eMedicine Specialties > Emergency Medicine > Hematology & Oncology

Anemia, Chronic

Author: Fredrick Melik Abrahamian, DO, FACEP, Associate Professor of Medicine, University of California at Los Angeles School of Medicine; Director of Education for Emergency Medicine Residency Program, Consulting Staff, Department of Emergency Medicine, Olive View-University of California at Los Angeles Medical Center
Coauthor(s): Eric Wilke, MD, Medical Director, Traditions Emergency Medicine, College Station Medical Center
Contributor Information and Disclosures

Updated: Jan 14, 2008

Introduction

Background

Anemia is defined as an absolute reduction in the quantity of the oxygen-carrying pigment hemoglobin (Hgb) in the circulating blood. Anemia is further broadly subcategorized into acute and chronic. Viewing anemia as a symptom of a disease manifested by low Hgb rather than as an isolated diagnosis is often helpful.

Pathophysiology

Anemia usually is grouped into 3 etiologic categories: decreased red blood cell (RBC) production, increased RBC destruction, and blood loss.

A disease may lead to anemia through a combination of several mechanisms. For example, a GI malignancy may manifest blood loss as well as anemia of chronic disease.

Frequency

United States

Incidence of anemia mirrors the incidence of the underlying cause. Some published studies report the incidence of anemia at 2-15% in the United States and Great Britain.

International

Anemia is far more common in underdeveloped countries than in the United States. The true incidence of anemia is difficult to define because of multiple factors (eg, patient population, geographic location, normal range reference, ability to adequately screen for the disease).

Mortality/Morbidity

Morbidity and mortality are dependent on several variables (eg, underlying disease process, comorbid conditions, chronicity of the disease, patient's diet, patient's access to medical care).

Race

• African Americans have a higher incidence of sickle cell anemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. G-6-PD is essential for RBC protection from oxidative insults and for approximately 10% of RBC energy production.
• Mediterranean populations show a higher incidence of beta thalassemia.

Sex

Sex distribution varies based on the underlying cause. Overall, females have approximately twice the incidence of males of anemia.

Age

Anemia is prevalent in all age groups. Some younger patients may have a better ability to compensate for anemia, which may delay initial diagnosis.

Clinical

History

A comprehensive history and physical examination is vital in determining the cause of anemia. For example, a family history of a dominant inheritance pattern would suggest spherocytosis. In addition, knowing what medications the patient is taking is vital, as many drugs and toxins can cause anemia (eg, alcohol, isoniazid, lead). The spectrum of symptoms manifested by anemia is dependent on many factors, including underlying medical condition, medications, rate of onset, and the individual's ability to compensate for the deficit. The hallmark of chronic anemia is the ability of patients to sustain a relatively normal level of function at significantly lower than normal Hgb levels.

• Primary symptoms result from tissue hypoxia and might include the following:
  • Fatigue, weakness, irritability
  • Headache
  • Dizziness, especially postural
  • Vertigo
  • Tinnitus
  • Syncope
  • Dyspnea, especially with increased physical activity (exercise intolerance)
  • Chest pain, palpitations
  • Difficulty sleeping or concentrating
  • Thirst
  • Anorexia
  • Decreased urine output/bowel irregularity
  • Decreased libido or impotence
• Anemia is a manifestation of an underlying disease process and is not a diagnosis in itself. A wide array of diseases, including inflammations, infections, and malignancies, may at some point be associated with anemia. Common conditions associated with anemia include the following:
  • Gastritis
  • Gastric or duodenal ulcer
  • Liver or renal disease
  • Hypothyroidism
  • Sickle cell disease
  • Hypermenorrhea
  • Previous history of anemia or blood transfusions
  • Thrombocytopenia or blood coagulation disorders
  • Cancer or other chronic illness (eg, rheumatic disease)
  • Poor diet, especially iron deficiency

Physical

Physical findings mirror the underlying disease process and the duration from the onset. Patients with chronic anemia usually do not manifest typical physical findings associated with acute anemia. Potential physical findings include the following:

• Skin pallor
  • The usefulness of this sign is limited by the color of the skin, Hgb concentration, and the fluctuation of blood flow to the skin.
  • The color of the palmar creases is a better indicator. If they are as pale as the surrounding skin, Hgb is usually less than 7 g/dL. Patients also may exhibit purpura, petechiae, and jaundice.
• Eyes
  • Pale conjunctiva
  • Retinal hemorrhages
• Cardiovascular
  • Tachycardia
  • Orthostatic hypotension
• Pulmonary
  • Tachypnea
  • Rales
• Abdomen
  • Hepatomegaly and/or splenomegaly
  • Ascites
  • Masses
  • Positive result on Hemoccult test
• Neurologic
  • Peripheral neuritis/neuropathy
  • Mental status changes

Causes

The first question a clinician must address is whether the anemia is due to a decreased production of RBCs or to increased destruction or loss of RBCs. The reticulocyte count is the most valuable test in answering this question. If the reticulocyte count is low, a failure in RBC production is indicated. If it is high, hemolysis is suggested.

• Hypochromic microcytic anemia
  • Possible causes include iron deficiency, thalassemia, sideroblasts, and lead poisoning.
  • Anemia of chronic disease commonly is manifested by normocytic normochromic indices; however, microcytic hypochromic indices also can be associated with anemia of chronic disease.
• Macrocytic anemia: Possible causes include vitamin B-12 deficiency, folate deficiency, liver disease, and hypothyroidism.
• Normocytic anemia is further divided into 2 broad categories.
  • Primary bone marrow involvement
    • Aplastic anemia
    • Myelophthisic anemia: Pathogenesis involves interruption of normal hematopoiesis due to the accumulation of malignant or reactive cells or cell products. It is characterized by the appearance of immature myeloid cells and nucleated RBCs in the peripheral blood. The 3 major classes of disorders that can produce myelophthisic anemia are intrinsic bone marrow malignancies (eg, leukemia, lymphoma, myeloma), metastatic tumors (eg, neuroblastoma, melanoma, cancers that are more prone to bone marrow metastasis (eg, prostate, breast, lung, stomach, renal carcinomas), and granulomatous disease (eg, tuberculosis, sarcoidosis).
    • Myeloid metaplasia is known as agnogenic myeloid metaplasia and involves gradual bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly with no known underlying systemic disorder.
  • Anemia secondary to underlying disease: Most cases of anemia in the world are secondary to an underlying disease. The marrow does not respond appropriately to microcytic anemia, leading to decreased production of RBC. This type of anemia includes liver cirrhosis, uremia, chronic inflammation, and hypoendocrine conditions (eg, thyroid, adrenal, pituitary disorders).
• Hemolytic anemias: This type of anemia includes sickle cell anemia, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, aortic valve prosthesis, disseminated intravascular coagulation (DIC), cold agglutinin disease, and paroxysmal cold hemoglobinuria (PCH).

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