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HEMOLYTIC ANEMIA
EXTRACORPUSCULAR
DEFECTS
DR. SWAMY C.R.
Anemia resulting from an increase in the rate of red cell destruction.
CAUSES:
I.Immune
A.
•
•
•
B.
c.
A. Isoimmune
Hemolytic disease of the newborn
incompatible blood transfusion
B. Autoimmune: lgG only; c’3 only; mixed lgG and C’3
1.
Idiopathic
a.Warm antibody
b. Cold antibody
c. Cold – warm (Donath – Landsteiner antibody)
SECONDARY:
a. Infection, viral: Infectious mononucleosis
(Epstein – Barr virus (EBVI), kcytomegalovius
(CMV), hepatitis, herpes simplex, measles,
varicella, influenza A, coxsackie B, human
immunodeficiency virus (HIV), bacterial;
streptococcal, typhoid fever, Escherichia coli
sapticemia; Mycoplasma pneumoniae (atypical
pneumonia).
b.Drugs and chemicals: quinine, quinidine,
phenacetin, p-aminosalicylic acid, Sodium
cephalothin (Keflin), penicillin, tetracycline,
rifampin,sulfonamides,chlorpromazine,pyramidon,
dipyrone, insulin
 c.Hematologic disorders: leukemias, lymphomas,
lymphoproliferative
syndrome,
thrombocytopenic purpura (Evans
paroxysmal
cold
hemoglobinuria,
noctumal hemoglobinuria
idiopathic
syndrome),
paroxysmal
 d.
Immunopathic disorders: Systemic lupus
erythematosus, perirteritis nodosa, scleroderma,
dermatomyositis, rheumatoid arthritis, ulcerative
colitis,
agammaglobulinemia,
Wiskott
Aldrich
syndrome, dysgammaglobinemai igA deficiency,
thyroid disorders
 e.
Tumors : ovarian teratomate, dermods

Nonimmune
A. Idiopathic
B. Secondary
 1. Infection, viral; infectious mononucleosis, viral
hepatitis; bacterial; streptococcal, E.coli septicemia,
clostridium perfringens, Bartonella bacilliformis;
parasites; malaria, histoplasmosis.
 2. Drugs: phenylhydrazine, vitamin k, benzene,
nitrobenzene
sulfones,
lead
phenacetin,
acetinalimide
 3. Hematologic
disorders: leukemia, aplastic
anemia, megaloblastic anemia, bypersplenism,
pyknocytosis
 Microangiopathic hemolytic anemia: thrombotic
thrombocytopenic purpura, hemolytic uremic
syndrome, chronic relapsing schestocytstic
hemolytic anemia, burns, postcardiac surgery,
march hemoglobinuria.
 Miscellaneous: Wilson’s disease, erythropoietic
porphyria, osteopetrosis, hypersplenism
 HEMOLYTIC DISEASE OF THE NEWBORN
 Immune hemolysis occurring in the fetus as a result of
the transplacental passage of maternal antibody directed
against a fetal red cell antigen that is not shared by the
mother. The antibody is the product of the normal immune
response to a foreign substance and is invariably of the
lgG type, although hemolytic disease of the newborn
caused by ABO incompatibility always has been more
common than that caused by Rh incompatibility, ABO
hemolytic disease is usually less severe and has not been
associated with fetal and neonatal death or significant
sequelae to the extent that Rh hemolytic disease has.
 The spectrum of pathologic conditions resulting from
minimal anemia or hyperbilirubinemia to hydrops fetalis.
 ETIOLOGY AND PATHOGENESES
 
Rh disease is most significant clinically because
of its severity, although ABO hemolytic disease is
about twice as common.
 
The passage of fetal red cells across the
placenta into the maternal circulation may result in
the production of antibodies against fetal red cell
antigens recognized by mother as “not self” .
 
The introduction of a sensitive acid elution
technique for identifying fetal cells by the
demonstration of intracellular Hb F enabled the
detection of 0.05 ml of fetal blood in the maternal
circulation.
The gestational are at which fetal maternal
transplacental leakage of red cells begins is uncertain, The
volume of fetal blood that at any one time enters the
maternal circulation during a normal pregnancy is small,
probably less than 0.1 ml.
It is during delivery that larger boluses, greater than 0.2
ml, enter the maternal circulation.

It is these larger fetal maternal hemorrhages that
stimulate the production of antibody Immunology fetal maternal
bleeds may occur in spontaneous or induced abortions.
Entopic pregnancy, cesarean section and manual removal of
the placenta. The risk of sensitization is related to the volume
of the fetal maternal bleed ing.

In general the larger the fetal – maternal hemorrhage, the
greater the incidence of demonstrable sensitization. Since
sensitization occurs most frequently during birth, the most
accurate indicator for sensitization is the demonstration of
maternal antibodies during the succeeding pregnancy, The
incidence of sensitization at the end of the second pregnancy is
about 17% in ABO compatible mothers.

 CLINICAL FEATURES
 § Jaundice – Noted with in the first 24 hrs after birth




and in untreated infants reaches maximal levels
§ Immune hemolysis and anemia
§ Encephalopathy (kernicterus) – Caused by the
effects of unconjugated bilirubin on the central
nervous system.
§ Purpura associated with thrombocyutopenia
§ Hypoglycemia -is frequently noted in severally
affected infants.
 INVESTIGATOINS
 
Peripheral blood – Evidence for increased red
cell destruction is the degree of anemia,
reticulocytosis, and normoblasas, polychromasia and
anisocytosis, intense leukocytosis may be seen in
severely affected infants.
 
Bone marrow – Erythroid hyperplasia is
invariably present.
 
Immunologic evaluation – The diagnosis is
established if red cells from an Rh positive infant born
to an Rh negative mother give a positive direct
antiglobulin test.
 
Serum bilirubin - Cord bilirubin levels are not
high and levels in excess of 4 mg/dl are evidence of
severe disease.

 THERAPY
 Prevention of Rh isosensitization




- Routine
administration of Rh immune globulin to all
unsensitized Rh-negative mothers who have given
birth to an Rh-positive infant or who have had a
spjontaneous or induced abortion.
Administration of 300 micro grams of Rh immune
globulin intramuscularly to all unsensitized Rhnegative women within 72 hours of the delivery of an
Rh-positive infant. In cases in which Rh immune
globulin has not been given within 72 hours, it should
be administered late rather than withheld.
After abortion – less than 12 weeks gestation, 50
micro grams more than 12 weeks gestation, 100
micro grams
After amniocentesis – 50 micro grams (depending
on amount of fetomaternal hemorrhage)
After ruptured – ectopic pregnancy or manual
version, 10 to 15 micro grams ml fetal blood.
 TREATEMENT OF THE AFFECTED INFANT
 v
Major objectives : 1). Prevention of intrauterine





fetal death 2) prevention of bilirubin encepkjhalopathy
in the live born infant.
v
Prevention of intrauterine fetal death : The
developing fetus s at risk from severe anemia, not
from hyperbilirubinemia, since the placenta effectively
clears this substance. Therapy of the severely
affected fetus is directed therefore solely toward
correcting the severe anemia.
v
Prevention of bilirubin encephalopathy Exchange transfusion : The volume of an exchange
transfusion is usually calculated at two times the
blood volume of the exchanged infant. Or about 160
ml/kg.
Phototherapy :
ABO HEMOLYTIC DISEASE OF THE NEWBORN
A reported to Cause of about two thirds of the
cases of hemolytic disease of the newborn. It differs
from Rh hemolytic disease primarily in the degree of
severity. Severe hyperbilirubinemia is unusual and
hyudrops fetalis extremely rare. The pathophysiology of
ABO hemolytic disease is identical to that to Rh
disease. The antibody causing the immune destruction
is of the lgG class. Since igM anti – A or anti-B cannot
cross the placenta.
ABO hemolytic disease is restricted almost to
tally to group A or B infants born to group O mothers.
The reason for the lack of clinical disease are not
completely known. However, certain factors may affect
the interaction of anti –A with A cells in the fetus and
newborn.
A weakly Positive direct antiglobulin test on cord
blood or newborn blood may be found.
3.
free anti – A or anti –B may be demonstrated in the
serum of the newborn.
4.
Confirmatory evidence is the presence of lgG anti
–A or and –B in the maternal serum.
2.
TREATMENT
Therapy of severe ABO hemolytic disease is
similar to that of Rh hemolytic disease. In the
frequently occurring mild cases phototherapy or
phenobarbital therapy can be given.
WARM AUTOIMMUNE HEMOLYTIC ANEMIA
Antibodies of the lgG class arWARe most
commonly responsible for AIHA in children. The
antigen to which the lgG antbody is directed is one of
the Rh erythrocyle antigens in more than 70% of
cases. The antibody usually has its maximal activity at
37%C, and resultant hemolysis is called warm
antibody-induced hemolytic anemial. Rarely, warm –
reacting lgM antibodies may be responsible.
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Clinical Features
1. Severe, life-threatening condition
2. Sudden onset of pallor, jaundice, dark urine
3. Splenomegaly
4. Laboratory findings.
a. Hemoglobin level: may be very low
b. Marked reticulocytosis is very common
c. Smear: prominent spherocytes, polychromasia,
macrocytes, autoagglutination
 d. Neutropenia and thrombocytopenia (occasionally)
 e. Increased osmotic fragility and autohemolysis
proportional to sphero cytes
Direct coombs test positive
•
b. Hyperbilirubinemia
• c.
Haptoglobin level is usually markedly
decreased
• d.
Hemoglobinuria, increased urinary
urobilinogen
•
•
a.
MANAGEMENT
Because this is a life-theatening condition, the
following parameters must be monitored carefully.
1.
Hemoglobin level (q4h)
2.
Reticulocyte count (daily)
3.
Splenic size (daily)
4.
Hemoglobinuria (daily)
5.
Haptoglobin level (weekly)
6.
Coombs test (weekly
TREATMENT
1.
Blood transfusion
a.
If specific antibody is identified, compatible donor
may be selected.
b.
Washed packed red cells should be used
c.
The volume of transfused blood should only be of
sufficient quantity to relieve any cardiopulmonary
embarrassment from the anemia.
2.
Corticosteriod therapy.
a.
Hydrocortisone 8-40 mg/day IV in divided
doses (q8h) or prednisone 2-10 mg/day PO is
administered.
a.
High dosage corticosteroid therapy should be
maintained for several days. Threafter, corticosteroid
therapy in the form of prednisone should be slowly
tapered off over a 3 to 4 week period.
3.Plasmapheresis
has been successful in slowing the rate of hemosysis in
patients with severe IgG- induced immune hemolytic
anemia. Success is limited, possibly because more than
half of the IgG is extravascular and the plasma contains
only small amounts of the antibody ; most of the antibody
is on the red cell surface.
4.Intravenous gamma globulin (IVGG) in a dose of 5
gm/kg,
5.splenectomy: Indicated if the hemolytic process
continues to be brisk despite highdosage corticosteroid
therapy and intravenous gamma globulin for 3-4 weeks.
Cytoxic Agents
a.
Antimetabolites : azathioprine, 6mercaptopurine, and thiroguanine
b.
Alkylating agents: chlorambucil and
cyclophosphamide.
c.
Mitotic inhibitos: vincristine and vinblastine
6.
7.
Immunosuppressive therapy: Cyclosporine
8.
Hormonal therapy : danazol, (synthetic
androgen). which has a masculinizing effect. Appears to
be due to decreased expression of macrophage Fcy
receptor activity;
COLD AUTOIMMUNE HEMOLYTIC ANEMIA
IgM antibodies are found less often in association
with hemolysis in the pediatric age group. The destruction
of red blood cells is usually triggered by cold exposure.
Cold hemagglutinin disease usually occurs during 1.
Mycoplasma pneumoniae infection
2. Infectious
mononucleosis, 3. cytomegalovirus
4. mumps..
CLINICAL FEATURES
Similar to those in warm autoimmune hemolytic
anemia but are less marked.
TREATMENT
Treatment consists of control of the underlying
disorder. 1. Blood Transfusions may be necessary ;
warming the blood to 370 C during administration by means
of a heating coil or water bath is indicated to avoid further
temperature activation of antibody.
If the anemia is severe, a trial of cytotoxic drug
therapy is appropriate. Alkylating agents such as
cyclophosphamide and chlorambucil.
Treatment with
corticosteroids or splenectomy is generally not effective.
Plasmapheresis is a valuable approach to reducing the
level of cold agglutinins.
DONATH LANDSTEINER COLD HEMOLYSIS
An unusual igG antibody with anti –P specificity, is
responsible. This antibody, although uncommon, is most
frequently found in children with viral infections. Hemolysis
in this syndrome is most commonly intravascular as a
result of the unusual complement activating efficiency of
this IgG antibody. Hemolysis, which is usually mild, may
occasionally be severe but resolves as the infection clears.
MICROASGIOGRAPHIC HEMOLYTIC ANEMIA
The blood smear is characterized by the presence
of buu erythrocytes, schistocytes, helmet cells, and
microspheocytes.
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