Anemia of Chronic Disease

(Anemia of Inflammation, Iron Reutilization Anemia)

In this factsheet:
The Facts on Anemia of Chronic Disease
Causes of Anemia of Chronic Disease
Symptoms and Complications of Anemia of Chronic Disease
Diagnosing Anemia of Chronic Disease
Treating and Preventing Anemia of Chronic Disease

The Facts on Anemia of Chronic Disease

The blood that circulates throughout the body performs a number of critical
functions. It delivers oxygen, removes carbon dioxide, and carries life-sustaining
nutrients. By acting as the vehicle for long-distance messengers (such as hormones),
blood helps the various parts of the body communicate with each other. This is carried
out by blood cells, working in partnership with the liquid part of the blood (plasma).
Most of the cells that make up your blood are red blood cells (erythrocytes). White
blood cells (leukocytes) - which defend the body against foreign matter such as
bacteria, viruses, and fungi - are also present.
Anemia occurs when there aren't enough healthy red blood cells in the blood.
Most anemias are more of a symptom than a disease and can be the result of a variety
of health conditions. With any form of anemia, it's important to find the cause before
treatment begins.
Anemia of chronic disease develops as a result of a long-term infection or disease.
Usually, it does not cause severe anemia. Anemia of chronic disease is thought to be
the second most common type of anemia, next to iron deficiency anemia. Although
anemia of chronic disease is most often seen in people who have a chronic disease, it
can also appear in young children who only have a simple ear infection. Anemia of
chronic disease may go unnoticed and untreated because the attention is centered on
the disease that is causing it.
In the past, it was believed that anemia of chronic disease was associated only with
infections such as syphilis and tuberculosis. Over the last 30 years, connections
between the condition and diseases such as rheumatoid arthritis, connective tissue
disorders, chronic infection, trauma, or cancer have also been established.

Causes of Anemia of Chronic Disease

Although the exact cause of anemia of chronic disease is not known, it is related
to the effects of chronic diseases on the red blood cells. These conditions cause a
number of changes in the body's red blood cells. The lifespan of red blood cells
becomes shorter, production of new red blood cells in the bone marrow slows down,
and iron is "withheld" so that it cannot be used to make new red blood cells. Normally

the body recycles iron from "old" red blood cells and uses it to make new ones. In
anemia of chronic disease, the body does not recycle iron as easily, so it is "held up"
in the old red blood cells.
The following are examples of conditions that can cause anemia of chronic
disease:

chronic infections (e.g., tuberculosis, lung abscess, and endocarditis)

autoimmune diseases or diseases with inflammation (e.g., rheumatoid arthritis,
lupus, ulcerative colitis, Crohn's disease, giant cell [temporal] arteritis)
cancers (e.g., Hodgkin's disease, lung cancer, breast cancer)

Symptoms and Complications of Anemia of Chronic

Disease
There is generally a chronic illness or infection present that causes anemia of
chronic disease, so the symptoms you may experience will vary. The primary
condition causing the anemia will have its own set of symptoms (such as fever in the
case of infection). Symptoms of the anemia may include pale skin, lack of energy,
fatigue, headache, lethargy (a feeling of "laziness"), shortness of breath during
exercise, and dizziness.
Since anemia of chronic disease is a secondary condition resulting from a primary
disease, its treatment is often overlooked. However, it's essential to diagnose and treat
it because it may weaken the person who has it, making it harder to recover from the
primary disease.

Diagnosing Anemia of Chronic Disease

Anemia of chronic disease isn't usually severe, and symptoms related to the
underlying disease often cover up those of the anemia. This can make it more
difficult to diagnose.
Accurate diagnosis depends on blood test results such as the following:

hemoglobin: low
reticulocyte count: low to normal
serum ferritin level: normal to elevated
serum iron: low
total iron binding capacity (TIBC): low

A low iron serum level (but a normal-to-elevated serum ferritin level) is the most
important and main sign that anemia of chronic disease is present. With
inflammation, the level of certain plasma proteins called acute phase proteins is
higher in the blood. The increase in these proteins usually leads to an increase in the
blood's sedimentation rate, which is determined by a blood test.

A bone marrow biopsy may be performed. When examining the bone marrow, the
most important factor is to measure iron levels. With anemia of chronic disease, iron
stores will be increased in the bone marrow. This helps in making the diagnosis
because an increase in iron stores, combined with low serum iron levels, is found in
anemia of chronic disease.

Treating and Preventing Anemia of Chronic Disease

People with a chronic disease should be carefully monitored for anemia so that it
can be diagnosed and treated.
In most cases, the type of inflammatory disease or tumour that's causing the anemia
determines the treatment for anemia of chronic disease. It is important to find and
treat the underlying cause of the anemia. Once all other causes of anemia are ruled out
and the inflammation, infection, or other problem is identified and treated, the anemia
can be improved.
Medications that are a synthetic form of erythropoietin (e.g., epoetin alfa*,
darbepoetin alfa) stimulate the bone marrow to produce more red blood cells. They
may be recommended if treatment for the underlying condition isn't effective or
possible.
A blood transfusion may be needed if the anemia is severe, and hormone replacement
therapy may be used if the anemia is caused by endocrine failure. When the anemia is
caused by liver disease, treatment to restore liver function usually improves it.
During the treatment of anemia of chronic disease, it's important to consider the
possibility of other contributing factors such as chronic blood loss or non-absorption
of iron, which may cause more severe anemia. People with cancer are often
malnourished and may have an iron deficiency. In these cases, it may or may not be
necessary to take iron supplements.

*All medications have both common (generic) and brand names. The brand name is
what a specific manufacturer calls the product (e.g., Tylenol). The common name is
the medical name for the medication (e.g., acetaminophen). A medication may have
many brand names, but only one common name. This article lists medications by their
common names. For more information on brand names, speak with your doctor or
pharmacist.
CASE REPORT
Year : 2011 | Volume : 3 | Issue : 1 | Page : 89-91 Immune hemolytic anemia in a
patient with tuberculous lymphadenitis
Manjunath Nandennavar, Sanju Cyriac, Krishnakumar, TG Sagar
Department of Medical Oncology, Cancer Institute, Adyar, Chennai, India

Click here for correspondence address and email

Date of Web
Publication

4-Mar2011

Abstract
Anemia in tuberculosis is usually anemia of chronic disease. Severe hemolytic anemia
is exceedingly rare in tuberculosis patients. We report a patient diagnosed with
tubercular lymphadenitis complicated by Coomb's positive hemolytic anemia. Patient
responded well to antituberculous treatment. Hematological parameters improved
after initiation of antituberculosis treatment. To the best of our knowledge, this is the
first case from India of an adult patient with tuberculous lymphadenitis presenting
with Coomb's positive hemolytic anemia.
Keywords: Immune hemolytic anemia, Tuberculous lymphadenitis, Anemia in
tuberculosis
How to cite this article:
Nandennavar M, Cyriac S, Krishnakumar, Sagar TG. Immune hemolytic anemia in a
patient with tuberculous lymphadenitis. J Global Infect Dis 2011;3:89-91
How to cite this URL:
Nandennavar M, Cyriac S, Krishnakumar, Sagar TG. Immune hemolytic anemia in a
patient with tuberculous lymphadenitis. J Global Infect Dis [serial online] 2011
[cited 2012 Feb 2];3:89-91. Available from: http://www.jgid.org/text.asp?
2011/3/1/89/77303

Introduction
Tuberculosis is a common disease in developing countries and has diverse clinical
manifestations. Patients can have various hematological abnormalities, most common
being normocytic normochromic anemia. Other causes include malnutrition,
malabsorption, pyridoxine deficiency, etc. Coomb's positive hemolytic anemia is a
very rare cause of anemia associated with TB and only few case reports have been
published. The case presented here had tuberculosis lymphadenitis associated
Coomb's positive hemolytic anemia which resolved on treatment with anti
tuberculous treatment.
Case Report
A 19-year-old girl presented with swelling in the left side of the neck of 1 year

duration. She also had fatigue and headache. She did not have any history of fever or
night sweats. Physical examination revealed pallor, icterus, and multiple left cervical
lymph nodes. These lymph nodes were firm, nontender, matted, and mobile. Systemic
examination showed mild splenomegaly. Laboratory findings on admission were as
follows: hemoglobin 3.5 g/dL, total WBC count 4800/mm 3 (52% neutrophils and
48% lymphocytes), platelet count 225,000/ mm 3 , MCV 97, MCH 30.5 fL, and
reticulocyte 12%. Peripheral smear showed anisopoikilocytosis with macrocytosis and
spherocytosis. Bone marrow examination showed erythroid hyperplasia. Biochemical
tests were as follows: total bilirubin 3.7 mg/dL, direct bilirubin 2.0 mg/dL, indirect
bilirubin 1.7 mg/dL, LDH - 720 U/L and haptoglobulin 20 mg/dL. Coomb's test done
prior to transfusion was positive ([Table 1] for hematological parameters before
starting anti-tuberculosis therapy). Serum levels of urea, creatinine were within
normal limits and glucose 6 phosphate dehydrogenase activity was normal. Serologic
tests for antinuclear antibodies, human immunodeficiency virus, mycoplasma,
hepatitis B and C virus were negative. Left cervical lymph node biopsy showed
caseating granulomatous lymphadenitis [Figure 1] Mantoux test was positive (18 mm
induration). Chest X-ray was normal and ultrasound of abdomen revealed
splenomegaly.
Table 1: Laboratory parameters of the patient during hospital
stay
Click here to view
Figure 1: Langerhan's giant cells seen in tuberculosis
lymphadenitis
Click here to view

Patient was started on antituberculosis treatment with isoniazid (300 mg qday),

rifampicin (450 mg qday), ethambutol (800 mg qday), and pyrazinamide (750 mg
bid). Her symptoms of fatigue and headache started improving after 2 weeks of
treatment. Hemoglobin improved to 5 gm/dL after 2 weeks of treatment and Coomb's
test became negative after 2 months [Table 2]. She is on follow-up and is in excellent
health.
Table 2: Laboratory parameters of the patient during
antituberculosis treatment
Click here to view

Discussion

Autoimmune hemolytic anemia (AIHA) represents a spectrum of disorders in which

antibodies against self-antigens on the erythrocyte membrane cause a shortened red
blood cell (RBC) life span. AIHA can occur as an idiopathic (primary) disorder or can
coexist with another disease (secondary). AIHA can also occur following
administration of certain drugs (drug induced). The incidence of AIHA is estimated to
be approximately 1 in 100,000 in adults. [1]
Tuberculosis presents with a wide variety of hematological manifestations. The most
common is normocytic normochromic anemia of chronic disease. Anemia in
tuberculosis is most often due to nutritional deficiency, malabsorption syndromes,
failure of iron utilization, and bone marrow suppression. AIHA is exceedingly rare in
tuberculosis.
Siribaddane et al., first reported association of autoimmune hemolytic anemia in
tuberculous lymphadenitis in 1997. [2] A detailed search revealed only 7 cases of
AIHA in tuberculosis in the English literature; 3 of them responded to antituberculous treatment (ATT) alone without need for blood transfusion or steroids. [3],[4]
Mehmet Turgut et al.,from Turkey, reported a case of pulmonary tuberculosis with
AIHA responding to ATT alone without the need for blood transfusion. [3] Ping-Hung
Kuo et al. from Taiwan, reported an episode of Coomb's positive AIHA in a patient
with Miliary tuberculosis resulting in a hemoglobin of 5g/dL. [5] The hematological
parameters in their case improved without the use of steroids or blood transfusion.
Bakshi S et al., from India, reported a case of AIHA in childhood tuberculosis
(mediastinal tuberculous lymphadenitis), which responded to steroids and
antituberculous therapy. [6] Abdullah Abba et al., from Saudi Arabia, reported AIHA in
an Indonesian housemaid suffering from intestinal tuberculosis. In their case, AIHA
responded to ATT alone. [7] Gupta V et al., from India, reported about a child with
abdominal tuberculosis and AIHA, which responded to steroids and ATT. [8]
Apart from autoimmune hemolytic anemia, other autoimmune phenomena like
vasculitis and thrombocytopenia have been associated with tuberculosis. Borie et al.
reported a case series of 5 patients with tuberculosis and thrombocytopenia who were
treated with ATT and other drugs like danazol, vincristine, IV immunoglobulin, and
steroids. [9]
Conclusion

Tuberculosis can cause hemolytic anemia. This case highlights the need for detailed
evaluation of anemia in tuberculosis patients and to consider AIHA in the differential
diagnosis of anemia in these patients. One of the main treatments of AIHA is the
administration of steroids; however, this may be potentially harmful in tuberculosis
patients. This case report is to emphasize the effectiveness of ATT alone to correct
AIHA in tuberculosis patients.
Approaches to Treating Chronic Anemia in Developing Countries: Anemia of
Inflammation

Authors and Disclosures

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Summary and Introduction

Iron Deficiency
Folate Deficiency
Vitamin B
Anemia of Inflammation
Hemoglobinopathies
Practical Approach to Diagnosis Of Chronic Anemia
References
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Anemia of Inflammation
The anemia of inflammation is an acquired condition that is commonly observed in
the clinical settings of infection, arthritis, malignancy, trauma and organ failure.
Initially, the anemia is mild, characterized primarily by a decrease in the number of
red blood cells. Over time, the anemia becomes more severe, with hypochromic,
microcytic erythrocytes.[18] Although the anemia increases the morbidity of the
underlying illness, it probably results from a host-defense mechanism designed to
sequester iron from the invading pathogens.
There are three major processes involved in the pathogenesis of anemia of
inflammation. First, there is a modest (<10%) shortening of red cell survival which
creates a demand for a slight increase in bone marrow red cell production. The bone
marrow cannot respond adequately owing to impaired erythropoiesis and impaired
mobilization of iron from the reticuloendothelial cells.[19] The impairment of
erythropoiesis, in turn, results from two processes: blunting of the expected increment
in erythropoietin production in response to the degree of anemia, and a decreased
response of the erythroid progenitors to erythropoietin. It is reported that the blunting
of bone marrow response to erythropoietin may be mediated by interleukin-1 (IL-1),
tumor necrosis factor a and transforming growth factor , which affect erythropoietin
mRNA transcription.[20] It has also been demonstrated that IL-1, which is increased
during inflammation, inhibits erythroid colony-forming units, which later develop into
erythroblasts.[21]
Two common causes of anemia of inflammation in developing countries are TB and
HIV. Approximately, one-third of the world's population is infected by

Mycobacterium tuberculosis. Ninety-five percent of TB cases and 98% of TB deaths

are in developing countries. In 2000, sub-Saharan Africa had the highest TB incidence
rate of 290/100,000 per year and the highest annual rate of increase of cases (6%).[22]
TB is one of the most common causes of anemia in adult males and non-pregnant
females in developing countries and probably the most common cause of adults
requiring hospital care and in some areas blood transfusion.[23] Apart from the
disease directly causing anemia of inflammation, the various therapeutic agents used
in its management may lead to hematological complications. These include the
sideroblastic anemia of pyridoxine inhibitors, hypoplasia or aplasia of one or more
cell lines, disturbances of folate or vitamin B12 metabolism, and immune hemolysis.
[22]
An estimated 38.6 million people worldwide were living with HIV in 2005. An
estimated 4.1 million became newly infected with HIV and an estimated 2.8 million
lost their lives to AIDS.[24] Anemia is very common among HIV-infected people in
Africa and is an indicator of poor prognosis.[25] Anemia becomes increasingly
frequent as HIV disease progresses; 70-95% of patients with full-blown AIDS are
anemic.[8] The major mechanism is the anemia of inflammation, but other factors
include direct depression of erythropoiesis by HIV, focal or diffuse fibrosis or serous
fatty atrophy of the marrow cavity. Co-infections with parvovirus B19, L. donovani
and other micro-organisms cause severe red cell hypoplasia.[8]
Clinical Management
The clinical manifestations of anemia of inflammation include depressed serum iron
levels in spite of adequate iron stores, decreased total iron binding capacity and
increased ferritin. Often, iron-laden macrophages can be observed in bone marrow
specimens.[26] Intestinal absorption of iron is impaired, which will eventually lead to
true iron deficiency.
Usually, patients will present with mild to moderate anemia; however, for longstanding causes patients present with severe anemia requiring blood transfusion. Iron
therapy is usually not indicated, as iron is present but sequestered in the bone marrow.
Treatment of the primary condition leads to the mobilization of all iron and reversing
of the 'functional' iron deficiency. Therefore, the mainstay of management is to treat
the underlying cause of inflammation.
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Transfusion Alter Transfusion Med. 2008;10(2):75-81. 2008 Blackwell Publishing

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