Wintrobe Anemia on Chronic Disease
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Transcript of Wintrobe Anemia on Chronic Disease
12
Wintrobe's Clinical Hematology, 11th Ed
by John P. Greer (Editor), John Foerster (Editor), John N. Lukens (Editor)
Publisher: Lippincott Williams & Wilkins Publishers; 11th edition (December 2003)
Robert T.
Means, Jr.
Anemias Secondary to Chronic Disease and
Systemic DisordersANEMIA OF CHRONIC DISEASE
The anemia that is often observed in patients with infectious, inflammatory, or neoplastic
diseases that persist for more than 1 or 2 months is called anemia of chronic disease.
The characteristic feature of this syndrome is the occurrence of hypoferremia in the
presence of ample reticuloendothelial iron stores. Anemia of chronic disease is defined by
the presence of this unique combination of findings ( 1 , 2 and 3 ). As so defined, the
syndrome does not include anemias caused by marrow replacement, blood loss, hemolysis,
renal insufficiency, hepatic disease, or endocrinopathy, even when these disorders are
chronic. These other syndromes are discussed in the sections Anemia of Chronic Renal
Insufficiency, Anemia in Cirrhosis and Other Liver Diseases, and Anemias Associated with
Endocrine Disorders.
As the discussion above suggests, the designation anemia of chronic disease is far from
perfect ( 4 ). The most commonly proposed alternative, anemia of inflammation ( 4 ), also
has significant deficiencies, and the more pathophysiologically correct term
cytokine-mediated anemia ( 5 ) is not commonly used. Highly specific descriptive
designations, such as anemia of defective iron reuse ( 6 ), hypoferremic anemia with
reticuloendothelial siderosis, and thesauric hypoferremic anemia ( 7 ), are also rarely used.
Associated Syndromes
Anemia of chronic disease is extremely common and, overall, is probably more common
than any anemia syndrome other than blood loss with consequent iron deficiency. Cash
and Sears evaluated all the anemic individuals admitted to the medical service of a busy
municipal hospital during two 2-month periods in 1985 to 1986 ( 8 ). After patients with
active bleeding, hemolysis, or known hematologic malignancy were excluded, 52% of
anemic patients met laboratory criteria for anemia of chronic disease ( 8 ). The syndrome
is also observed in 27% of outpatients with rheumatoid arthritis ( 9 ) and in 58% of new
admissions to inpatient rheumatology units ( 10 ). Clinical disorders commonly associated
with anemia of chronic disease are listed in Table 47.1. However, it should be remembered
that 40% of patients in the series reported by Cash and Sears lacked one of the
traditional chronic associated disorders ( 8 ). Approximately one-third of this latter group
had renal insufficiency, in which pathophysiologic mechanisms implicated in anemia of
chronic disease are active ( 28 ).
TABLE 47.1. Conditions Associated with Anemia of Chronic Disease
Chronic infections ( 8, 13)
Pulmonary infections: abscesses, emphysema, tuberculosis, pneumonia
Subacute bacterial endocarditis
Pelvic inflammatory disease
Osteomyelitis
Chronic urinary tract infections
Chronic fungal disease
Meningitis
Human immunodeficiency virus
Chronic, noninfectious inflammations
Rheumatoid arthritis ( 14, 15, 16 and 17)
Rheumatic fever ( 18)
Systemic lupus erythematosus ( 19)
Severe trauma ( 20)
Thermal injury ( 21)
Vasculitis
Malignant diseases ( 22, 23, 24 and 25)
Carcinoma
Hodgkin disease
Lymphosarcoma
Leukemia
Multiple myeloma
Miscellaneous
Alcoholic liver disease
Congestive heart failure
Thrombophlebitis
Ischemic heart disease
Idiopathic
Clinical and Laboratory Description
Because this type of anemia occurs in association with so many diseases, the clinical
manifestations necessarily vary widely. Usually, the signs and symptoms of the underlying
disorder overshadow those of the anemia, but on rare occasions, reduction of the
hemoglobin level provides the first evidence of the existence of the primary condition.
This situation may be observed particularly in difficult-to-diagnose clinical syndromes,
such as temporal arteritis ( 29 ).
Anemia
DEVELOPMENT AND SEVERITY
Typically, anemia develops during the first 1 to 2 months of illness and thereafter does not progress ( 2 ). The hematocrit usually is maintained between 0.25 and 0.40 ( 2 , 11 , 30 ), but significantly lower values are observed in 20 to 30% of patients ( 8 , 9 ). The hemoglobin concentration and hematocrit generally provide an accurate reflection of the extent to which the circulating red cell mass is reduced, although in certain cases, expansion of the total blood volume would mean that the reduction in red cell mass is less than the hemoglobin or hematocrit indicates ( 11 ).
This is particularly likely in syndromes associated with increased levels of interleukin
(IL)-6. IL-6 produces a dilutional anemia: Expansion of the plasma volume results in a
reduced hematocrit or hemoglobin concentration without changes in the circulating red
cell mass ( 31 ). A general correlation exists between the degree of anemia and the
severity of the underlying disease ( 2 ). For example, infections accompanied by
pronounced fever, chills, and suppuration are associated with more severe anemia than
those with fewer systemic manifestations ( 32 ). In infected wounds, the degree of anemia
is related to the number of organisms present ( 32 ). Correlation has also been observed
between the severity of the anemia and the activity of rheumatoid arthritis, judged by
fever, severity of joint swelling and inflammation, and the erythrocyte sedimentation rate (
16 , 33 ). In patients with malignant disease, anemia is more severe when metastases are
widespread than when the disease is localized; however, the development of anemia does
not require neoplastic invasion of the bone marrow ( 27 , 34 ). Typically, the percentage of
reticulocytes is normal or reduced ( 2 ), although on rare occasions, it may be slightly
increased ( 32 ).
MORPHOLOGIC FEATURES
The erythrocytes usually are normocytic and normochromic;
however, hypochromia and microcytosis may be observed. In older series, microcytosis
[mean corpuscular volume (MCV)