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Anemia Clinical Presentation

  • Author: Joseph E Maakaron, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Jul 22, 2016


Carefully obtain a history and perform a physical examination in every patient with anemia, because the findings usually provide important clues to the underlying disorder. From the standpoint of the investigation of the anemia, asking questions in addition to those conventionally explored during a routine examination is important. Areas of inquiry found valuable are briefly described below.

Often, the duration of anemia can be established by obtaining a history of previous blood studies and, if necessary, by acquiring those records. Similarly, a history of rejection as a blood donor or prior prescription of hematinics provides clues that anemia was detected previously.

Obtain a careful family history not only for anemia but also for jaundice, cholelithiasis, splenectomy, bleeding disorders, and abnormal hemoglobins. Carefully document the patient's occupation, hobbies, prior medical treatment, drugs (including over-the-counter medications and vitamins), and household exposures to potentially noxious agents. Patients are unlikely to volunteer exposures to tranquilizers, insecticides, paints, solvents, and hair dyes unless specifically queried.

In searching for blood loss, carefully document pregnancies, abortions, and menstrual loss. Estimates of menstrual losses are notoriously inaccurate if only routine inquiry is made.

Often, patients do not appreciate the significance of tarry stools. Changes in bowel habits can be useful in uncovering neoplasms of the colon. Hemorrhoidal blood loss is difficult to quantify, and it may be overlooked or overestimated from one patient to another. Obviously, seek a careful history of gastrointestinal complaints that may suggest gastritis, peptic ulcers, hiatal hernias, or diverticula. Abnormal urine color can occur in renal and hepatic disease and in hemolytic anemia.

A thorough dietary history is important in a patient who is anemic. This history must include foods that the patient eats and those that he/she avoids, as well as an estimate of their quantity. A meal-by-meal description is necessary to obtain appropriate estimates. Even then, patients frequently attempt to deceive the physician because of embarrassment regarding dietary idiosyncrasies or financial restrictions. In these circumstances, having a close and concerned family member participate in the dietary history can often be helpful, because this person is usually more objective than the patient.

Specifically question patients regarding consumption of either clay or laundry starch. This history will not be provided spontaneously. These substances render iron less absorbable. Changes in body weight are important with regard to dietary intake and can suggest the presence of malabsorption or an underlying wasting disease of infectious, metabolic, or neoplastic origin.

Nutritional deficiencies may be associated with unusual symptoms that can be elicited by a history. Patients with iron deficiencies frequently chew or suck ice (pagophagia). Occasionally, they complain of dysphagia, brittle fingernails, relative impotence, fatigue, and cramps in the calves on climbing stairs that are out of proportion to their anemia.

In vitamin B-12 deficiency, early graying of the hair, a burning sensation in the tongue, and a loss of proprioception are common. Suspect a loss of proprioception if the patient stumbles in the dark or must look in order to put on pants in the morning. Paresthesia or unusual sensations frequently described as pain also occur in pernicious anemia.

Patients with folate deficiency may have a sore tongue, cheilosis, and symptoms associated with steatorrhea. Color, bulk, frequency, and odor of stools and whether the feces float or sink can be helpful in detecting malabsorption. More sensitive questions to detect steatorrhea include whether the toilet needs to be flushed more than once to rid it of stool and whether an oily substance is floating on the water surface after the first flush.

Obtain a history of fever or identify the presence of fever, because infections, neoplasms, and collagen vascular disease can cause anemia. Similarly, the occurrence of purpura, ecchymoses, and petechiae suggest the occurrence of either thrombocytopenia or other bleeding disorders; this may be an indication either that more than 1 bone marrow lineage is involved or that coagulopathy is a cause of the anemia because of bleeding.

Cold intolerance can be an important symptom of hypothyroidism or lupus erythematosus, paroxysmal cold hemoglobinuria, and certain macroglobulinemias.

The relation of dark urine to either physical activity or time of day can be important in march hemoglobinuria and paroxysmal nocturnal hemoglobinuria.

Explore the presence or the absence of symptoms suggesting an underlying disease, such as cardiac, hepatic, and renal disease; chronic infection; endocrinopathy; or malignancy. A geographic history can also be important in establishing an etiology.


Physical Examination

Too often, the physician rushes into the physical examination without looking at the patient for an unusual habitus or appearance of underdevelopment, malnutrition, or chronic illness. These findings can be important clues to the underlying etiology of disease and provide information related to the duration of illness. The skin and mucous membranes are often bypassed, so that pallor, abnormal pigmentation, icterus, spider nevi, petechiae, purpura, angiomas, ulcerations, palmar erythema, coarseness of hair, puffiness of the face, thinning of the lateral aspects of the eyebrows, nail defects, and a usually prominent venous pattern on the abdominal wall are missed in the rush to examine the heart and the lungs.

Examine optic fundi carefully but not at the expense of the conjunctivae and the sclerae, which can show pallor, icterus, splinter hemorrhages, petechiae, comma signs in the conjunctival vessels, or telangiectasia that can be helpful in planning additional studies.

Perform systematic examination for palpable enlargement of lymph nodes for evidence of infection or neoplasia. Bilateral edema is useful in disclosing underlying cardiac, renal, or hepatic disease, whereas unilateral edema may portend lymphatic obstruction due to a malignancy that cannot be observed or palpated.

Carefully search for hepatomegaly and splenomegaly. Their presence or absence is important, as are the size, the tenderness, the firmness, and the presence or the absence of nodules. In patients with chronic disorders, these organs are firm, nontender, and nonnodular. In patients with carcinoma, they may be hard and nodular. The patient with an acute infection usually has a palpably softer and more tender organ.

A rectal and pelvic examination cannot be neglected, because tumor or infection of these organs can be the cause of anemia.

The neurologic examination should include tests of position sense and vibratory sense, examination of the cranial nerves, and testing for tendon reflexes. The heart should not be ignored, because enlargement may provide evidence of the duration and the severity of the anemia, and murmurs may be the first evidence of a bacterial endocarditis that could explain the etiology of the anemia.

Contributor Information and Disclosures

Joseph E Maakaron, MD Research Fellow, Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.


Ali T Taher, MD, PhD, FRCP Professor of Medicine, Associate Chair of Research, Department of Internal Medicine, Division of Hematology/Oncology, Director of Research, NK Basile Cancer Center, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.


Jose A Perez Jr, MD, MBA, MSEd Consulting Staff, Department of Medicine, Methodist Hospital; Associate Professor of Clinical Medicine, Weill Cornell Medical College

Jose A Perez Jr, MD, MBA, MSEd is a member of the following medical societies: American College of Physician Executives, American College of Physicians, Society of General Internal Medicine, and Society of Hospital Medicine

Disclosure: Nothing to disclose.

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Veng-Pedersen P, Chapel S, Schmidt RL, Al-Huniti NH, Cook RT, Widness JA. An integrated pharmacodynamic analysis of erythropoietin, reticulocyte, and hemoglobin responses in acute anemia. Pharm Res. 2002 Nov. 19(11):1630-5. [Medline].

  2. Liang R, Ghaffari S. Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol. 2016 Jul 21. [Medline].

  3. Adamson JW, Longo DL. Anemia and polycythemia. Harrison's Principles of Internal Medicine. 15th ed. New York, New York: McGraw-Hill; 2001. Vol 1.: 348-354.

  4. Babushok DV, Li Y, Roth JJ, Perdigones N, Cockroft JD, Biegel JA, et al. Common polymorphic deletion of glutathione S-transferase theta predisposes to acquired aplastic anemia: Independent cohort and meta-analysis of 609 patients. Am J Hematol. 2013 Oct. 88 (10):862-7. [Medline]. [Full Text].

  5. Hung M, Besser M, Sharples LD, Nair SK, Klein AA. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients. Anaesthesia. 2011 Sep. 66(9):812-8. [Medline].

  6. Servilla KS, Singh AK, Hunt WC, et al. Anemia management and association of race with mortality and hospitalization in a large not-for-profit dialysis organization. Am J Kidney Dis. 2009 Sep. 54(3):498-510. [Medline].

  7. Adebisi OY, Strayhorn G. Anemia in pregnancy and race in the United States: blacks at risk. Fam Med. 2005 Oct. 37(9):655-62. [Medline].

  8. Silva DG, Priore SE, Franceschini Sdo C. Risk factors for anemia in infants assisted by public health services: the importance of feeding practices and iron supplementation. J Pediatr (Rio J). 2007 Mar-Apr. 83(2):149-56. [Medline].

  9. Oliveira MA, Osorio MM, Raposo MC. Socioeconomic and dietary risk factors for anemia in children aged 6 to 59 months. J Pediatr (Rio J). 2007 Jan-Feb Epub 2007 Jan 12. 83(1):39-46. [Medline].

  10. Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct. 89(10):1187-93. [Medline].

  11. Kuku I, Kaya E, Yologlu S, Gokdeniz R, Baydin A. Platelet counts in adults with iron deficiency anemia. Platelets. 2009 Aug 3. 1-5. [Medline].

  12. Stamatoyannopoulos G, Majerus PW, Perimutter RM. The Molecular Basis of Blood Diseases. Philadelphia, Pa: WB Saunders Co; 2000.

  13. Dhar R, Zazulia AR, Videen TO, et al. Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage. Stroke. 2009 Sep. 40(9):3039-44. [Medline]. [Full Text].

  14. DeLoughery TG. Microcytic anemia. N Engl J Med. 2014 Oct 2. 371(14):1324-31. [Medline].

  15. Mozaffari-Khosravi H, Noori-Shadkam M, Fatehi F, Naghiaee Y. Once weekly low-dose iron supplementation effectively improved iron status in adolescent girls. Biol Trace Elem Res. 2009 Aug 4. epub ahead of print. [Medline].

  16. [Guideline] Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan. 172 (2):187-207. [Medline]. [Full Text].

  17. [Guideline] Barone A, Lucarelli A, Onofrillo D, Verzegnassi F, Bonanomi S, et al. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP). Blood Cells Mol Dis. 2015 Jun. 55 (1):40-7. [Medline].

Anemia. Decreased production of red blood cells is suggested in certain patients with anemia. Bone marrow biopsy specimen allows categorization of patients with anemia without evidence of blood loss or hemolysis into 3 groups: aplastic or hypoplastic disorder, hyperplastic disorder, or infiltration disorder. Each category and its associated causes are listed in this image.
Microcytic anemia.
Peripheral smear showing classic spherocytes with loss of central pallor in the erythrocytes.
Bone marrow aspirate containing increased numbers of plasma cells.
Bone marrow aspirate showing erythroid hyperplasia and many binucleated erythroid precursors.
Table 1. Microcytic Hypochromic Anemia (MCV < 83; MCHC < 31)
Condition Serum Iron Total Iron-Binding Capacity (TIBC) Bone Marrow Iron Comment
Iron deficiency 0 Responsive to iron therapy
Chronic inflammation ++ Unresponsive to iron therapy
Thalassemia major N ++++ Reticulocytosis and indirect bilirubinemia
Thalassemia minor N N - ↓ ++ Elevation of fetal hemoglobin and Hb A2, target cells, and poikilocytosis
Lead poisoning N N ++ Basophilic stippling of RBCs
Sideroblastic N ++++ Ring sideroblasts in marrow
Hemoglobin N N ++ Hemoglobin electrophoresis
↓ = decreased; ↑ = increased; 0 = absent; +'s indicate the amount of stainable iron in bone marrow specimens, on a scale of 0-4; N = normal.
Table 2. Macrocytic Anemia (MCV >95)
Megaloblastic bone marrow Deficiency of vitamin B-12
Deficiency of folic acid
Drugs affecting deoxyribonucleic acid (DNA) synthesis
Inherited disorders of DNA synthesis
Nonmegaloblastic bone marrow Liver disease
Hypothyroidism and hypopituitarism
Accelerated erythropoiesis (reticulocytes)
Hypoplastic and aplastic anemia
Infiltrated bone marrow
Table 3. Various Forms of RBCs
Macrocyte Larger than normal (>8.5 µm diameter). See Table 2.
Microcyte Smaller than normal (< 7 µm diameter). See Table 1.
Hypochromic Less hemoglobin in cell. Enlarged area of central pallor. See Table 1.
Spherocyte Loss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and certain acquired hemolytic anemias
Target cell Hypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, and postsplenectomy
Leptocyte Hypochromic cell with a normal diameter and decreased MCV. Thalassemia
Elliptocyte Oval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B-12 and folate deficiency)
Schistocyte Fragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, and malignant hypertension
Stomatocyte Slitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact
Tear-shaped RBCs Drop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia
Acanthocyte Five to 10 spicules of various lengths and at irregular intervals on surface of RBCs
Echinocyte Evenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency, and preparative artifact
Sickle cell Elongated cell with pointed ends. Hemoglobin S and certain types of hemoglobin C and l
Table 4. Classification of the Hemolytic Disorders
  Hereditary Acquired
Intracorpuscular defect Hereditary spherocytosis

Hereditary elliptocytosis



Congenital dyserythropoietic anemias

Hereditary RBC enzymatic deficiencies

Rarer hereditary abnormalities

Vitamin B-12 and folic acid deficiency

Paroxysmal nocturnal hemoglobinuria

Severe iron deficiency

Extracorpuscular defect   Physical agents: Burns, cold exposure

Traumatic: Prosthetic heart valves, march hemoglobinuria, disseminated intravascular coagulation (DIC), graft rejection

Chemicals: Drugs and venoms

Infectious agents: Malaria, toxoplasmosis, mononucleosis, hepatitis, primary atypical pneumonia, clostridial infections, bartonellosis, leishmaniasis

Hepatic and renal disease

Collagen vascular disease

Malignancies: Particularly hematologic neoplasia

Transfusion of incompatible blood

Hemolytic disease of the newborn

Cold hemagglutinin


Autoimmune hemolytic anemia Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS)

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