Page 765 - Hematology_ Basic Principles and Practice ( PDFDrive )

652 Part V Red Blood Cells

The DAT result is positive in 1 in 10,000 to 3 in 10,000 normal Other tests, including blood glucose, Hba 1c , renal and hepatic
persons and 10% of hospital patients without anemia or signs of function tests, HIV serology, hepatitis B antigen, and exclusion of
hemolysis. 23a latent tuberculosis are necessary to avoid complications of steroids (in
WAIHAs) or rituximab (in CAIHAs and WAIHAs).
Step 3: Warm or Cold Autoimmune Hemolytic Anemia?
IMMUNOLOGIC PHENOMENA ASSOCIATED WITH
In a further step, the DAT is carried out with monospecific antibodies AUTOIMMUNE HEMOLYTIC ANEMIA
to IgG and complement (C3d) to find out whether a warm or cold
antibody is the cause of hemolysis. If the DAT result is positive Evans syndrome is the combination of WAIHAs with autoimmune
with IgG alone or with IgG plus C3d, the AIHA is most probably a thrombocytopenia (ITP), a typical but rare association. Platelet
WAIHA. If the DAT result is positive with only C3d, the AIHA is antibodies are usually directed against glycoprotein IIB/IIIA. Neutro-
most probably a CAIHA. The differentiation between WAIHAs and penia occurs in 25% of patients. There is no sex predilection; about
CAIHAs is extremely important for the choice of treatment. half of the cases are secondary. Evans syndrome is relatively more
There are some special diagnostic problems in CAIHAs. If common in patients with SLE, antiphospholipid antibodies (APAs),
26
CAIHAs are suspected, it must be taken care that the blood that is and autoimmune lymphoproliferative syndrome (ALPS). A search
sent to the laboratory is kept at 37°C to get reliable results. Patients for an ALPS is mandatory in younger patients with Evans syndrome.
with only RBC C3d may (rarely) have WAIHAs when the amount In roughly 50% of the cases, AIHA and ITP occur simultaneously;
of RBC IgG is very small. In patients with C3d positivity, the cold in 25%, the disease starts with ITP; and in 16%, the disease starts
agglutinin titer should be determined. If it is greater than 1:512, with AIHA. There may be an interval of several years between the
the diagnosis of a CAD is established. There is no threshold titer onset of AIHA and ITP. 10
that separates normal from abnormal. If the titer is less than 1:512, WAIHA, CAIHA, or a positive DAT result without anemia may
the thermal amplitude of the antibody must be determined. If the be associated with PRCA. PRCA may be either immune mediated
thermal amplitude is above 22°C, the diagnosis is CAD. Mixed such as in T-cell neoplasms (particularly T-cell large granulocytic
type AIHA is rare. The criteria are a positive IgG DAT result and a leukemia) or may be caused by an infection with parvovirus. Patients
positive eluate (WAIHAs) result plus a C3d-positive DAT result and with parvovirus-associated AIHA often present with PRCA.
the presence of CAIHAs with a thermal amplitude of greater than AIHA is definitely associated with APAs and LA. In one single-
30°C (CAIHAs). Many published cases of mixed type antibodies do center prospective study, LA was found in 30% predominantly idio-
not fulfill these criteria. 24 pathic AIHA. AIHA (4%) and Evans syndrome (10%) are frequent
in patients with APAs. It is well established that patients with AIHA
Step 4: Primary or Secondary Autoimmune have a significantly (2.8-fold to 3.8-fold) elevated risk of venous
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thromboembolism. It is likely but not proven that patients with
Hemolytic Anemia? AIHA associated with LA are at a higher risk.
In lymphomas, some cases of AIHA are associated with C1-esterase
In the last diagnostic step, it must be determined whether the AIHA inhibitor deficiency and mixed cryoglobulinemia.
is primary or a complication of an underlying disease (secondary).
The decision regarding which diagnostic procedures should be used
for this purpose depends mainly on the type of AIHA (WAIHAs or SECONDARY AUTOIMMUNE HEMOLYTIC ANEMIA
CAIHAs) and should include history, physical examination, labora-
tory tests, and imaging procedures if indicated. In children and About half of cases of AIHA (or probably even more) are second-
younger patients with WAIHA, evidence for an infection should be ary. The main causes are immune diseases and malignancies. Other
sought. A list of all recent medication should be made. A history of underlying conditions are infections, drugs, transplantation, and
weight loss, fever, or poor general condition and arthritis points to a congenital defects.
malignancy or immune disease as the underlying condition. Palpable
lymphadenopathy and splenomegaly do not belong to the clinical
picture of primary WAIHA. In this case, lymphoma (particularly Temporal Relationship of Secondary Autoimmune
splenic marginal zone lymphoma [SMZL]) should be suspected. Hemolytic Anemia to the Underlying Condition
Laboratory tests should include acute-phase proteins, LDH, quantita-
tive determination of immunoglobulins, and other tests guided by the The temporal relationship of AIHA to an underlying condition
clinical history. A bone marrow examination is not obligatory except is complex. AIHA antedates the diagnosis of malignancy in many
when lymphoma is suspected. Abdominal ultrasonography is reason- cases—in NHL, sometimes for years. In population-based studies,
able in all cases to exclude splenomegaly, the remote (but important) clonal B cells have been detected in some patients with seemingly
possibility of an ovarian teratoma (in women), lymphadenopathy, idiopathic AIHA. In most instances, AIHA occurs concurrently with
or solitary extranodal lymphomas. Some experts recommend CT of the malignancy. In some other cases, AIHA occurred only at the
the abdomen or thorax in all cases, but there is concern of radiation recurrence and rarely in complete remission (CR) after successful
exposure. An activated partial thromboplastin time with a lupus- treatment. In CLL, AIHA occurs in a late phase of the disease. The
sensitive reagent may reveal a LA. Fluorescence-activated cell sorting patients have poor prognostic factors and often have been treated
or PCR for the detection of monoclonal lymphocytes may be done, with various agents.
but the clinical usefulness of such tests to guide treatment decisions In immune diseases, particularly SLE, AIHA is a complication of
is uncertain. the early phase of the disease. Infection-related AIHA occurs shortly
In CAIHA, a history of a febrile illness should prompt a thoracic after the onset of symptoms except in HIV infection, in which AIHA
radiography, and if results are positive, a serologic test for mycoplasma is a complication in the late advanced stage of the disease.
pneumoniae is required. The quantitative determination of serum
Igs and a search for a clonal immunoglobulin by immune fixation
are important. If immune fixation findings are positive, a search for Serologic Type of Autoimmune Hemolytic Anemia in
lymphoma is necessary, which may include bone marrow biopsy Secondary Autoimmune Hemolytic Anemia
even when there is no lymphadenopathy. In addition to classical
CAD, cold agglutinins occurring in association with other cancers, It is an interesting phenomenon that in underlying diseases associated
aggressive lymphomas, or infection should be termed cold agglutinin with AIHA, all serologic types of AIHA may occur, but usually
syndrome. 25 one serologic type (WAIHA, CAIHA, or DL antibody) prevails.