Smith ML. Anemia: Evaluation of Suspected Anemia. FP Essent. 2023 Jul. 530:7-11. [QxMD MEDLINE Link].
Garcia-Casal MN, Dary O, Jefferds ME, Pasricha SR. Diagnosing anemia: Challenges selecting methods, addressing underlying causes, and implementing actions at the public health level. Ann N Y Acad Sci. 2023 Jun. 1524 (1):37-50. [QxMD MEDLINE Link].
Liang R, Ghaffari S. Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol. 2016 Jul 21. [QxMD MEDLINE Link].
Adamson JW, Longo DL. Anemia and polycythemia. Loscalzo J, Fauci AS, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 21st ed. New York, New York: McGraw-Hill; 2022. Vol 1.: 431-438.
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Krishnasivam D, Trentino KM, Burrows S, Farmer SL, Picardo S, Leahy MF, et al. Anemia in hospitalized patients: an overlooked risk in medical care. Transfusion. 2018 Oct 1. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Adebisi OY, Strayhorn G. Anemia in pregnancy and race in the United States: blacks at risk. Fam Med. 2005 Oct. 37(9):655-62. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Kuku I, Kaya E, Yologlu S, Gokdeniz R, Baydin A. Platelet counts in adults with iron deficiency anemia. Platelets. 2009 Aug 3. 1-5. [QxMD MEDLINE Link].
An R, Huang Y, Man Y, Valentine RW, Kucukal E, Goreke U, et al. Emerging point-of-care technologies for anemia detection. Lab Chip. 2021 May 18. 21 (10):1843-1865. [QxMD MEDLINE Link].
Ramaswamy G, Vohra K, Yadav K, Kaur R, Rai T, Jaiswal A, et al. Point-of-Care Testing Using Invasive and Non-Invasive Hemoglobinometers: Reliable and Valid Method for Estimation of Hemoglobin among Children 6-59 Months. J Trop Pediatr. 2021 Jan 29. 67 (1):[QxMD MEDLINE Link].
Clemente F, Antonacci A, Giardi MT, Frisulli V, Tambaro FP, Scognamiglio V. Last Trends in Point-of-Care (POC) Diagnostics for the Management of Hematological Indices in Home Care Patients. Biosensors (Basel). 2023 Mar 4. 13 (3):[QxMD MEDLINE Link]. [Full Text].
Piriyakhuntorn P, Tantiworawit A, Rattanathammethee T, Chai-Adisaksopha C, Rattarittamrong E, Norasetthada L. The role of red cell distribution width in the differential diagnosis of iron deficiency anemia and non-transfusiondependent thalassemia patients. Hematol Rep. 2018 Sep 5. 10 (3):7605. [QxMD MEDLINE Link]. [Full Text].
Stamatoyannopoulos G, Majerus PW, Perimutter RM. The Molecular Basis of Blood Diseases. Philadelphia, Pa: WB Saunders Co; 2000.
[Guideline] Shander A, Corwin HL, Meier J, Auerbach M, Bisbe E, Blitz J, et al. Recommendations From the International Consensus Conference on Anemia Management in Surgical Patients (ICCAMS). Ann Surg. 2023 Apr 1. 277 (4):581-590. [QxMD MEDLINE Link]. [Full Text].
[Guideline] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Hematopoietic Growth Factors. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf. Version 2.2023 — March 6, 2023; Accessed: August 24, 2023.
Cappellini MD, Viprakasit V, Taher A, et al. The Believe trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept in adult beta-thalassemia patients who require regular red blood cell (RBC) transfusions. Abstract #163. Presented at the 2018 American Society of Hematology (ASH) Annual Meeting, December 1, 2018; San Diego, CA.
[Guideline] Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK, et al. Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med. 2012 Jul 3. 157 (1):49-58. [QxMD MEDLINE Link]. [Full Text].
Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22. 126 (17):1981-9. [QxMD MEDLINE Link]. [Full Text].
Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020 May. 105 (5):1232-1239. [QxMD MEDLINE Link]. [Full Text].
Uçan A, Kaya ZI, Yilmaz EÖ, Vasi İ, Özgeyik MO. Comparing therapeutic effects of alternate day versus daily oral iron in women with iron deficiency anemia: A retrospective cohort study. Medicine (Baltimore). 2023 Jul 28. 102 (30):e34421. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
DeLoughery TG. Microcytic anemia. N Engl J Med. 2014 Oct 2. 371(14):1324-31. [QxMD MEDLINE Link].
[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. [QxMD MEDLINE Link]. [Full Text].
[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. [QxMD MEDLINE Link].
Schuetz C, Hoenig M, Moshous D, Weinstock C, Castelle M, Bendavid M, et al. Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation. Blood Adv. 2018 Oct 9. 2 (19):2550-2553. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

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.

of 5

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 B12
	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 B12 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

Hemoglobinopathies

Thalassemias

Congenital dyserythropoietic anemias

Hereditary RBC enzymatic deficiencies

Rarer hereditary abnormalities

Vitamin B12 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

disease

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

Back to List

Author

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.

Coauthor(s)

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, The Society of Federal Health Professionals (AMSUS), 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.

Acknowledgements

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

Anemia Questions & Answers

References

Tables

Contributor Information and Disclosures

What would you like to print?