Page 767 - Hematology_ Basic Principles and Practice ( PDFDrive )

654 Part V Red Blood Cells

30
anemia) was 14%. Most CLL patients with AIHA are men. The TABLE
vast majority of patients have (presumably) polyclonal WAIHAs, but 46.3 Autoimmune Hemolytic Anemia After Infections
in all studies, there is small number of cases with CAIHA (specificity
anti-I), often with IgM paraproteinemia. CAIHA
Infection WAIHA (Specificities)
Autoimmune Hemolytic Anemia in Monoclonal Respiratory tract — — + (DL)/PCH
Gammopathy With Unknown Significance and infections
Lymphoplasmacytic Lymphoma (unspecified)
The clinical picture of primary chronic CAD suggests the pres- Viral infections EBV +/− + (anti-i)
ence of an “idiopathic” CAIHAs, but in fact, most of these patients (specific) CMV + +/− (anti-i)
have a clonal disease with either only clonal IgM (IgM-MGUS) Parvovirus + (often with +/− (DL)
or LPL with IgM paraproteinemia and bone marrow infiltration (B19) PRCA)
(or Waldenström macroglobulinemia). Traditionally, the latter Varicella +/− + (anti-Pr, anti-I,
category would be classified as secondary AIHA. More than 90% anti-DL)
of patients with “CAD” have a monoclonal IgMκ; 7% had IgG Rubella — + (anti-Pr1)
or IgA monoclonal immune globulin with λ chains. The course of Monotypic IgM
CAD is usually indolent. Fewer than half of patients require transfu- HIV + + (anti-I, anti-i,
sions, and the risk for progression to highly malignant lymphomas anti-Pr)
is small.
Bacterial Mycoplasma +/− + (anti-I, anti-Pr)
Autoimmune Hemolytic Anemia in Other infections Brucellosis +/− + (anti-I)
Lymphoproliferative Diseases and Myeloma (specific) Haemophilus + (DL)
The prevalence of AIHA is low in NHL, ranging from 0.23% to influenzae
2.6%. AIHA has been described in all histologic subtypes of NHL. Parasitic Visceral + —
Based on the prevalence of NHL, the association with AIHA is infections leishmaniosis
highest with SMZL, LPL, angioimmunoblastic T-cell lymphoma, (specific)
and γ heavy chain disease. The antibody may be either a warm —, Not reported; +, predominant type of autoimmune hemolytic anemia; +/−,
(two-thirds) or a cold (one-third) antibody. In NHL, there seems to single or few cases reported; CMV, cytomegalovirus; DL, Donath–Landsteiner
be a relatively frequent association of AIHA with LA, C1-esterase antibody; EBV, Epstein-Barr virus; PCH, paroxysmal cold hemoglobinuria;
deficiency, or essential cryoglobulinemia. PRCA, pure red blood cell aplasia.
A number of predominantly WAIHAs have been described in IgG
and IgA myelomas.
Autoimmune Hemolytic Anemia in Myeloid Disorders found after unspecific respiratory infections. In many cases, the
13
Generally, AIHA is rare in patients with myeloid malignancies. A course of AIHA is short, uncomplicated, and self-limited, but some
number of cases have been reported in myelodysplastic syndromes, cases with a severe, even fatal, course, particularly in patients with Pr
particularly chronic myelomonocytic leukemia. Very few cases were antibodies and in Mycoplasma-associated AIHA, have been reported.
described in acute myelogenous and lymphoblastic leukemia, myelo- In AIHA associated with bacterial infections or in leishmaniasis,
fibrosis, and polycythemia. treatment of the infection seemed to be beneficial.
AIHA has been described in a few cases of acute hepatitis A, B,
Autoimmune Hemolytic Anemia in Solid Tumors C, or E, and in a number of cases of untreated chronic hepatitis C.
A special, rare, but highly interesting cause of WAIHA is ovarian However, in a large study, an increased prevalence of AIHA has only
dermoid cyst. These patients respond very poorly to drug therapies, been found in interferon (IFN)-treated hepatitis C patients. 31
but the AIHA resolves completely, and the DAT result becomes Anecdotal reports have described patients in whom WAIHAs were
negative a few weeks after ovariectomy. The same behavior has been associated with measles, Chlamydia pneumoniae, or miliary tubercu-
described in microcystic adenoma of the pancreas and dermoid cyst losis and CAIHAs with adenovirus, measles, leptospiral pneumonia,
of the mesentery associated with AIHA. Escherichia coli infection (all anti-I), pneumococcal pneumonia
AIHA is rarely but definitely associated with solid tumors. It is a (anti-Pr), Haemophilus influenzae (DL), or Bartonella henselae (DAT
very rare complication of lung, renal cell, and ovarian cancer. In some negative).
cases of renal cell cancer, AIHA resolved after curative surgery. Some cases of AIHA have been described after vaccination against
hepatitis B, influenza (MF59 adjuvanted), diphtheria–tetanus–per-
tussis, or rubella. Such associations could not be confirmed in sys-
Infection-Related Autoimmune Hemolytic Anemia tematic studies.

In immunocompetent patients, AIHA may occur after viral, bacterial,
or parasitic infections (Table 46.3). Virus-associated AIHA occurs Drug-Induced Autoimmune Hemolytic Anemia
mostly in newborns and children; bacterial AIHA occurs more often
in adults. The onset of AIHA is often shortly after signs of infection Historically, methyldopa, an antihypertensive drug, was the first
but sometimes after a latency time up to weeks. After some specific known drug to induce AIHA. The prevalence of methyldopa-induced
infections, patients may develop preferentially a warm or a cold AIHA is 1% with 10% to 20% DAT-positive patients without
antibody (sometimes with specific targets such as I, i, P, or Pr antigen), anemia, indicating that DAT positivity is not always followed by
but in almost all instances beside the dominant antibody (cold or overt disease. Currently, IFN-α and purine nucleoside analogues are
warm), there are a few cases of another antibody (see Table 46.3). Of the most common causes of drug-induced AIHA (Table 46.4). The
particular interest is varicella-zoster virus-associated and rubella- diagnosis of drug-induced AIHA in a patient with AIHA after drug
associated CAIHAs, because the cold antibody is mostly directed to exposure can only be made if the indirect DAT result is positive and
the Pr antigen and the AIHA is clinically severe. In Mycoplasma- the RBC eluate contains a RBC antibody. Such tests have not been
associated AIHA, the antibody target is almost always “I”. After performed in all patients in whom drug-induced AIHA was claimed.
Mycoplasma infection, the DAT result is positive in 50% to 60% of The temporal relationship between drug exposure and AIHA is
cases, but anemia is rare. In some specific infections, the antibody complex. In some instances, AIHA may occur after long-term expo-
was a DL antibody, but in a large study, most DL antibodies were sure to a drug (IFN or targeted antibodies). In AIHA caused by