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Anemia Differential Diagnoses

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

Diagnostic Considerations

Many symptoms associated with anemia are not caused by diminished RBC mass. For example, ice chewing, calf cramps, and diminished capability to perform muscular work occur in iron deficiency anemia with a hemoglobin (Hb) level of 10-11 g/dL because of depletion of iron-containing proteins other than Hb.[11] Pernicious anemia is often detected incidentally in patients who are asymptomatic despite an Hb level as low as 6 g/dL.

Tolerance of anemia is proportional to the anemia's rate of development. Symptoms and mortality associated with rapidly developing anemia are more profound than in slowly developing anemia.

Differential Diagnoses

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

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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)
ConditionSerum IronTotal Iron-Binding Capacity (TIBC)Bone Marrow IronComment
Iron deficiency0Responsive to iron therapy
Chronic inflammation++Unresponsive to iron therapy
Thalassemia majorN++++Reticulocytosis and indirect bilirubinemia
Thalassemia minorNN - ↓++Elevation of fetal hemoglobin and Hb A2, target cells, and poikilocytosis
Lead poisoningNN++Basophilic stippling of RBCs
SideroblasticN++++Ring sideroblasts in marrow
HemoglobinNN++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 marrowDeficiency of vitamin B-12
Deficiency of folic acid
Drugs affecting deoxyribonucleic acid (DNA) synthesis
Inherited disorders of DNA synthesis
Nonmegaloblastic bone marrowLiver disease
Hypothyroidism and hypopituitarism
Accelerated erythropoiesis (reticulocytes)
Hypoplastic and aplastic anemia
Infiltrated bone marrow
Table 3. Various Forms of RBCs
MacrocyteLarger than normal (>8.5 µm diameter). See Table 2.
MicrocyteSmaller than normal (< 7 µm diameter). See Table 1.
HypochromicLess hemoglobin in cell. Enlarged area of central pallor. See Table 1.
SpherocyteLoss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and certain acquired hemolytic anemias
Target cellHypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, and postsplenectomy
LeptocyteHypochromic cell with a normal diameter and decreased MCV. Thalassemia
ElliptocyteOval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B-12 and folate deficiency)
SchistocyteFragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, and malignant hypertension
StomatocyteSlitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact
Tear-shaped RBCsDrop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia
AcanthocyteFive to 10 spicules of various lengths and at irregular intervals on surface of RBCs
EchinocyteEvenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency, and preparative artifact
Sickle cellElongated cell with pointed ends. Hemoglobin S and certain types of hemoglobin C and l
Table 4. Classification of the Hemolytic Disorders
Intracorpuscular defectHereditary 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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