimmuni(ed with pneumococcal vaccine prior toimmuni(ed with pneumococcal vaccine prior to

the procedurethe procedure

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HEMOGLOBINOPATHBESHEMOGLOBINOPATHBES

+eneral considerations+eneral considerations The hemoglobinopathies are generally classi'ed The hemoglobinopathies are generally classi'ed

into two ma#or groups.into two ma#or groups. The 'rst! the thalassemias! are caused by The 'rst! the thalassemias! are caused by

quantitative de'ciencies in the production ofquantitative de'ciencies in the production ofglobin chains.globin chains.– These quantitative defects in globin synthesis result in a These quantitative defects in globin synthesis result in a

microcytic and hypochromic anemia.microcytic and hypochromic anemia.

The second group of hemoglobinopathies are The second group of hemoglobinopathies arethose caused by structural abnormalities of globinthose caused by structural abnormalities of globinchains.chains.– The most important of these! hemoglobins ! C! and ! The most important of these! hemoglobins ! C! and !

are all the result of point mutations and single aminoare all the result of point mutations and single aminoacid substitutions in the globin.acid substitutions in the globin.

CONGENITAL HEMOLYTIC ANEMIAS

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ALPHA-THALASSEMIAALPHA-THALASSEMIA

G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$

5ost of the K)thalassemia syndromes5ost of the K)thalassemia syndromes

are the result of deletions of one or moreare the result of deletions of one or more

of the alpha)globin genes onof the alpha)globin genes on

chromosome 7*.chromosome 7*.

Normal diploid cells have four alpha)Normal diploid cells have four alpha)

globin genes! and thus the variableglobin genes! and thus the variableseverity of the alpha)thalassemiaseverity of the alpha)thalassemia

syndromes is related to the number ofsyndromes is related to the number of

gene deletions.gene deletions.

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CONGENITAL HEMOLYTIC ANEMIASCONGENITAL HEMOLYTIC ANEMIAS

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Clinical &indin'$Clinical &indin'$ ,ersons with one alpha)globin gene $three)gene,ersons with one alpha)globin gene $three)gene

deletion%deletion%– have a moderately severe microcytic hemolytic anemia $"b @)have a moderately severe microcytic hemolytic anemia $"b @)

7 g8d=%!7 g8d=%!– often accompanied by hepatosplenomegaly and some bonyoften accompanied by hepatosplenomegaly and some bony

abnormalities caused by the e/panded medullary space.abnormalities caused by the e/panded medullary space.– reticulocyte count is elevated!reticulocyte count is elevated!– and the red cells show mared hypochromia and microcytosisand the red cells show mared hypochromia and microcytosis

with signi'cant poiilocytosis and some basophilic stippling.with signi'cant poiilocytosis and some basophilic stippling.– "emoglobin electrophoresis in the neonatal period typically"emoglobin electrophoresis in the neonatal period typically

shows 7?)-? 0art hemoglobin.shows 7?)-? 0art hemoglobin.– =ater in life! hemoglobin " $composed of four alpha)globin=ater in life! hemoglobin " $composed of four alpha)globin

chains% is detected and may mae up as much as -)9 of thechains% is detected and may mae up as much as -)9 of thehemoglobin.hemoglobin.

– 2ncubation of red cells with brilliant cresyl blue $hemoglobin "2ncubation of red cells with brilliant cresyl blue $hemoglobin "preparation% shows inclusion bodies formed by denaturedpreparation% shows inclusion bodies formed by denatured

hemoglobin ".hemoglobin ".


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Clinical &indin'$Clinical &indin'$ The deletion of all four alpha)globin genes The deletion of all four alpha)globin genes

– causes severe intrauterine anemia and asphy/iacauses severe intrauterine anemia and asphy/ia

– results in hydrops fetalis and fetal demise orresults in hydrops fetalis and fetal demise orneonatal death shortly following delivery.neonatal death shortly following delivery.

– There is e/treme pallor and massive There is e/treme pallor and massivehepatosplenomegaly.hepatosplenomegaly.

– "emoglobin electrophoresis reveals a"emoglobin electrophoresis reveals apredominance of 0arts hemoglobin with apredominance of 0arts hemoglobin with acomplete absence of normal fetal or adultcomplete absence of normal fetal or adulthemoglobin.hemoglobin.


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T#!a%m!n%T#!a%m!n% Asymptomatic persons require no treatment.Asymptomatic persons require no treatment. Those with hemoglobin " disease should receive Those with hemoglobin " disease should receive

supplemental folic acid and avoid the o/idant drugssupplemental folic acid and avoid the o/idant drugs

that cause hemolysis.that cause hemolysis. The anemia may also be e/acerbated during periods The anemia may also be e/acerbated during periods

of infection! and transfusions may be required.of infection! and transfusions may be required. 1ccasionally! infants with hemoglobin " disease may1ccasionally! infants with hemoglobin " disease may

show failure)to)thrive without red cell transfusions.show failure)to)thrive without red cell transfusions.

"ypersplenism may develop later in childhood and"ypersplenism may develop later in childhood andrequire surgical splenectomy.require surgical splenectomy.

+enetic counseling and prenatal diagnosis should be+enetic counseling and prenatal diagnosis should beo4ered to families at ris for children with hemoglobino4ered to families at ris for children with hemoglobin" disease or fetal hydrops." disease or fetal hydrops.


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BETA-THALASSEMIABETA-THALASSEMIA G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$ 2n contrast to the four alpha)globin genes! only two beta)2n contrast to the four alpha)globin genes! only two beta)

glohin genes are present in diploid cells! one on eachglohin genes are present in diploid cells! one on eachchromosome 77.chromosome 77.

ome beta )thalassemia genes produce no beta)globin chainsome beta )thalassemia genes produce no beta)globin chains

and are termed beta) thalassemia.and are termed beta) thalassemia. 1ther beta )globin genes produce some beta )globin but in1ther beta )globin genes produce some beta )globin but in

diminished quantities and are termed betaL)thalassemia.diminished quantities and are termed betaL)thalassemia. ,ersons a4ected by beta )thalassemia may be hetero(ygous,ersons a4ected by beta )thalassemia may be hetero(ygous

or homo(ygous.or homo(ygous.

"etero(ygotes for most beta)thalassemia genes have beta)"etero(ygotes for most beta)thalassemia genes have beta)thalassemia minor.thalassemia minor.

5ost homo(ygotes have beta)thalassemia ma#or $Cooley&s5ost homo(ygotes have beta)thalassemia ma#or $Cooley&sanemia%! which is a severe transfusion)dependent anemia.anemia%! which is a severe transfusion)dependent anemia.

1ther homo(ygotes have a condition nown as thalassemia1ther homo(ygotes have a condition nown as thalassemiaintermedia that is more severe than thalassemia minor butintermedia that is more severe than thalassemia minor butnot generally transfusion)dependent.not generally transfusion)dependent.


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BETA-THALASSEMIABETA-THALASSEMIA Clinical &indin'$Clinical &indin'$ A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+ ,ersons with beta)thalassemia minor are usually,ersons with beta)thalassemia minor are usually

asymptomatic with a normal physical e/amination.asymptomatic with a normal physical e/amination. Those with beta)thalassemia ma#or are normal at Those with beta)thalassemia ma#or are normal at

birth but develop a signi'cant anemia during the 'rstbirth but develop a signi'cant anemia during the 'rstyear of life as fetal hemoglobin production decreases.year of life as fetal hemoglobin production decreases.– 2f the disorder is not identi'ed and treated with blood2f the disorder is not identi'ed and treated with blood

transfusions! such children develop massivetransfusions! such children develop massivehepatosplenomegaly and enlargement of the medullaryhepatosplenomegaly and enlargement of the medullary

space with thinning of the bony corte/.space with thinning of the bony corte/.– The seletal changes cause characteristic facial deformities The seletal changes cause characteristic facial deformities

$prominent forehead and ma/illa% and predispose the child to$prominent forehead and ma/illa% and predispose the child topathologic fractures.pathologic fractures.

– 2nadequate treatment causes poor growth and development2nadequate treatment causes poor growth and developmentin these children.in these children.


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BETA-THALASSEMIABETA-THALASSEMIA Clinical &indin'$Clinical &indin'$

0. =aboratory Findings>0. =aboratory Findings>

=aboratory 'ndings in beta)thalassemia=aboratory 'ndings in beta)thalassemia

minor include a normal or modestlyminor include a normal or modestly

decreased hemoglobin level.decreased hemoglobin level.

– The 5C3 is almost always decreased. The 5C3 is almost always decreased.

– The blood smear typically shows hypochromia! The blood smear typically shows hypochromia!target cells! and sometimes basophilic stippling.target cells! and sometimes basophilic stippling.

– "emoglobin electrophoresis is usually diagnostic"emoglobin electrophoresis is usually diagnostic

when hemoglobin A- or hemoglobin F or both iswhen hemoglobin A- or hemoglobin F or both is

elevated.elevated.


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BETA-THALASSEMIABETA-THALASSEMIA Clinical &indin'$Clinical &indin'$ 2nfants with beta)thalassemia ma#or are2nfants with beta)thalassemia ma#or are

hematologically normal at birth but develophematologically normal at birth but developsevere anemia after the 'rst few months of life.severe anemia after the 'rst few months of life.– The blood smear typically shows a severe The blood smear typically shows a severe

hypochromic! microcytic anemia with maredhypochromic! microcytic anemia with maredanisocytosis and poiilocytosis.anisocytosis and poiilocytosis.

– Target cells are prominent! and nucleated red blood Target cells are prominent! and nucleated red bloodcells often e/ceed the number of circulating whitecells often e/ceed the number of circulating white

blood cells.blood cells.– The hemoglobin usually falls to ?)* g8d= or less! and The hemoglobin usually falls to ?)* g8d= or less! and

the reticulocyte count is signi'cantly elevated.the reticulocyte count is signi'cantly elevated.– ,latelet and white blood cell counts may be,latelet and white blood cell counts may be

increased!increased!

– The serum bilirubin is elevated. The serum bilirubin is elevated.


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BETA-THALASSEMIABETA-THALASSEMIA Clinical &indin'$Clinical &indin'$ 2nfants with beta)thalassemia ma#or2nfants with beta)thalassemia ma#or

– The bone marrow shows mared erythroid The bone marrow shows mared erythroid

hyperplasia but is rarely needed for diagnosis.hyperplasia but is rarely needed for diagnosis.– "emoglobin electrophoresis shows only fetal and"emoglobin electrophoresis shows only fetal and

A- hemoglobin in children with homo(ygousA- hemoglobin in children with homo(ygousbeta)thalassemia.beta)thalassemia.

– Those with beta L)thalassemia genes mae Those with beta L)thalassemia genes maesome hemoglobin Al but have a mared increasesome hemoglobin Al but have a mared increasein fetal and in A- hemoglobin.in fetal and in A- hemoglobin.

– The diagnosis of homo(ygous beta)thalassemia The diagnosis of homo(ygous beta)thalassemiamay also be suggested by the 'nding of beta)may also be suggested by the 'nding of beta)

thalassemia minor in both parents.thalassemia minor in both parents.


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BETA-THALASSEMIABETA-THALASSEMIA T#!a%m!n%T#!a%m!n% 0eta)thalassemia minor requires no speci'c therapy but has0eta)thalassemia minor requires no speci'c therapy but has

important implications for genetic counseling.important implications for genetic counseling. For those with beta)thalassemia ma#or! two approaches toFor those with beta)thalassemia ma#or! two approaches to

treatment are now available>treatment are now available>– chronic transfusion with iron chelation or bone marrowchronic transfusion with iron chelation or bone marrow

transplantation.transplantation.– ,rograms of blood transfusion are generally targeted to maintain,rograms of blood transfusion are generally targeted to maintain

a nadir hemoglobin level above 77 g8d=.a nadir hemoglobin level above 77 g8d=.– "owever! maintenance of good health currently requires iron"owever! maintenance of good health currently requires iron

chelation with nightly subcutaneous infusion of defero/amine.chelation with nightly subcutaneous infusion of defero/amine.

– mall doses of supplemental ascorbic acid may enhance themall doses of supplemental ascorbic acid may enhance thee;cacy of iron chelation.e;cacy of iron chelation.– ,atients on chronic transfusion programs generally develop,atients on chronic transfusion programs generally develop

hypersplenism and require splenectomyhypersplenism and require splenectomy– 0one marrow transplantation is an important therapeutic option0one marrow transplantation is an important therapeutic option

for children with beta )thalassemia ma#orfor children with beta )thalassemia ma#or


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ENTYMES DE&ICIENCY ENTYMES DE&ICIENCY

G!n!#al con$id!#a%ion$G!n!#al con$id!#a%ion$ rythrocytes are dependent on the anaerobicrythrocytes are dependent on the anaerobic

metabolism of glucose for the maintenancemetabolism of glucose for the maintenanceof adenosine triphosphate $AT,% levelsof adenosine triphosphate $AT,% levels

su;cient for normal homeostasis.su;cient for normal homeostasis. Congenital de'ciencies of many $not all%Congenital de'ciencies of many $not all%

glycolytic pathway en(ymes have beenglycolytic pathway en(ymes have beenassociated with hemolytic anemias.associated with hemolytic anemias.

2n general! the morphologic abnormalities2n general! the morphologic abnormalitiespresent on the blood smear are nonspeci'c!present on the blood smear are nonspeci'c!and the inheritance of these disorders isand the inheritance of these disorders isautosomal recessive or M)lined.autosomal recessive or M)lined.


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ENTYMES DE&ICIENCY ENTYMES DE&ICIENCY G!n!#al con$id!#a%ion$G!n!#al con$id!#a%ion$ Thus! the possibility of a red cell en(yme defect Thus! the possibility of a red cell en(yme defect

should be considered during the evaluation of ashould be considered during the evaluation of acongenital hemolytic anemia whencongenital hemolytic anemia when

– the blood smear does not show red cell morphologythe blood smear does not show red cell morphologytypical of membrane or hemoglobin defects $eg!typical of membrane or hemoglobin defects $eg!spherocytes! sicle forms! target cells%!spherocytes! sicle forms! target cells%!

– when hemoglobin disorders are e/cluded bywhen hemoglobin disorders are e/cluded byhemoglobin electrophoresishemoglobin electrophoresis

– and when family studies do not suggest anand when family studies do not suggest anautosomal dominant disorder.autosomal dominant disorder.

– The diagnosis is con'rmed by 'nding a low level of The diagnosis is con'rmed by 'nding a low level ofthe de'cient en(yme.the de'cient en(yme. +*,D de'ciency and pyruvate inase de'ciency+*,D de'ciency and pyruvate inase de'ciency


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ENTYMES DE&ICIENCY ENTYMES DE&ICIENCY Clinical &indin'$Clinical &indin'$ A. ymptoms and igns>A. ymptoms and igns> 2nfants with +*,D de'ciency may have signi'cant2nfants with +*,D de'ciency may have signi'cant

hyperbilirubinemia and may require the use ofhyperbilirubinemia and may require the use of

phototherapy or e/change transfusionphototherapy or e/change transfusion 1lder children with +*,D de'ciency are asymptomatic1lder children with +*,D de'ciency are asymptomaticand appear normal between episodes of hemolysis.and appear normal between episodes of hemolysis.

"emolytic episodes are often triggered by infection or"emolytic episodes are often triggered by infection orby the ingestion of o/idant drugs! antimalarialby the ingestion of o/idant drugs! antimalarialcompounds and sulfonamide antibiotics.compounds and sulfonamide antibiotics.

2ngestion of fava beans may trigger hemolysis in2ngestion of fava beans may trigger hemolysis in5editerranean and Asian children5editerranean and Asian children

pisodes of hemolysis are associated with pallor!pisodes of hemolysis are associated with pallor! #aundice! hemoglobinuria! and sometimes #aundice! hemoglobinuria! and sometimescardiovascular compromise.cardiovascular compromise.


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Clinical &indin'$Clinical &indin'$ 0. =aboratory Findings>0. =aboratory Findings> The hemoglobin! reticulocyte count! and blood smear are The hemoglobin! reticulocyte count! and blood smear are

usually normal in the absence of o/idant)induced hemolysis.usually normal in the absence of o/idant)induced hemolysis. pisodes of hemolysis are associated with a variable fall inpisodes of hemolysis are associated with a variable fall in

hemoglobin.hemoglobin. 0ite cells or blister cells may be seen! along with a few0ite cells or blister cells may be seen! along with a few

spherocytes.spherocytes. "emoglobinuria is common! and the reticulocyte count"emoglobinuria is common! and the reticulocyte count

increases within a few days.increases within a few days. "ein( bodies may be demonstrated with appropriate stains."ein( bodies may be demonstrated with appropriate stains. The diagnosis is con'rmed by the 'nding of reduced levels of The diagnosis is con'rmed by the 'nding of reduced levels of

+*,D in erythrocytes.+*,D in erythrocytes. 0ecause this en(yme is present in increased quantities in0ecause this en(yme is present in increased quantities in

reticulocytes! the test is best performed at a time when thereticulocytes! the test is best performed at a time when thereticulocyte count is normal or near normalreticulocyte count is normal or near normal


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Clinical &indin'$Clinical &indin'$ ome common drugs and chemicals that canome common drugs and chemicals that can

induce hemolytic anemia in persons with +*,Dinduce hemolytic anemia in persons with +*,D

de'ciency.de'ciency.– AcetanilidAcetanilid– Nirida(oleNirida(ole– Do/orubicinDo/orubicin– NitrofurantoinNitrofurantoin– Fura(olidoneFura(olidone– ,hena(opyridine,hena(opyridine– 5ethylene blue5ethylene blue– ,rimaquine,rimaquine– Nalidi/ic acidNalidi/ic acid– ulfametho/a(oleulfametho/a(ole


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T#!a%m!n%T#!a%m!n% The most important issue is avoidance of drugs The most important issue is avoidance of drugs

nown to be associated with hemolysis.nown to be associated with hemolysis.

For some 5editerranean and Asian patients! theFor some 5editerranean and Asian patients! theconsumption of fava beans must also be avoided.consumption of fava beans must also be avoided.

2nfections should be treated promptly and2nfections should be treated promptly andantibiotics given when appropriate.antibiotics given when appropriate.

5ost episodes of hemolysis are self)limiting! but5ost episodes of hemolysis are self)limiting! butred cell transfusions may be lifesaving when signsred cell transfusions may be lifesaving when signsand symptoms indicate cardiovascularand symptoms indicate cardiovascularcompromise.compromise.

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ACUIRED HEMOLYTIC ANEMIAACUIRED HEMOLYTIC ANEMIA

AUTOIMMUNE HEMOLYTIC ANEMIAAUTOIMMUNE HEMOLYTIC ANEMIA

G!n!#al Con$id!#a%ion$G!n!#al Con$id!#a%ion$ Acquired autoimmune hemolytic anemia isAcquired autoimmune hemolytic anemia is

more common causes of acute anemiamore common causes of acute anemia

after the 'rst year.after the 'rst year. 2t may arise as2t may arise as– an isolated probleman isolated problem

– or may complicateor may complicate

an infection $hepatitis! upper respiratory tractan infection $hepatitis! upper respiratory tractinfections! mononucleosis! cytomegaloviras infection%!infections! mononucleosis! cytomegaloviras infection%!

systemic lupus erythematosussystemic lupus erythematosus

other autoimmune syndromesother autoimmune syndromes

or immunode'ciency states.or immunode'ciency states.

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Clinical &indin'$Clinical &indin'$ A S)m*%om$ and Si'n$+A S)m*%om$ and Si'n$+

– The disease usually has an acute onset! The disease usually has an acute onset!

presenting with weaness! pallor! and fatigue.presenting with weaness! pallor! and fatigue. Gaundice is a prominent 'nding! and Gaundice is a prominent 'nding! and

splenomegaly is often present.splenomegaly is often present.

– ome cases are chronic and insidious inome cases are chronic and insidious in

onset.onset.– Clinical evidence of the underlyingClinical evidence of the underlying

disease may be present.disease may be present.

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AUTOIMMUNE HEMOLYTIC ANEMIAAUTOIMMUNE HEMOLYTIC ANEMIA B La,o#a%o#) &indin'$+B La,o#a%o#) &indin'$+

– The anemia is normochromic and normocytic and may vary The anemia is normochromic and normocytic and may varyfrom mild to severe $hemoglobin concentration O? g8d=%.from mild to severe $hemoglobin concentration O? g8d=%.

– The reticulocyte count is usually increased but occasionally The reticulocyte count is usually increased but occasionallymay be normal or low.may be normal or low.

– pherocytes and nucleated red cells may be seen on thepherocytes and nucleated red cells may be seen on theperipheral smear.peripheral smear.– Although leuocytosis and elevated platelet counts are aAlthough leuocytosis and elevated platelet counts are a

common 'nding! thrombocytopenia is occasionally seen.common 'nding! thrombocytopenia is occasionally seen.– 1ther laboratory data consistent with hemolysis are present1ther laboratory data consistent with hemolysis are present

such as increased indirect and total bilirubin! lacticsuch as increased indirect and total bilirubin! lacticdehydrogenase $=D"%! aspartate transaminase $AT%! anddehydrogenase $=D"%! aspartate transaminase $AT%! andurinary urobilinogen.urinary urobilinogen.

– The hemolysis is intravascular if there is hemoglobinemia or The hemolysis is intravascular if there is hemoglobinemia orhemoglobinuria.hemoglobinuria.

– /amination of bone marrow shows a mared erythroid/amination of bone marrow shows a mared erythroidhyperplasia.hyperplasia.

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AUTOIMMUNE HEMOLYTIC ANEMIAAUTOIMMUNE HEMOLYTIC ANEMIA B La,o#a%o#) &indin'$+B La,o#a%o#) &indin'$+ erologic studies provide important informationerologic studies provide important information

– 2n almost all cases the direct and indirect antiglobulin2n almost all cases the direct and indirect antiglobulin$Coombs&% test are positive.$Coombs&% test are positive.

– Further evaluation allows distinction of three syndromes.Further evaluation allows distinction of three syndromes. The presence of 2g+! ma/imal in vitro activity at 9@JC! and The presence of 2g+! ma/imal in vitro activity at 9@JC! andeither no antigen speci'city or an 6h)lie speci'cityeither no antigen speci'city or an 6h)lie speci'cityconstitute warm autoimmune hemolytic anemia withconstitute warm autoimmune hemolytic anemia withe/travascular destruction by the reticuloendothelial system.e/travascular destruction by the reticuloendothelial system.

The detection of complement alone and optimal reactivity in The detection of complement alone and optimal reactivity invitro at JC with i antigen speci'city are diagnostic of coldvitro at JC with i antigen speci'city are diagnostic of coldautoimmune hemolytic anemia with intravascular hemolysis.autoimmune hemolytic anemia with intravascular hemolysis.

,aro/ysmal cold hemoglobinuria appears identical with cold,aro/ysmal cold hemoglobinuria appears identical with coldautoimmune hemolytic anemia but has a di4erent antigenautoimmune hemolytic anemia but has a di4erent antigenspeci'city and e/hibits hemolysis as well as agglutination inspeci'city and e/hibits hemolysis as well as agglutination invitro.vitro.

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AUTOIMMUNE HEMOLYTIC ANEMIAAUTOIMMUNE HEMOLYTIC ANEMIA T#!a%m!n%T#!a%m!n% 5ost patients with warm autoimmune hemolytic5ost patients with warm autoimmune hemolytic

anemia $in which hemolysis is e/travascular%anemia $in which hemolysis is e/travascular%respond the prednisone.respond the prednisone.

,atient may respond to - g of intravenous immune,atient may respond to - g of intravenous immuneglobulins $2+23% per ilogram for 7)9 days! but fewerglobulins $2+23% per ilogram for 7)9 days! but fewerpatient respond to 2+23 than to prednisone.patient respond to 2+23 than to prednisone.

Although the rate of remission with splenectomyAlthough the rate of remission with splenectomymay be as high a ?! particularly in warmmay be as high a ?! particularly in warmautoimmune hemolytic anemia! this approach shouldautoimmune hemolytic anemia! this approach should

be withheld until other treatments have been tried.be withheld until other treatments have been tried. 2n severe cases unresponsive to more conventional2n severe cases unresponsive to more conventionaltherapy! immunosuppressive agents such astherapy! immunosuppressive agents such ascyclophosphamide! a(athioprine or busulfan may becyclophosphamide! a(athioprine or busulfan may betried alone or in combination with corticosteroids.tried alone or in combination with corticosteroids.

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ACUIRED HEMOLYTIC ANEMIA

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T#!a%m!n%T#!a%m!n% upportive therapy is crucial.upportive therapy is crucial. ,atients with cold)reacting antibodies! particularly,atients with cold)reacting antibodies! particularly

paro/ysmal cold hemoglobinuria! should be eptparo/ysmal cold hemoglobinuria! should be ept

in a warm environment.in a warm environment. Transfusion may be necessary because of the Transfusion may be necessary because of the

complications of severe anemia but should becomplications of severe anemia but should beused only when there is no alternative.used only when there is no alternative.

,atients with severe intravascular hemolysis may,atients with severe intravascular hemolysis mayhave associated disseminated intravascularhave associated disseminated intravascularcoagulation $D2C%! and heparin therapy should becoagulation $D2C%! and heparin therapy should beconsidered in such cases.considered in such cases.

curs 13 sem 2

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