In autoimmune hemolytic anemia (AIHA) RBCs are destroyed by antibodies
made by a person against their own RBCs.
AIHA is divided into two types: an IgG or "warm" type (optimally active
at 37oC) and an IgM or "cold" type (optimally active at 4oC).
In AIHA the antibody coated RBC membrane is removed bit by bit, usually
in the spleen. As this happens the cell becomes increasingly spherical
maintaining essentially the same volume.
AIHA varies in severity and often waxes and wanes. Splenomegaly is
Before going further, be sure you understand the direct antiglobulin
The DAT detects antibodies attached to the patient's RBCs. This is
important for classifing and understanding the immune hemolytic anemias.
The DAT is also known as the direct Coombs test.
The detection of free antibodies against RBCs in the patient serum
requires the use of the indirect Coombs test. You should review this
Warm AIHA, the most common type of immune hemolytic anemia is mediated
by IgG autoantibodies against RBC surface antigens (active at 37°
Non-Hodgkin's Iymphomas, Hodgkin's disease, and autoimmune disorders
(rheumatoid arthritis; SLE), and drugs (methyl dopa) are common causes
of warm AIHA; however, most cases are idiopathic.
In addition to the usual findings associated with hemolytic anemia
(RBC polychromasia, increased unconjugated bilirubin,
Decreased haptoglobin, and hemoglobinuria) there is prominent spherocytosis
on the PBS and a positive DAT (direct Coombs' test).
Cold AIHA or cold agglutinin disease, caused by IgM antibodies most
active at <30oC, is a hemolytic anemia characterized by
RBC agglutination and hemolysis in acral cold exposed areas of the body.
An IgM complement fixing antibody binds to RBCs at 28-31oC.
The fixed complement causes intravascular hemolysis. As RBCs are warmed
in the central organs the bound IgM is lost leaving only bound C3 (DAT
positive only for C3).
Cold agglutinin disease is associated with Iymphoma (antibodies
against anti-i), Mycoplasma pneumonia (antibodies against anti-I), and
rarely infectious mononucleosis (antibodies against anti-i).
People with cold agglutinin disease have a chronic hemolytic anemia
with periods of jaundice, and hemoglobinuria.
Cold agglutinin disease with RBC agglutination may be associated with
Laboratory findings in cold agglutinin disease are similar to warm
AIHA (RBC polychromasia, increased unconjugated bilirubin, decreased
haptoglobin, and hemoglobinuria), but usually with less spherocytosis.
In many cases agglutination of RBCs is seen on peripheral blood smears
(room temperature). C3 is found only on the RBC surface by the DAT.
AIHA in association with idiopathic thrombocytopenic purpura (ITP)
is known as Evans syndrome.
Treatment of AIHA, warm or cold, includes: 1) treatment of the underlying
disease, 2) discontinue offending drugs, and 3) corticosteroids (Prednisone).
Agglutination of erythrocytes is seen on this peripheral blood
Transfusion of ABO incompatible blood and Rh (rhesus) -disease of
the newborn are the two most common examples of antibody produced by
one person reacting with RBCs of another.
Allogeneic transplantation (renal, hepatic, cardiac and bone marrow)
can cause a hemolytic anemia due to donor-derived RBC antibodies produced
in the recipient by donor lymphocytes.
Immune hemolytic anemias are commonly drug related.
Two well defined mechanisms by which a drug can cause a hemolytic anemia
are: 1) antibody against a drug-RBC membrane complex (penicillin), and
2) complement activation following a drug-protein complex on the RBC
(quinidine). In each, the hemolytic anemia gradually disappears when
the drug is discontinued.
A third mechanism is that in which a drug induces a warm AIHA, possibly
by drug (Methyldopa) induced inhibition of T-suppressor allowing uninhibited
autoantibody production by B cells. Despite drug withdrawal, antibodies
may remain for months.
Of the drug related immune hemolytic anemias which result in an intravascular
A. the hapten formation mechanism
B. the immune complex mechanism
C. the autoimmune mechanism
D. both the immune complex and autoimmune mechanisms
E. both the hapten and immune complex mechanisms
Infections may initiate a hemolytic crisis in G-6-PD deficiency
or in cases of meningcoccal or pneumococcal septicemia cause a microangiopathic
hemolytic anemia. Intravascular and extravascular hemolysis of infected
RBCs may occur in malaria.
Drugs and toxins may cause intravascular hemolysis through the formation
of Heinz bodies resulting in damaged membranes thus destroying RBCs.
Lead and arsenic poisoning often cause hemolysis.
Severe thermal burns damage RBCs forming acanthocytes, schistocytes,
RBC survival may be shortened in renal failure (burr cells) and in
liver disease (acanthocytes and target cells).
Numerous spherocytes and a few schistocytes in the PBS from
a patient suffering from severe burns.
Hemolytic disease of the newborn (erythroblastosis fetalis)
is secondary to maternal alloimmunization to fetal RBC antigens (maternal
antibodies cross the placenta; react with fetal RBCs and cause a fetal
Most commonly, the mother is Rh-type d and the fetus Rh-type D.
Hemolytic disease of the newborn may be due to ABO incompatibility,
where the mother is blood group O and the infant is blood group A or
Hemolytic disease of the newborn may cause stillbirth, fetal heart
kernicterus (bilirubin staining of basal ganglia and other CNS structures)
leading to neurologic damage.
Hemolytic disease of the newborn is relatively uncommon because of
routine administration of anti-D IgG antiserum (removes fetal RBCs from
the maternal circulation; prevents maternal alloimmunization) of D-negative
mothers at the time of delivery of a D-positive infant.
Photo courtesy Thomas C Bithell, M.D.
In the rare paroxysmal cold hemoglobinuria, the antibodies
Landsteiner) are IgG and are against the P blood group antigens.
Such antibodies are usually associated with viral infections (measles
and mumps) and usually found in children without lasting sequale.
Acute hemolysis results when warming follows exposure to the cold.
The lysis is complement induced and takes place in warm conditions following
antibody - RBC binding in the cold.
Under no circumstances should you share any material downloaded from Student Source course websites with individuals outside the class. Under no circumstances should you repost material downloaded from Student Source to other websites. Some of our pages are restricted to UVa School of Medicine users and require an Oasis account for access.