Medscape is available in 5 Language Editions – Choose your Edition here.


Pediatric Chronic Anemia Clinical Presentation

  • Author: Susumu Inoue, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
Updated: Apr 12, 2016


Patients with chronic anemia are usually asymptomatic, even with remarkably low levels of hemoglobin.

Symptoms more often relate to the underlying cause; for example, irritability, pagophasia (ice eating), and lethargy can occur if the anemia is secondary to iron deficiency; paresthesia of hands and feet, if the anemia is due to vitamin B-12 deficiency; left upper quadrant pain, if the anemia is the result of HS and splenomegaly; intolerance to fatty foods, if the anemia is caused by chronic hemolysis with subsequent cholelithiasis; and constipation and cold intolerance, if the anemia is the result of hypothyroidism. Undetected celiac disease or renal failure sometimes manifest as chronic anemia and failure to thrive. Diarrhea and intermittent abdominal pain and chronic anemia may be due to Crohn disease or celiac disease.

Hemoglobin levels as low as 5-6 g/dL are well tolerated in most patients, and patients do not require transfusion. Parents, however, frequently note that patients become much more active following a transfusion.

Inquire carefully regarding any evidence of blood loss (eg, hemoptysis, hematochezia, melena, hematuria, menorrhagia). In endemic areas, a history of papulovesicular skin lesions on the feet may suggest a diagnosis of hookworm infestation.

Age is always an important consideration. Nutritional iron deficiency is seen in older infants and toddlers (aged 6 mo to 3 y), whereas iron deficiency due to blood loss occurs in menstruating girls. The deficiency can be surprisingly severe, but transfusion is indicated only in the rare circumstance of impending high-output cardiac failure.

The patient's sex must always be considered in hemolytic anemias. Severe G-6-PD deficiency may be seen as a chronic nonspherocytic anemia, usually in males.

Ethnicity is a factor in the hemoglobinopathies. Hemoglobin S syndromes are usually seen in populations of central African origin. Hemoglobin C syndromes are seen in populations of western African origin. Hemoglobin D syndromes are usually seen in the population of northern India. Hemoglobin E syndromes are seen in populations of Southeast Asia. Beta-thalassemias are seen in Mediterranean, Middle Eastern, Indian, and Southeast Asian populations. Thalassemias involving the β chain are clinically silent in the first months of life and become apparent only after 6-9 months because of cessation of γ-chain production. Alpha-thalassemias are seen in African, Middle Eastern, and Asian populations.

Dietary history is important with regard to the amount and source of milk ingested by infants and toddlers and to their risk of chronic iron deficiency (24 oz of milk/d or more is a clear risk factor for nutritional iron deficiency in infants and young children). Food aversions (eg, to leafy vegetables) can cause predisposition to folic acid deficiency. Folic acid deficiency also occurs in children fed exclusively with goat's milk. Certain diets (eg, vegan diet) can result in vitamin B-12 deficiency if continued over several years.

Blood loss over an extended period results in iron deficiency. Chronic infection or inflammation, such as chronic pyelonephritis, bacterial endocarditis, osteomyelitis, or juvenile idiopathic arthritis, results in the anemia of chronic disease. Any inflammatory process, such as chronic renal failure or a chronic collagen vascular disease, also results in the anemia of chronic disease. Episodic pain in the chest, abdomen, or extremities may be due to a vasoocclusive crisis of sickle cell disease.

Drugs with oxidant properties trigger hemolysis because of a G-6-PD deficiency, and hemolysis may become chronic if the drugs are continued for an extended period. Exposure to known marrow toxins, such as benzene or the antibiotic chloramphenicol, may result in aplastic anemia months after actual exposure.

Neonatal history may provide useful information regarding a possibly overlooked congenital process that manifested after birth. Exaggerated jaundice as a newborn may be a clue for HS or G-6-PD deficiency.

Family history is critical in any hereditary anemia. Anemia occurs in families with thalassemia syndromes. Gallstones, early cholecystectomy, and splenomegaly are common in families with HS.


Physical Examination

Vital signs, in contrast to those in acute anemia (such as anemia due to acute blood loss), are rarely abnormal in patients with chronic anemias, because adaptive mechanisms are well developed. Tachycardia on exertion is usually the only exception to this rule.

Growth curves may be affected by chronic anemia, usually in a symmetrical fashion, although head circumference is not affected.

Fanconi anemia is characterized by some or all of the following dysmorphic features: small stature, small head, absent thumbs, and café-au-lait spots.

Chronic hemolysis with extramedullary hematopoiesis, such as in β-thalassemia major or sickle cell anemia, may result in frontal bossing and prominent cheeks.

Pallor may be difficult to appreciate unless carefully sought. Pallor of the conjunctivae, nail beds, palm creases, or gums may be recognized. Parents and friends usually do not notice any difference, because the problem is chronic.

Scleral icterus is common in chronic hemolytic anemia. The icterus waxes and wanes.

Petechiae and excessive bruises may indicate thrombocytopenia resulting from marrow aplasia or replacement by malignant cells. Less commonly, the same findings may reflect vasculitis resulting from infection or collagen vascular disease.

Papulovesicular lesions on the feet may suggest hookworm infestation.

Systolic murmur may be apparent and is usually loudest along the left sternal border, as is appropriate in any flow murmur.

Gallop rhythm, cardiomegaly, and hepatic enlargement may indicate early congestive heart failure.

Splenomegaly may indicate chronic hemolysis, as in HS, or elliptocytosis. It may also suggest hypersplenism due to many causes, such as portal hypertension or storage disease. Hypersplenism usually causes mild leukopenia and thrombocytopenia as well. Splenomegaly may also indicate leukemia, myelofibrosis, myeloproliferative disorder, or myelodysplastic syndrome.

Contributor Information and Disclosures

Susumu Inoue, MD Professor of Pediatrics and Human Development, Michigan State University College of Human Medicine; Clinical Professor of Pediatrics, Wayne State University School of Medicine; Director of Pediatric Hematology/Oncology, Associate Director of Pediatric Education, Department of Pediatrics, Hurley Medical Center

Susumu Inoue, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.


John T Truman, MD, MPH Professor Emeritus of Clinical Pediatrics, Columbia University College of Physicians and Surgeons

John T Truman, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American Association for the History of Medicine, American Society of Pediatric Nephrology, New York Academy of Medicine

Disclosure: Nothing to disclose.

Margaret T Lee, MD Associate Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology/SCT, Children's Hospital of New York, Columbia University College of Physicians and Surgeons

Margaret T Lee, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

  1. Dowling MM, Quinn CT, Plumb P, Rogers ZR, Rollins NK, Koral K. Acute silent cerebral ischemia and infarction during acute anemia in children with and without sickle cell disease. Blood. 2012 Nov 8. 120(19):3891-7. [Medline].

  2. Baker C, Grant AM, George MG, Grosse SD, Adamkiewicz TV. Contribution of Sickle Cell Disease to the Pediatric Stroke Burden Among Hospital Discharges of African-Americans-United States, 1997-2012. Pediatr Blood Cancer. 2015 Dec. 62 (12):2076-81. [Medline].

  3. Skeppner G, Kreuger A, Elinder G. Transient erythroblastopenia of childhood: prospective study of 10 patients with special reference to viral infections. J Pediatr Hematol Oncol. 2002 May. 24(4):294-8. [Medline].

  4. Penchansky L, Jordan JA. Transient erythroblastopenia of childhood associated with human herpesvirus type 6, variant B. Am J Clin Pathol. 1997 Aug. 108(2):127-32. [Medline].

  5. Prassouli A, Papadakis V, Tsakris A, Stefanaki K, Garoufi A, Haidas S. Classic transient erythroblastopenia of childhood with human parvovirus B19 genome detection in the blood and bone marrow. J Pediatr Hematol Oncol. 2005 Jun. 27(6):333-6. [Medline].

  6. Iolascon A, Camaschella C, Pospisilova D, Piscopo C, Tchernia G, Beaumont C. Natural history of recessive inheritance of DMT1 mutations. J Pediatr. 2008 Jan. 152(1):136-9. [Medline].

  7. Global Burden of Disease Pediatrics Collaboration, Kyu HH, Pinho C, et al. Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013: Findings From the Global Burden of Disease 2013 Study. JAMA Pediatr. 2016 Mar 1. 170 (3):267-87. [Medline].

  8. Henderson S, Timbs A, McCarthy J, Gallienne A, Van Mourik M, Masters G. Incidence of haemoglobinopathies in various populations - the impact of immigration. Clin Biochem. 2009 Dec. 42(18):1745-56. [Medline].

  9. Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med. 2012 Sep. 2(9):a011692. [Medline].

  10. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010 Jun 3. 115(22):4331-6. [Medline].

  11. Baker RD, Greer FR. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010 Nov. 126(5):1040-50. [Medline].

  12. Lozoff B, Castillo M, Clark KM, Smith JB. Iron-fortified vs low-iron infant formula: developmental outcome at 10 years. Arch Pediatr Adolesc Med. 2012 Mar. 166(3):208-15. [Medline]. [Full Text].

  13. Wiseman DH, May A, Jolles S, et al. A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood. 2013 Jul 4. 122 (1):112-23. [Medline]. [Full Text].

  14. Iolascon A, De Falco L. Mutations in the gene encoding DMT1: clinical presentation and treatment. Semin Hematol. 2009 Oct. 46(4):358-70. [Medline].

  15. Finberg KE. Iron-refractory iron deficiency anemia. Semin Hematol. 2009 Oct. 46(4):378-86. [Medline].

Blood smear from a black male with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency that resulted in acute hemolysis. Note blister (helmet or bite) cells and very dense spherocytic cells. The blood smear is virtually pathognomic of this disorder.
Blood smear of hereditary spherocytosis (HS). Note many spherocytic cells. Not all patients with HS are anemic.
Blood smear of hemoglobin C trait. Note numerous target cells. Target cells are a characteristic of this hemoglobinopathy. The trait patient has no anemia. Target cells are also seen in patients with iron deficiency anemia, thalassemia, sickle cell disease, and liver disease.
Blood smear of a patient with homozygous sickle cell disease. Note several sickle cells, a nucleated RBC, and a red cell with Howell-Jolly body (indicated by an arrow), evidence of functional asplenia.
A blood smear showing a few schistocytes. This patient had Kaposi type hemangioendothelioma with periodic microangiopathic hemolysis and disseminated coagulopathy (Kasabach-Merritt phenomenon).
A blood smear of a patient with beta thalassemia trait. Note red cells pointed by arrows. Multiple bluish dots in the cells are called basophilic stipplings and consist of aggregated ribosomes. They are often present in immature red cells such as reticulocytes.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.