Pathology Patterns Reviews

Am J Clin Pathol 2006;125(Suppl 1):S71-S77 S71

DOI: 10.1309/ABP0B54GQL74L3KW S71
American Society for Clinical Pathology
A b s t r a c t
Although some autoantibodies do not cause hemolysis
and their workup is performed routinely, others might
lead to life-threatening hemolysis. In the latter
situation, the pathologist often is involved in the urgent
decision to transfuse before completion of the
evaluation. However, every effort must be made to
exclude the presence of concurrent alloantibodies. This
identification of RBC autoantibodies is less common
than alloantibody identification, and the evaluation
often requires techniques and expertise available only
in specialized laboratories. Unlike emergency release of
units for trauma victims, an autoantibody by definition
will react with all units in the inventory; thus, all
crossmatches are expected to be incompatible. To avoid
additional untoward consequences of transfusion, there
has to be close communication between the consulting
pathologist and the clinician, including close
monitoring of the patient during and after transfusion.
This review is intended to serve as a guide to general
pathologists in the appropriate evaluation and
interpretation of laboratory tests in the diagnosis and
management of autoimmune hemolytic anemia.
Clinical Features
There are 2 main types of autoimmune hemolytic ane-
mia (AIHA). The warm type is secondary to IgG anti-RBC
antibodies that optimally bind at core body temperature
(37C) and is much more common than cold AIHA. In cold
AIHA, the antibody belongs to the IgM class and reacts more
strongly at 4C. Cold AIHA is also known as cold agglutinin
disease (CAD).
Warm AIHA is associated with nonspecific signs and
symptoms. The clinical syndrome is related largely to the
degree of anemia. As with anemia of any origin, when severe,
patients may complain of reduced exercise tolerance and
fatigue or show signs of congestive heart failure. The excep-
tion is acute intravascular hemolysis. This is seen classically
in patients who receive incompatible blood products (acute
hemolytic transfusion reaction) but can be seen rarely in
patients with AIHA. When associated with transfusion,
patients may complain of fever, chills, severe back pain, or
pain at the infusion site. In AIHA, sudden and brisk hemol-
ysis is associated with severe fatigue, dyspnea, and jaundice.
Patients with cold AIHA also may have symptoms
related to in vivo destruction of RBCs when exposed to cold
ambient temperatures. This often will manifest as a purple-
gray discoloration of the skin on distal body parts such as
the fingers, toes, nose, and ears. The discoloration usually
resolves by warming the body, but it can progress to ischemic
necrosis in severe cases.
History and Physical Examination
Because the majority of hemolytic anemias are related to
an underlying disease state, a careful history and physical
Laboratory Evaluation and Transfusion Support of Patients
With Autoimmune Hemolytic Anemia
John E. Reardon, MD, and Marisa B. Marques, MD
Key Words: Autoimmune hemolytic anemia; Direct antiglobulin test; DAT; Elution; Adsorption
DOI: 10.1309/ABP0B54GQL74L3KW
Reardon and Marques / TESTING AND TRANSFUSION SUPPORT IN AIHA
S72 Am J Clin Pathol 2006;125(Suppl 1):S71-S77
S72 DOI: 10.1309/ABP0B54GQL74L3KW
American Society for Clinical Pathology
examination are necessary. A thorough medication history
also is essential because drugs such as penicillin may trigger
such autoimmune responses. Careful attention to ethnicity
and family background are important. Physical examination
findings may include jaundice, icterus, pallor, resting tachy-
cardia, and splenomegaly.
Initial Laboratory Evaluation
AIHA may be suspected when signs of increased RBC
destruction (anemia with microspherocytosis and reticulocy-
tosis, hyperbilirubinemia, elevated serum lactate dehydroge-
nase level, and decreased or absent haptoglobin) are noted in
the initial laboratory evaluation of a patient with unexplained
anemia Image 1. A positive direct antiglobulin test (DAT)
or direct Coombs test result is the sine qua non criterion for
the diagnosis of AIHA and helps distinguish it from other
causes of increased RBC turnover, such as membrane or
hemoglobin defects. However, between 1% and 2% of hospi-
talized patients have a positive DAT result without signs or
symptoms of hemolysis.
1
Thus, the predictive value of a
positive result is low for the diagnosis of AIHA, and clinical
correlation is paramount to understanding the significance of
a positive DAT result.
2
Several mechanisms have been proposed to explain
the differences in hemolytic potential of autoantibodies,
including the following: (1) antibody subclass, (2) interac-
tion with Fc receptors, (3) ability to activate complement, (4)
concentration of antibody and corresponding antigen mole-
cules on the RBC surface, and (5) immune regulation of
autoreactive immunoglobulins.
3
Direct Antiglobulin Test
The DAT is performed by incubating the patients washed
RBCs with a polyspecific antibody that recognizes human IgG
and C3.
4
It has been shown repeatedly that agglutination of
the patients cells (positive test result) will occur if there are
as few as 200 to 500 molecules of IgG per cell. When the
polyspecific DAT result is positive, the laboratory should
perform a split DAT in which the patients RBCs are incu-
bated with antibodies specific for IgG or C3. A positive DAT
result for IgG confirms the diagnosis of warm AIHA; it
determines that the antibody bound at body temperature or
37C. The DAT in warm AIHA most often is positive for IgG
only because the antibody is not as efficient at activating
complement as is IgM. Less commonly, patients with warm
AIHA have a DAT result with dual positivity (IgG and C3);
C3 alone is the least likely finding.
1
The strength of the agglutination response in the DAT
also is of interest because stronger DAT responses (2+ to 4+)
denote higher antibody density on the RBC surface and are
more likely to be associated with hemolysis. As reported by
Wheeler et al,
1
86% of patients with a positive DAT result
who experienced hemolysis had 2+ or stronger agglutination
when the sample was incubated with anti-IgG.
1
The authors
also found a direct correlation between immune hemolysis
and the presence and amount of C3 on the RBC membrane.
1
The same conclusion was reached in another recent study, by
Wikman et al,
3
in which severe hemolysis was associated
with strongly positive DAT results. Comorbid conditions also
have been shown to correlate with the risk of hemolysis in
patients with positive DAT results. Almost 70% of patients
with hemolytic anemia had diseases classically associated
with AIHA, such as immune thrombocytopenic purpura and
hematologic malignancies.
1
A small percentage of cases of AIHA have negative
results of the DAT and antibody screen.
5
Possible explana-
tions for these findings include the following: (1) low num-
ber of IgG molecules per RBC, (2) IgA and IgM autoanti-
bodies, and (3) autoantibodies with low affinity. Before
implicating such less common possibilities, however, other
reasons for the negative result should be considered. A DAT
result may be falsely negative as a consequence of technical
difficulties in performing the test. Thus, in the presence of a
Image 1 Peripheral smear of a patient with warm
autoimmune hemolytic anemia associated with chronic
lymphocytic leukemia who had a hemoglobin level of 6.8
g/dL (68 g/L) and a hematocrit value of 19% (0.19) during an
acute hemolytic crisis. Her polyspecific direct antiglobulin
test result was 3+; IgG, 3+; C3, 2+; total bilirubin, 4.6
mg/dL (79 mol/L; direct, 0.3 mg/dL [5 mol/L]; and indirect,
4.3 mg/dL); and lactate dehydrogenase, 713 U/L. Note the
large number of microspherocytes and immature RBCs,
including nucleated forms and reticulocytes, consistent with
immune-mediated hemolysis (Wright stain, 1,000).
(Courtesy of Vishnu V.B. Reddy, MD, Department of
Pathology, University of Alabama at Birmingham).
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Am J Clin Pathol 2006;125(Suppl 1):S71-S77 S73
DOI: 10.1309/ABP0B54GQL74L3KW S73
American Society for Clinical Pathology
negative result that does not agree with the clinical picture,
the DAT should be repeated by an experienced technologist
before a final conclusion is reached. If the DAT result is
confirmed as negative by the usual technique, coating of the
patients RBCs by IgG and/or complement can be assessed
by more specialized techniques such as flow cytometry and
the direct polybrene test.
5
However, 50% of the time, DAT-
negative AIHAs are never explained even after extensive
laboratory evaluation. Patients with such a diagnosis seem to
respond to conventional AIHA approaches.
A positive DAT result for C3 only is seen classically in
CAD, a process mediated by an IgM autoantibody capable of
causing brisk intravascular hemolysis through complement
activation. Although CAD is less common than warm AIHA,
it presents a different set of laboratory and transfusion require-
ments (see Thermal Amplitude Test). Alternatively, drugs
such as quinidine and ceftriaxone can induce warm AIHA
via the formation of immune complexes with drug-specific
antibodies in the serum, causing complement activation in
the vicinity of RBCs and a DAT result positive for C3 only.
Elution
To confirm that the positive DAT result is due to an
autoantibody, an elution of the bound IgG should be
performed. The cold-acid elution method is the most
commonly used in the United States.
4
A very important tech-
nical aspect of the test is to thoroughly wash the patients
RBCs before the elution to eliminate interference by anti-
body from the plasma. The subsequent eluate of concen-
trated IgG removed from the RBCs then should be incubated
with reagent RBCs to check for its specificity. Most autoanti-
bodies react with the full panel with similar agglutination
strengths, for they usually bind to an antigen present in all cells.
Less commonly, the antibody may show a relative specificity
within the Rh system such as for the e antigen. There does not
seem to be a correlation between the autoantibody specificity
and its hemolytic potential.
3
If the DAT result is only weakly
positive, the eluate may not react with the reagent cells. Elu-
tion is particularly important if the patient had received a
transfusion in the recent past and the DAT result is not very
strong or if mixed field agglutination is noted when the cells
are inspected microscopically. Such findings point to an allo-
antibody bound to the still circulating transfused RBCs
instead of an autoantibody attached to the patients own
cells. In cases of a positive DAT result owing to an alloanti-
body, the eluate should react only with selected reagent cells
containing the antigen recognized by the antibody.
Antibody Screen or Indirect Coombs Test
The counterpart of the DAT is the antibody screen or
indirect Coombs assay. Most patients with AIHA will have
positive results to the screen and a pan-reactive antibody
panel owing to residual autoantibody in the patients serum.
1
In patients in whom an autoantibody was not suspected and a
DAT not ordered, a pan-reactive panel and a positive auto-
control result should trigger the performance of the DAT.
When all of the autoantibody is RBC-associated (negative
screen result), it is possible to provide crossmatched compat-
ible units if transfusion is indicated. In the majority of pa-
tients with AIHA, however, the autoantibody also is reactive
in the serum, and further workup is mandatory to provide the
safest possible product.
Autoadsorption
A serum sample containing a warm autoantibody that
reacts with the full panel needs to be evaluated further for the
concomitant presence of RBC alloantibodies. Patients who
have ever been pregnant and/or received transfusion are at
risk of having been sensitized to nonself RBC antigens in
addition to having a concurrent autoantibody. Published data
on 647 patients serum samples with AIHA demonstrated
alloantibodies in 32% of these cases.
6
A clue to the presence
of alloantibodies in the serum of a patient with AIHA is shown
in Table 1. In example A, the strengths of the reactions
Table 1
Antibody Screen Results for Patients With Autoimmune Hemolytic Anemia Without (Example A) or With (Example B) an RBC
Alloantibody Before and After Autoadsorption
*
Example A Example B
I 2+ 0 2+ 0
II 2+ 0 4+ 2+
III 2+ 0 2+ 0
*
Agglutination is read from 0, which is a negative result, to 4+, which is the strongest possible agglutination.
Screening Cell
Unadsorbed Serum
(Autoantibody Only) Adsorbed Serum
Unadsorbed Serum
(Autoantibody Plus
Alloantibody) Adsorbed Serum
Reardon and Marques / TESTING AND TRANSFUSION SUPPORT IN AIHA
S74 Am J Clin Pathol 2006;125(Suppl 1):S71-S77
S74 DOI: 10.1309/ABP0B54GQL74L3KW
American Society for Clinical Pathology
between the patients serum and the 3 screening cells is the
same (2+), and the antibody screen result becomes negative
with the autoadsorbed serum, consistent with the absence of
an alloantibody. In example B, the patients serum reacts
with screening cell II more strongly than with cells I and III,
suggesting that the agglutination results from more than the
autoantibody. Even in the absence of different reactions in
the screen or panel, a laboratory dealing with a specimen
with an autoantibody should proceed with autoadsorption to
ensure that no alloantibodies are being masked by it. Adsorp-
tion is especially important for patients with a history of
pregnancy or transfusion and in patients whose history is
unknown and transfusion is likely.
During autoadsorption, 1 mL of packed autologous RBCs
should be treated first to elute the bound antibody, followed
by incubation with the patients serum at 37C.
4
The purpose
of the incubation is to induce the removal of residual circu-
lating antibody (adsorption) and allow the recognition of the
potential alloantibody.
4
Depending on the strength of the
initial antibody reactivity with the reagent cells (antibody
concentration), multiple adsorptions may be necessary to
completely deplete autoantibody from the plasma. Subse-
quently, the adsorbed serum should be tested again with the
reagent cells to determine the specificity of the alloantibody
in case any reactivity remains. During this step, it is impor-
tant to save adsorbed serum for use when crossmatching. In
rare situations, even 3 adsorptions do not completely remove
the autoantibody from the serum, and crossmatches with
adsorbed serum are still weakly incompatible. Although the
transfusion service should strive to avoid this situation, it
occasionally occurs in patients with severe anemia and
strong autoantibodies. In such patients, the ability to obtain
enough blood to perform repeated adsorptions may be a
limiting factor.
Alloadsorption
Alloadsorption is an alternative to autoadsorption and is
used if patients have received transfusions during the past 90
days or if anemia precludes the availability of enough patient
RBCs for adsorption.
4
In this specialized technique, often
available only in reference laboratories, aliquots of the pa-
tients serum are adsorbed with allogeneic RBCs of known
phenotypes (ie, R
1
R
1
, R
2
R
2
, and rr). Following proper incu-
bations, the various adsorbed serum samples are tested
against panel cells. If one or more aliquots react with sel-
ected reagent cells, an alloantibody can be identified based
on the pattern of reactivity and the knowledge of the antigens
to which each particular aliquot was exposed. If all adsorbed
serum samples fail to react with reagent cells, the presence of
alloantibodies can be ruled out. Because allogeneic adsorp-
tion usually is not available in-house, the turnaround time
may be an issue if transfusion is urgent. However, it remains
a safe alternative to exclude alloantibodies before subsequent
transfusions when autoadsorption is not possible and transfu-
sion is no longer an emergency.
Drug-Induced Hemolytic Anemia
Drugs such as penicillins and cephalosporins and many
others may induce the formation of RBC autoantibodies. It is
important to maintain a high level of suspicion for a drug-
induced phenomenon. In the laboratory, a drug-dependent
autoantibody may be suspected when a patient has a sudden
onset of brisk hemolysis, a positive DAT result, and negative re-
sults for the antibody screen, antibody panel, and autocontrol.
7
This combination of results may be explained by the
role of some drugs in causing AIHA. One of the most com-
mon mechanisms, classically associated with penicillin, is
drug adsorption to the RBC membrane and induction of anti-
bodies to one or more of the following: combination of drug
and membrane components, drug alone, or RBC antigen
alone.
4
To confirm this mechanism, reagent RBCs first need
to be incubated with the potential culprit drug and subse-
quently allowed to react with the patients serum. If aggluti-
nation occurs, the patients physician should be alerted to the
secondary nature of the immune hemolysis and avoid use of
the drug in the future for this patient. If the patient is still
taking the implicated drug, the findings would be indistin-
guishable from primary AIHA. Current drug use would not
require the preincubation step because the implicated drug
would be already present in the patients serum.
Another mechanism for drug-induced AIHA that still is
not completely understood is seen mainly with quinidine and
ceftriaxone. These drugs do not bind well to RBCs but are
thought to induce the formation of drug-antidrug immune
complexes in the patients plasma. Consequently, they lead
to complement activation and intravascular hemolysis even
with small amounts of circulating drug.
The last mechanism of drug-induced hemolytic anemia
is serologically independent of the presence of the drug in
vivo and in vitro. In this case, the RBC autoantibody is
induced initially by drugs such as methyldopa, procaina-
mide, and fludarabine, but the drug is no longer needed for
the antibody to bind.
Thermal Amplitude Test
Although the IgM involved in CAD has higher affinity
for the RBC membrane antigens at 4C, the presence of
hemolysis suggests that it is binding in vivo at physiologic
temperatures. The thermal amplitude test is used to check the
titer of the antibody at various temperatures, which can be
useful for diagnosis and follow-up purposes. For this assay, it
is important that the patients blood sample be kept at 37C
from the point of bedside collection to the separation of the
cells from serum in the laboratory. Serial dilutions of the
Pathology Patterns Reviews
Am J Clin Pathol 2006;125(Suppl 1):S71-S77 S75
DOI: 10.1309/ABP0B54GQL74L3KW S75
American Society for Clinical Pathology
serum then are incubated at 4C, 22C, 30C, and 37C with
both adult and umbilical cord RBCs. The choice of these
reagent RBCs is based on the fact that CAD is due almost
invariably to an autoantibody to the I antigen, which is
present on adult RBCs. Less commonly, the antibody
recognizes the i antigen, a similar but less complex carbohy-
drate antigen found on fetal cells. Cold autoantibodies to
the i antigen are seen classically in patients with infectious
mononucleosis.
In such cases, the antibody and the hemolysis are expec-
ted to be transient. Once all the tubes containing cells and
various dilutions of serum are incubated and agglutination
results recorded, the ability of the patients antibody to bind
at physiologic temperatures (30C and 37C) confirms its
clinical significance. As with the determination of alloanti-
body titers, the CAD IgM titer at each temperature and with
each antigen (I or i) is the last dilution that yields 1+ aggluti-
nation. An example of thermal amplitude test results is given
in Table 2.
Treatment
General Guidelines for Managing Hemolytic Anemia
Clinical management of patients with hemolytic anemia
varies according to the causative disease state. This makes
accurate diagnosis of the utmost importance. No matter
the cause of hemolysis, the erythroid marrow has a limited
capa-city to compensate for the RBC destruction in the
peripheral circulation. In brisk hemolytic crisis, an adequate
supply of substrates needed for hemoglobin synthesis is
essential. Patients who do not have adequate stores of iron
and folic acid will be unable to appropriately increase
marrow production, worsening their anemia. All patients
with hemolytic anemia, especially those with chronic hemol-
ysis, will have increased requirements for folate and need to
be supplemented with oral preparations continuously. Iron
study results need to be monitored, and oral or intravenous
iron therapy should be used if necessary.
Transfusion Support in AIHA
Not all patients with AIHA will require transfusion; the
decision to transfuse must be decided case by case. It may be
more harmful to hold a necessary transfusion than to issue
units incompatible owing to the patients autoantibody.
8
Although crossmatches with autoadsorbed or alloadsorbed
serum may be compatible, it is expected that the autoanti-
body in vivo will cause hemolysis of the transfused cells just
as of the patients own cells. For this reason, such units are
commonly called least incompatible and may be released
from the transfusion service with an official form to be
signed by the patients physician. Such a form documents the
result of the crossmatch, the discussion of the situation with
the patients physician, and the need to monitor the patient
for the risk of hemolysis.
9
Thus, transfusion in AIHA has to
take into account the risk-benefit ratio and must occur in the
setting of close interaction between the clinician and the
transfusion medicine specialist. In an emergency or when
adsorbed serum is not available for crossmatches, the risk of
alloantibodies has to be estimated based on the history of
previous pregnancies or transfusions or the lack of such
predisposing conditions.
Patients with CAD who require a transfusion may re-
ceive compatible units crossmatched at 37C (prewarm tech-
nique) to eliminate interference by the cold antibody.
4
By
prewarming the patients serum sample and a sample from
each RBC unit, it is expected that potential alloantibodies
would still react and be detected during the crossmatch. This
also could be seen if the patients serum sample is incubated
at 37C for 5 to 10 minutes before mixing with previously
warmed reagent panel cells (prewarm panel). If the thermal
amplitude of the IgM agglutinin allows it to react at 37C,
cold autoadsorptions or alloadsorptions may be performed,
although they rarely are needed. An important requirement
for safe transfusion for patients with CAD is the use of a
blood warmer and maintenance of the patients room temper-
ature as close to 37C as possible.
Warm AIHA
Treatment of warm AIHA is targeted at reducing the
amount of antibody being produced or reducing its efficiency
in destroying the RBCs.
10
Corticosteroids generally are the
first line of therapy. These drugs act by blocking the clear-
ance of cells coated with IgG or complement and decrease
the production of new IgG antibody. In several studies it has
been shown that corticosteroids induce remission of antibody
production in approximately 60% to 70% of patients.
11-13
The
typical starting regimen is 1 to 1.5 mg/kg per day of oral pred-
Table 2
Example of Thermal Amplitude Results for a Patient With
Cold Agglutinin Disease
*
Serum Dilution 4C 22C 30C 37C
Undiluted 4+ 3+ 3+ 2+
2 4+ 3+ 2+ 2+
4 3+ 2+ 2+ 1+
8 3+ 2+ 1+ 1+
16 2+ 1+ 1+ 0
32 2+ 1+ 0 0
2+/1+ 0 0 0
1,024 1+ 0 0 0
2,048 0 0 0 0
Titer anti-I 1,024 32 16 8
*
Agglutination is read from 0, which is a negative result, to 4+, which is the
strongest possible agglutination.
Reardon and Marques / TESTING AND TRANSFUSION SUPPORT IN AIHA
S76 Am J Clin Pathol 2006;125(Suppl 1):S71-S77
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American Society for Clinical Pathology
nisone; antibody production usually decreases in 1 to 3 weeks
as determined by a rise in the hemoglobin concentration. The
goal of therapy with corticosteroids should be to induce rem-
ission. After the hemoglobin concentration stabilizes, the corti-
costeroids need to be tapered rapidly. If remission cannot be
maintained, other treatments need to be explored.
Patients unresponsive to corticosteroids or those without
sustained remission are candidates for combined chemo-
therapy and/or splenectomy. Treatment with cytotoxic drugs
(primarily azathioprine or cyclophosphamide) reduces the
production of antibody and raises the hemoglobin concentra-
tion.
11
General indications for their use are lack of response
to or inability to tolerate prednisone or the necessity for a
maintenance prednisone dosage of more than 15 to 20 mg/d
in adults.
11
These drugs may take up to 1 month to produce a
response. Splenectomy shows similar response rates to corti-
costeroids. Approximately 60% of patients will show
improvement of their anemia within 3 weeks of surgery.
14
More recently, there have been case reports showing that
rituximab, a monoclonal antibody to CD20, is effective in
warm AIHA, but the data are preliminary.
15,16
Cold Agglutinin Disease
The simplest, most useful therapy for treating CAD is
avoiding exposure to cold. Patients need to dress warmly,
even in the summer months, including as necessary the use
of stockings, gloves, earmuffs, or scarves. For patients living
in northern climates, CAD may be especially difficult. Little
needs to be done for patients who develop a high-titer cold
agglutinin following an infection with Mycoplasma or the
Epstein-Barr virus because these are transient phenomena.
The severity of the anemia should be followed up and trans-
fusion administered in the acute setting if necessary.
Patients with CAD associated with a lymphoprolifera-
tive disease have a more aggressive course. Corticosteroids
generally do not diminish antibody production in CAD
except in patients with low titers of antibodies with high
thermal amplitude results.
17,18
These patients may respond to
cytotoxic agents such as cyclophosphamide. In the situation
of severe, life-threatening anemia or digital ischemia, plasma-
pheresis can be lifesaving.
19,20
Because the majority of IgM
antibodies are intravascular, plasma exchange can rapidly
lower the antibody titer. However, the effect of plasma
exchange is relatively short-lived because the half-life for
protein regeneration is only 5 days. Thus, plasmapheresis
should be used as a bridge until cytotoxic agents reduce anti-
body production. As in warm AIHA, rituximab was reported
to have response rates of approximately 50% in an uncon-
trolled, prospective study of 27 patients with CAD.
21
Conclusion
The laboratory investigation of AIHA is complex and
involves a variety of assays Table 3 and considerations.
22
The well-informed health care team, composed of clinicians
Table 3
Summary of Assays Used in the Diagnosis and Management of Patients With AIHA
Test Purpose Comments
AIHA, autoimmune hemolytic anemia; DAT, direct antiglobulin test.
DAT or direct Coombs test Determine the presence of IgG and/or
C3 on the RBC surface
Positive in almost 100% of cases of AIHA;
amount of IgG and/or C3 correlates with
risk of hemolysis
Elution Characterize the specificity of the
RBC-bound IgG
If DAT is only weakly positive for IgG, eluate
may not react with panel cells; very
important in patients who have received
transfusions recently
Antibody screen or indirect Coombs test Assess for the presence of autoantibody
and/or alloantibody in the patients serum
May be negative if all autoantibody is
bound to RBCs
Autoadsorption Remove excess autoantibody from
the patients serum and determine the
presence of alloantibody
If patient has received transfusion during
last 90 d, adsorption also may remove
alloantibody
Alloadsorption Remove excess autoantibody from
the patients serum and determine the
presence of alloantibody
Useful for patients who have received
transfusion and patients with severe
anemia from whom an adequate specimen
for autoadsorption cannot be obtained
Drug-induced hemolytic anemia test Induce agglutination of RBCs in the
presence of a potential drug
Highly specialized test; not usually available
in the acute clinical setting
Thermal amplitude test Determine whether cold agglutinin can
bind to RBCs at warm body temperatures
Should be done with adult RBCs (positive for
I) and cord blood RBCs (positive for i)
Pathology Patterns Reviews
Am J Clin Pathol 2006;125(Suppl 1):S71-S77 S77
DOI: 10.1309/ABP0B54GQL74L3KW S77
American Society for Clinical Pathology
and pathologists, must work together to treat such patients
properly and efficiently.
From the Department of Pathology, Division of Laboratory
Medicine, University of Alabama at Birmingham.
Address reprint requests to Dr Marques: Dept of Pathology,
619 19th St S, West Pavilion, P230 J, Birmingham, AL 35249-7331.
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