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    Anemia of Chronic Disease

    Anemia of chronic disease (ACD) or anemia of inflammation refers to the mild or moderately severe form of anemia, usually associated with chronic inflammatory disorders, infections and cancers. The amount of circulating iron in the serum is low, but body stores remains more or less normal.


    Clinical manifestations of ACD depend on the underlying disease that causes the condition. Many patients remain asymptomatic as anemia in itself may not present with any specific symptoms. When present, some of the common symptoms of the disease include pallor, fatigue, lethargy, irritability and loss of stamina. Increased tiredness, tachycardia, and breathlessness are also seen. Some less common symptoms of ACD include decreased tolerance for physical stress, palpitations, disturbed sleep, loss of appetite, myalgia, lightheadedness, and chest discomfort. Decreased cognitive ability, pallor of conjunctiva, orthostatic hypotension and ascites may be noted as physical findings.

    Entire body system
    • Causes of anemia Different types of anemia and their causes include: Iron deficiency anemia.[]
    • Anemia of chronic disease is often confused with iron deficiency anemia.[]
    • Related Diseases Fibromyalgia Osteoporosis Avascular Necrosis Depression APA Syndrome Anemia Anemia of Chronic Disease Anemia of chronic disease is probably the second most common form of anemia, the first being the iron deficiency anemia.[]
    • […] severe to cause anemia.[]
    • Frequently, patients have signs of a disorder that is made worse by the anemia, such as worsening congestive heart failure, cognitive impairment, dizziness and apathy.[]
    Cold Intolerance
    • […] with the following symptoms: Generalized weakness or malaise, easy fatigability Generalized body aches, or myalgias Orthostatic symptoms (eg, lightheadedness, dizziness) Syncope or near-syncope Decreased exercise tolerance Chest discomfort Palpitations Cold[]
    • -hypochromic -disorders of iron metabolism -disorders of globin synthesis -disorders of porphyrin and heme synthesis -severe red cell fragmentation (MCV may be normal or borderline) widening of the central pallor in RBCs Disorders of Iron Metabolism -[]
    • Signs include pallor, lethargy, splenomegaly, and sometimes icterus, bilirubinuria and hemoglobinuria.[]
    • May have mild pallor but will not have signs of circulatory collapse Similar disease can be seen more acutely in the setting of anemia of critical illness (also part of AI).[]
    • In 19th-century Europe, tuberculosis was the major killer, and the pallor associated with this disease was romanticized in the art literature of the time.[]
    • [] Pallor Decreased cognitive ability, pallor of conjunctiva, orthostatic hypotension and ascites may be noted as physical findings.[]
    Refractory Anemia
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  • neurologic
    • When there are symptoms, they vary but may include paleness of the skin, lack of energy, headache, shortness of breath, dizziness, and heart palpitations.[]
    • Symptoms include: Pale complexion, dizziness, fatigue, and rapid heartbeat Infection, fever (even mild) Diagnosis Your doctor will ask about your symptoms and medical history, particularly any history of chronic inflammatory or infectious disease or cancer[]
    • Because the lack of healthy red blood cells prevents proper delivery of oxygen to the body's tissues and organs, a person who has this type of anemia may be pale, listless, weak, and dizzy and have a fast heartbeat.[]
    • 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.[]
    • Symptoms of anemia can include shortness of breath, fatigue, weakness, dizziness, feeling cold all the time, a rapid pulse, heart palpitations, and headache.[]
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  • cardiovascular
    • Clinically it is manifested by weakness, exercise intolerance, hyperpnea which is only moderate, pallor of mucosae, tachycardia and a large increase in the intensity of the heart sounds.[]
    • The presentation may include the new onset or increased tiredness, pallor, breathlessness and tachycardia.[]
    • Mild pallor Mild tachycardia, may be inapparent at rest Very rarely more overt signs of anemia such as flow murmur, gallop, or hepatomegaly Physical findings of the underlying disease Diagnostic Tests & Interpretation If only the serum iron is obtained[]
    • There are no characteristic clinical findings of this type of anemia except for nonspecific alterations (cutaneous mucosa paleness, tachycardia).[]
    • Increased tiredness , tachycardia , and breathlessness are also seen. []
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  • Eyes
    Conjunctival Pallor
    • The relation of conjunctival pallor to the presence of anemia.[]
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  • Workup

    Before confirming on ACD, other diseases that present with normochromic and normocytic anemia should be excluded. Conditions of liver and endocrine system also should be evaluated. Differential diagnosis would include aplastic anemia, myeloid metaplasia, liver cirrhosis, hyperthyroidism, hypoadrenalism, hypothyroidism and, primary and secondary hyperparathyroidism.

    Laboratory tests are important in the evaluation of ACD. Tests that are of confirmatory value include RBC count, peripheral blood smear, reticulocyte count, and bone marrow biopsy. For differential diagnosis, serum levels of vitamin B12 and folic acid, serum bilirubin, heavy metals, iron panel and TSH would be of help. Patients with ACD may have adequate levels of reticulocyte in the serum, but with serum iron, total iron-binding capacity and transferrin may remain low. Measuring serum levels of ferritin helps in diagnosis as it is directly related to stores of iron. About 1µg/L of ferritin in serum corresponds to approximately 8 mg of stored iron. ACD is often characterized by increased levels of ferritin associated with immune activation seen in inflammatory diseases. ESR is elevated in most of the cases of ACD.

    RBCs may be normochromic and normocytic, but in some cases hypochromic and microcytic. This is particularly noticed in case of Crohn disease and rheumatoid arthritis. Soluble transferrin receptor levels are also indicative of ACD as this is a mark of iron stores in the bone marrow. This helps to differentiate ACD from iron deficiency anemia [8].


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  • Laboratory

    Erythrocytes Decreased
    • Its etiology is multifactorial and involves practically all steps of erythrocyte function, i.e. there is a deficient erythropoiesis an erythrocyte decreased survival and increased hemolysis and blood loss.[]
    Ferritin Increased
    • Disordered iron metabolism as manifested by a low serum iron, decreased serum transferrin, decreased transferrin saturation, increased serum ferritin, increased reticuloendothelial iron stores, increased erythrocyte-free protoporphyrin, and reduced iron[]
    • […] with microcytosis Decreased plasma iron Decreased iron-binding capacity Normal or slightly low transferrin saturation Decreased marrow sideroblasts Normal or elevated reticuloendothelial iron Elevated free erythrocyte protoporphyrin Normal or elevated ferritin[]
    Free Erythrocyte Protoporphyrin
    • free erythrocyte protoporphyrin Decreased serum ferritin Decreased hepcidin In both iron deficiency and anemia of chronic disease: Decreased plasma iron Decreased transferrin saturation Decreased marrow sideroblasts Elevated free erythrocyte protoporphyrin[]
    • Serum Hb: normocytic, normochromic, mean 60-90 g/L normal or decreased reticulocytes decreased serum iron and TIBC (elevated transferrin) increased free erythrocyte protoporphyrin (FEP) increased copper, WBC, ESR 2.[]
    • Free erythrocyte protoporphyrin levels may serve as an ancillary test in patients with ACD.[]
    Hemoglobin Decreased
    • Anemia of chronic disease (ACD) occurs when, as a feature of persistent conditions like infectious or inflammatory disease and cancer, red cell production and hemoglobin decrease despite adequate iron stores.[]
    • decreasing their inflammatory state, and improving their quality of life [ 9 ].[]
    Iron Decreased
    • Disordered iron metabolism as manifested by a low serum iron, decreased serum transferrin, decreased transferrin saturation, increased serum ferritin, increased reticuloendothelial iron stores, increased erythrocyte-free protoporphyrin, and reduced iron[]
    • Serum Iron : decreased TIBC: decreased [because this is inverse of ferritin] ferritin [stored] : INCREASE transferring saturation: decrease Free erythrocyte protoporphoryin : INCREASE okay ill explain each in simple ways now: 1: step of iron absorption[]
    • In anemia of chronic disease: Mild to moderate anemia Mild anisocytosis Usually normochromic, normocytic but can be hypochromic with microcytosis Decreased plasma iron Decreased iron-binding capacity Normal or slightly low transferrin saturation Decreased[]
    • But, when the bodies iron storage are running high or when there is excessive amount of iron in the body, the liver increases it's hepcidin production and it does this because the hepcidin then turns around and it decreases serum iron, decreases serum[]
    • ACD shows a normal or decreased serum iron, decreased TIBC, transferring saturation greater than 10%, and increased serum transferrin.[]
    Normocytic Normochromic Anemia
    • Anemia of aging 3 is diagnosed in the elderly when a normocytic normochromic anemia with low iron and preserved iron stores develops without an identified underlying disease.[]
    • The most characteristic blood picture is a normocytic normochromic anemia and not iron deficiency, although it may have iron deficiency and even breakdown of red blood cells called hemolysis [ 2 ].[]
    • ACD is a normocytic, normochromic anemia and falls under the category of anemia due to decreased red blood cell (RBC) production.[]
    • Mice contract a normocytic, normochromic anemia after cecal ligation and puncture (CLP) accompanied by lowered serum iron levels.[]
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  • Treatment

    Treating the underlying disease or disorder is the initial therapy step to improve the symptoms. Care should be taken to treat confounding factors like concomitant blood loss, deficiencies of iron, vitamin B12, and folic acid. In most of the cases, degree of anemia is mild and may not require any specific treatment. In case of iron deficiency, steps should be taken to replenish the element.

    In some rare cases, ACD may be severe and exacerbate the underlying cardiac and pulmonary disease. In cases of manifestations of cardiac ischemia, erythrocyte transfusion helps to resolve hypoxia and improve symptoms of ischemia. If symptoms cannot be resolved without complete treatment of the underlying disease, erythropoietin with or without iron is recommended.

    In chronic cases of ACD, agents that stimulate erythropoiesis including epoetin alpha and darbepoetin alpha are suggested. As these proteins have a greater serum half-life, Hb levels can be maintained effectively for a longer duration [9]. Erythropoiesis-stimulating agents are given in case of rheumatoid arthritis, heart failure and malignancy [10]. Patients with chronic kidney failure, cancer patients undergoing chemotherapy, and those with HIV infections should be treated to improve the Hb level to more than 12 g/dl. In acute cases of ACD with severe form of anemia with Hb level lesser than 8.0 g/dl, blood transfusion is the recommended modality. This is particularly important if bleeding is continuous. Transfusion also helps to improve condition in patients with myocardial infarction.


    Prognosis of ACD often depends on underlying cause of the disease. Severity of symptoms and the sudden onset of the condition may also play an important role in the outcome. Some other factors that my influence the prognosis of ACD are age of the patient and presence of comorbid conditions.


    • Decreased cognitive ability, pallor of conjunctiva, orthostatic hypotension and ascites may be noted as physical findings.[]
    • Palpitations Cold intolerance Sleep disturbances Inability to concentrate Loss of appetite The following physical findings may be noted: Skin - Pallor Neurovascular - Decreased cognitive ability Eyes - Pale conjunctivae Cardiovascular - Orthostatic hypotension[]
    • A sudden loss of more than one third of a patient's blood volume, for example, usually results in hypotension, respiratory distress, and acute mental status change, even in a young, previously healthy patient.[]
    Microcytic Anemia
    • Give EPO, esp for cancer pts Sideroblastic anemia -size of RBCs -mech -microcytic anemia -low protoporphyrin means low production of heme, therefore low Hb, therefore microcytic anemia.[]
    • A CBC demonstrates a microcytic anemia.[]
    • Video transcript - [Voiceover] So anemia of chronic disease is the second most common cause of anemia in hospitalized patients and it's a type of microcytic anemia, microcytic anemia.[]
    • The erythrocytes are usually normocytic and normochromic but can be mildly hypochromic and microcytic.[]
    • Called also fragmentation anemia. microcytic anemia anemia characterized by decrease in size of the erythrocytes. myelopathic anemia, myelophthisic anemia anemia due to destruction or crowding out of hematopoietic tissues by space-occupying lesions, neoplasms[]
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  • Etiology

    Etiology of ACD is multifactorial and is marked by low levels of iron in the serum. Iron stores are found to be normal or slightly elevated. ACD is a normocytic, normochromic anemia and falls under the category of anemia due to decreased red blood cell (RBC) production. Reduced response to erythropoietin and diversion of iron from serum to storage also are suspected to be responsible for anemia. Shortening of half-life of RBC’s may add to be another etiologic factor for the development of this condition. Diseases like rheumatoid arthritis, diabetes mellitus, heart disease and trauma are all conditions associated with decreased iron availability, erythropoietin levels and decreased life span of RBCs and hence may lead to ACD [4].

    One of the recent studies report that hepcidin, an antimicrobial peptide secreted by liver, is one of the important factors in regulating serum iron levels. This endogenous peptide is considered to be involved in controlling absorption of iron in the intestine, release of iron from macrophages and transfer of iron from the stores. Inflammatory diseases increase the levels of hepcidin, which in turn brings alteration in iron metabolism through reduced absorption and storing of the element in macrophages, leading to hypoferremia [5].
    Some another causative factors of ACD are interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF-alpha) [6]. These cytokines are known to destroy precursors of RBCs and decrease the levels of erythropoietin receptors [7]. IL-6 induces the production of hepcidin.


    Males have a 30% increased risk of developing ACD when compared to females. Prevalence of the condition ranges from 8% to 44% in elderly patients. Prevalence of ACD is greater in people above the age group of 85 years. About one third of patients with anemia has ACD. Among the general population, it is found in 11% of men while 10.2% of women are affected by this condition, particularly in the age group of 66 to 85 years. About 52% of the patients with anemia, but without iron deficiency, filled the criteria of ACD.

    The most common risk factors for developing ACD include chronic inflammatory conditions like auto immune disorders, neoplasia, chronic kidney disease, acute or chronic infections, and chronic rejection after organ transplantation. Alcoholic liver disease, congestive heart failure, thrombosis, chronic pulmonary disease, diabetes mellitus, and other medical conditions also may precipitate ACD.

    Sex distribution
    Age distribution


    Alteration in the homeostasis of iron, proliferation of erythropoietin precursors, and reduction in life span of RBCs all play an important role in the development of ACD. As the infection or inflammation sets in, concentration of iron in the serum falls as a defensive mechanism to prevent proliferation of microbes. This reduction is brought about by the action of interleukins through production of the micropeptide hepcidin. The peptide binds to the iron efflux channel causing a considerable reduction in the efflux of iron. Increased use of iron from the serum reduces the extracellular pool of the element. This indirectly reduces the amount of iron reaching the site of heme synthesis.

    Increased production of hepcidin by the cytokines affects absorption of dietary iron in the intestine. The demand of iron is high during infection and inflammation and this remains a long-lasting situation. Hepcidin affects the release of iron from the storage affecting the homeostasis of iron in the serum. Cytokines are also known to affect erythroid progenitors, reducing erythropoiesis. Inflammation increases removal of senescent RBCs through activation of macrophages. This causes a slight change in the life span of RBCs, adding to iron deficiency.


    Patients with chronic diseases and cancer should monitor Hb levels to ensure that anemia does not set in.


    Anemia of chronic disease (ACD) or anemia of inflammation is the hypoproliferative anemia associated with chronic or acute immune activation [1]. After iron deficiency anemia, this is the second most common form of anemia. This condition was earlier thought to be associated with inflammation, infections and malignancies. Studies show that the clinical scope of anemia of chronic disease can now be expanded to include many other syndromes in which cytokines launch an inflammatory or immune response [2]. As the number of patients with chronic inflammatory conditions increase, the prevalence of this condition is expected to increase. ACD presents itself as a mild or moderately severe condition, and is characterized by slightly increased levels of erythropoietin and reduced amount of reticulocytes. Levels of leukocytes and platelets depend on the underlying disease that causes anemia. The most characteristic feature is the increase of non-heme iron storage [3].

    Patient Information

    Anemia of chronic disease (ACD) or anemia of inflammation refers to the mild or moderately severe form of anemia usually associated with chronic inflammatory disorders, infections and cancers. The amount of circulating iron in the serum is low but body stores remain more or less normal. This condition is more prevalent among men above the age of 85 years. ACD forms the second most common form of anemia, next only to iron deficiency anemia. About one third of the patients with anemia fall in this category. A number of risk factors increase the chance of developing ACD. This includes autoimmune disorders like rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus. Cancer, kidney disease and infections also are associated with increased risk of ACD.

    Patients may not present any specific symptoms of ACD. In general, fatigue, pale skin, muscle pain and breathlessness are the most common symptoms of this form of anemia. A number of factors result in ACD. This includes:

    • Increased uptake of iron into the cells
    • Inadequate transfer of iron from the body stores
    • Reduced life span of red blood cells
    • Reduced production of red blood cells

    A detailed history and physical examination are needed to check for the presence of this condition. Lab tests including RBC count, blood smear, level of iron and sometimes bone marrow biopsy are suggested for diagnosis of ACD. Hemoglobin levels of these patients normally fall in the range of 8 to 9 g/dl. Levels of iron in the serum will be lower than normal.

    Treatment of the underlying condition is the first step in any modality. For those with very mild symptoms of anemia may not require any specific treatment. In chronic cases of ACD, agents that help to improve production of red blood cells are used in the treatment. Treatment aims to increase hemoglobin levels to more than 12 g/dl, particularly in patients who are undergoing chemotherapy, patients with chronic kidney disease and those infected with HIV. If symptoms of anemia are severe with Hb level falling lower than 8 g/dl, blood transfusion is suggested. If the condition is complicated with ongoing bleeding, blood transfusion helps to maintain the Hb level in normal range. Although ACD is a part of many other diseases, monitoring the Hb levels, particularly in patients with chronic kidney disease, cancer and inflammatory disorders, help to prevent anemia.


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    1. Cash JM, Sears DA. The anemia of chronic disease: spectrum of associated diseases in a series of unselected hospitalized patients. Am J Med. 1989;87(6):638.
    2. Means RT Jr. Recent developments in the anemia of chronic disease. Curr Hematol Rep. 2003;2(2):116.
    3. Baynes RD, Flax H, Bothwell TH, et al. Haematological and iron-related measurements in active pulmonary tuberculosis. Scand J Haematol. 1986;36:280-287. 
    4. Besarab A, Levin A. Defining a renal anemia management period. Am J Kidney Dis. 2000;36(6 suppl 3):S13-23.
    5. Roy CN, Mak HH, Akpan I, et al. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood. 1 2007;109(9):4038-44.
    6. Raj DS; Role of Interleukin-6 in the Anemia of Chronic Disease. Semin Arthritis Rheum. 2009;38(5):382-388.
    7. Taniguchi S, Dai CH, Price JO, Krantz SB. Interferon gamma downregulates stem cell factor and erythropoietin receptors but not insulin-like growth factor-I receptors in human erythroid colony-forming cells. Blood. 15 1997;90(6):2244-52.
    8. Koulaouzidis A, Said E, Cottier R, et al. Soluble transferrin receptors and iron deficiency, a step beyond ferritin. A systematic review. J Gastrointestin Liver Dis. 2009;18(3):345-52.
    9. Macdougall IC; Novel erythropoiesis-stimulating agents: a new era in anemia management. Clin J Am Soc Nephrol. 2008;3(1):200-7.
    10. Scrijvers D, Roila F. Erythropoiesis-stimulating agents in cancer patients: ESMO recommendations for Ann Oncol. 2009;20 Suppl 4:159-61.

    • 2002 E. Mead Johnson Award for research in pediatrics lecture: the molecular biology of the anemia of chronic disease: a hypothesis - CN Roy, DA Weinstein, NC Andrews - Pediatric research, 2003 -
    • Cryopathies: A Review: Classification; Diagnostic and Therapeutic Considerations - SE RITZMANN, WC LEVIN - Archives of internal medicine, 1961 - Am Med Assoc
    • Anemia and red cell distribution width at the 12-month well-baby examination - YS Choi, T Reid - SOUTHERN MEDICAL JOURNAL-BIRMINGHAM , 1998 -
    • Anaemia in low-income and middle-income countries - Y Balarajan, U Ramakrishnan, E Özaltin, AH Shankar - The Lancet, 2012 - Elsevier
    • Anaemia of chronic disease: diagnostic significance of erythrocyte and serological parameters in iron deficient rheumatoid arthritis patients. - G Vreugdenhil, CA Baltus, HG Van Eijk - British journal of , 1990 -
    • Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well - BD Westenbrink, FW Visser, AA Voors - European heart , 2007 - Eur Soc Cardiology
    • Anaemia and micronutrient deficiencies Reducing maternal death and disability during pregnancy - N Van Den Broek - British medical bulletin, 2003 - British Council
    • An index of syndromes and their anaesthetic implications - AEP Jones, DA Pelton - Canadian Journal of Anesthesia/Journal canadien , 1976 - Springer
    • Anemia and decline in physical performance among older persons - BWJH Penninx, JM Guralnik, G Onder - American Journal of , 2003 -
    • 11.4 Dizziness - I Nazareth - Oxford Textbook of Primary Medical Care: Clinical , 2004 -
    • A noncategorical approach to chronic childhood illness. - RE Stein, DJ Jessop - Public health reports, 1982 -
    • A simple test of cardiac function based upon the heart rate changes induced by the Valsalva maneuver - AB Levin - The American journal of cardiology, 1966 - Elsevier
    • Anemia of chronic disease - G Weiss, LT Goodnough - New England Journal of Medicine, 2005 - Mass Medical Soc
    • Clinical study of the efficiency of Poetam in the treatment of the anemic syndrome in pubertal uterine hemorrhages - LS Sotnikova, EV Abramova, NM Shevtsova - Bulletin of experimental , 2006 - Springer
    • Anaemia in low-income and middle-income countries - Y Balarajan, U Ramakrishnan, E Özaltin, AH Shankar - The Lancet, 2012 - Elsevier
    • Trial comparing the efficacy and safety of darbepoetin alfa administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia - L Bastit, A Vandebroek, S Altintas - Journal of Clinical , 2008 -
    • A clinical evaluation of serum ferritin as an index of iron stores - DA Lipschitz, JD Cook, CA Finch - New England Journal of , 1974 - Mass Medical Soc
    • " My Heart's Pounding and Skipping": Evaluation and Management of Palpitations in the Emergency Department - CD Harrison -
    • Annotation: The anaemia of chronic disorders - GE Cartwright, GR Lee - British journal of haematology, 2008 - Wiley Online Library
    • A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation - R Mehran, ED Aymong, E Nikolsky - Journal of the , 2004 - Am Coll Cardio Found
    • Advances in the anemia of chronic disease. - RT Means Jr - International journal of hematology, 1999 -
    • Anemia, chronic renal disease and congestive heart failure—the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists - DS Silverberg, D Wexler, A Iaina, S Steinbruch - urology and nephrology, 2006 - Springer