Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Approach to the adult patient with anemia

Stanley L Schrier, MD
Section Editor
William C Mentzer, MD
Deputy Editor
Jennifer S Tirnauer, MD


Evaluation for anemia is one of the most common problems seen in clinical practice. While the evaluation may be straightforward in an otherwise healthy individual with a single cause of anemia, in many cases the cause is not readily apparent and multiple conditions may be contributing.

An overview of the causes of anemia and an approach to the evaluation of the adult with unexplained anemia are presented here.

Specific causes of anemia and the evaluation of specific patient populations are discussed in more detail in separate topic reviews:

Iron deficiency – (see "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults")

B12 and folate deficiency – (see "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency")

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Sep 26, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Causey MW, Miller S, Foster A, et al. Validation of noninvasive hemoglobin measurements using the Masimo Radical-7 SpHb Station. Am J Surg 2011; 201:592.
  2. Shamir MY, Avramovich A, Smaka T. The current status of continuous noninvasive measurement of total, carboxy, and methemoglobin concentration. Anesth Analg 2012; 114:972.
  3. Kim SH, Lilot M, Murphy LS, et al. Accuracy of continuous noninvasive hemoglobin monitoring: a systematic review and meta-analysis. Anesth Analg 2014; 119:332.
  4. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 2006; 107:1747.
  5. World Health Organization. Nutritional anaemias: Report of a WHO scientific group. Geneva, Switzerland: World Health Organization; 1968.
  6. Rodgers GM 3rd, Becker PS, Bennett CL, et al. Cancer- and chemotherapy-induced anemia. J Natl Compr Canc Netw 2008; 6:536.
  7. Ruíz-Argüelles GJ. Altitude above sea level as a variable for definition of anemia. Blood 2006; 108:2131; author reply 2131.
  8. Stewart RD, Baretta ED, Platte LR, et al. Carboxyhemoglobin levels in American blood donors. JAMA 1974; 229:1187.
  9. Nordenberg D, Yip R, Binkin NJ. The effect of cigarette smoking on hemoglobin levels and anemia screening. JAMA 1990; 264:1556.
  10. Garn SM, Ryan AS, Abraham S, Owen G. Suggested sex and age appropriate values for "low" and "deficient" hemoglobin levels. Am J Clin Nutr 1981; 34:1648.
  11. Reed WW, Diehl LF. Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American blacks. Arch Intern Med 1991; 151:501.
  12. Perry GS, Byers T, Yip R, Margen S. Iron nutrition does not account for the hemoglobin differences between blacks and whites. J Nutr 1992; 122:1417.
  13. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006; 119:327.
  14. Robins EB, Blum S. Hematologic reference values for African American children and adolescents. Am J Hematol 2007; 82:611.
  15. Beutler E, West C. Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood 2005; 106:740.
  16. Culleton BF, Manns BJ, Zhang J, et al. Impact of anemia on hospitalization and mortality in older adults. Blood 2006; 107:3841.
  17. Patel KV, Harris TB, Faulhaber M, et al. Racial variation in the relationship of anemia with mortality and mobility disability among older adults. Blood 2007; 109:4663.
  18. Toda S, Segawa K, Nagata S. MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands. Blood 2014; 123:3963.
  19. Hattangadi SM, Martinez-Morilla S, Patterson HC, et al. Histones to the cytosol: exportin 7 is essential for normal terminal erythroid nuclear maturation. Blood 2014; 124:1931.
  20. Clinical approach to anemia. In: Hematology in Clinical Practice, Hillman RS, Ault KA (Eds), McGraw-Hill, New York 2001. p.29.
  21. Erslev AJ. Reticulocyte enumeration. In: Williams' Hematology, 5th ed, Beutler E, Lichtman MA, Coller BS, et al. (Eds), McGraw-Hill, New York 1995. p.L28.
  22. Jacob G, Raj SR, Ketch T, et al. Postural pseudoanemia: posture-dependent change in hematocrit. Mayo Clin Proc 2005; 80:611.
  23. Valeri CR, Dennis RC, Ragno G, et al. Limitations of the hematocrit level to assess the need for red blood cell transfusion in hypovolemic anemic patients. Transfusion 2006; 46:365.
  24. Normal erythropoiesis. In: Hematology in Clinical Practice, Hillman RS, Ault KA (Eds), McGraw-Hill, New York 2001. p.3.
  25. Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279:217.
  26. Jones J. Transfusion in oligemia. In: Blood Transfusion in Clinical Medicine, 8th ed, Mollison PL, Engelfriet CP, Contreras M (Eds), Blackwell, Oxford 1987. p.41.
  27. Uhl L, Assmann SF, Hamza TH, et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood 2017; 130:1247.
  28. Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med 2013; 8:506.
  29. Tefferi A. Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc 2003; 78:1274.
  30. Gomes ME, Deinum J, Timmers HJ, Lenders JW. Occam's razor; anaemia and orthostatic hypotension. Lancet 2003; 362:1282.
  31. Perera R, Isola L, Kaufmann H. Effect of recombinant erythropoietin on anemia and orthostatic hypotension in primary autonomic failure. Clin Auton Res 1995; 5:211.
  32. Hara A, Furuichi K, Higuchi M, et al. Autoantibodies to erythropoietin receptor in patients with immune-mediated diseases: relationship to anaemia with erythroid hypoplasia. Br J Haematol 2013; 160:244.
  33. Mohandas N, Schrier SL. Mechanisms of red cell destruction in hemolytic anemias. In: The Hereditary Hemolytic Anemias, Mentzer WC, Wagner GM (Eds), Churchill Livingstone, New York 1989. p.391.
  34. Karamanou M, Androutsos G. Lasthénie de Ferjol syndrome: a rare disease with fascinating history. Intern Med J 2010; 40:381.
  35. Piccillo GA, Miele L, Mondati EG, et al. Eighteen needles to forget...an unnamed past. J Forensic Leg Med 2007; 14:304.
  36. Farcy L, Fillet G, Couvreur V, Triffaux JM. [Anemia by self-injury: the Lasthenie de Ferjol syndrome]. Rev Med Liege 2005; 60:719.
  37. González C, Penado S, Llata L, et al. The clinical spectrum of retroperitoneal hematoma in anticoagulated patients. Medicine (Baltimore) 2003; 82:257.
  38. Salisbury AC, Reid KJ, Alexander KP, et al. Diagnostic blood loss from phlebotomy and hospital-acquired anemia during acute myocardial infarction. Arch Intern Med 2011; 171:1646.
  39. Thavendiranathan P, Bagai A, Ebidia A, et al. Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels. J Gen Intern Med 2005; 20:520.
  40. Bull BS, Breton-Gorius J. Morphology of the erythron. In: Williams' Hematology, 5th ed, Beutler E, Lichtman MA, Coller BS, Kipps TJ (Eds), McGraw-Hill, New York 1995. p.349.
  41. Morris MW, Williams WJ, Nelson DA. Automated blood cell counting. In: Williams' Hematology, 5th ed, Beutler E, Lichtman MA, Coller BS, et al. (Eds), McGraw-Hill, New York 1995. p.L3.
  42. Davenport J. Macrocytic anemia. Am Fam Physician 1996; 53:155.
  43. Inelmen EM, D'Alessio M, Gatto MR, et al. Descriptive analysis of the prevalence of anemia in a randomly selected sample of elderly people living at home: some results of an Italian multicentric study. Aging (Milano) 1994; 6:81.
  44. Camaschella C. How I manage patients with atypical microcytic anaemia. Br J Haematol 2013; 160:12.
  45. Donker AE, Raymakers RA, Vlasveld LT, et al. Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis. Blood 2014; 123:3873.
  46. Bergstrome JA, Poon A. Evaluation of a single-tube multiplex polymerase chain reaction screen for detection of common alpha-thalassemia genotypes in a clinical laboratory. Am J Clin Pathol 2002; 118:18.
  47. Kazory A, Ross EA. Anemia: the point of convergence or divergence for kidney disease and heart failure? J Am Coll Cardiol 2009; 53:639.
  48. Shander A. Anemia in the critically ill. Crit Care Clin 2004; 20:159.
  49. Napolitano LM. Scope of the problem: epidemiology of anemia and use of blood transfusions in critical care. Crit Care 2004; 8 Suppl 2:S1.
  50. Steensma DP, Hoyer JD, Fairbanks VF. Hereditary red blood cell disorders in middle eastern patients. Mayo Clin Proc 2001; 76:285.
  51. Nardone DA, Roth KM, Mazur DJ, McAfee JH. Usefulness of physical examination in detecting the presence or absence of anemia. Arch Intern Med 1990; 150:201.
  52. Gjørup T, Bugge PM, Hendriksen C, Jensen AM. A critical evaluation of the clinical diagnosis of anemia. Am J Epidemiol 1986; 124:657.
  53. Hung OL, Kwon NS, Cole AE, et al. Evaluation of the physician's ability to recognize the presence or absence of anemia, fever, and jaundice. Acad Emerg Med 2000; 7:146.
  54. Sheth TN, Choudhry NK, Bowes M, Detsky AS. The relation of conjunctival pallor to the presence of anemia. J Gen Intern Med 1997; 12:102.
  55. Ruiz MA, Saab S, Rickman LS. The clinical detection of scleral icterus: observations of multiple examiners. Mil Med 1997; 162:560.
  56. Williams WJ, Morris MW, Nelson DA. Examination of the blood. In: Williams' Hematology, 5th ed, Beutler E, Lichtman MA, Coller BS, et al. (Eds), McGraw-Hill, New York 1995. p.8.
  57. Weiss GB, Bessman JD. Spurious automated red cell values in warm autoimmune hemolytic anemia. Am J Hematol 1984; 17:433.
  58. Xu X. Nuclear hypersegmentation of neutrophils, eosinophils, and basophils due to hydroxycarbamide (hydroxyurea). Blood 2014; 124:1392.
  59. Westerman DA, Evans D, Metz J. Neutrophil hypersegmentation in iron deficiency anaemia: a case-control study. Br J Haematol 1999; 107:512.
  60. Stachon A, Sondermann N, Imohl M, Krieg M. Nucleated red blood cells indicate high risk of in-hospital mortality. J Lab Clin Med 2002; 140:407.
  61. Marchand A, Galen RS, Van Lente F. The predictive value of serum haptoglobin in hemolytic disease. JAMA 1980; 243:1909.
  62. Galen RS. Application of the predictive value model in the analysis of test effectiveness. Clin Lab Med 1982; 2:685.
  63. Serjeant GR, Serjeant BE, Thomas PW, et al. Human parvovirus infection in homozygous sickle cell disease. Lancet 1993; 341:1237.
  64. Silverberg DS, Wexler D, Iaina A, Schwartz D. The interaction between heart failure and other heart diseases, renal failure, and anemia. Semin Nephrol 2006; 26:296.
  65. Dufaux B, Hoederath A, Streitberger I, et al. Serum ferritin, transferrin, haptoglobin, and iron in middle- and long-distance runners, elite rowers, and professional racing cyclists. Int J Sports Med 1981; 2:43.
  66. Shaskey DJ, Green GA. Sports haematology. Sports Med 2000; 29:27.
  67. Rudzki SJ, Hazard H, Collinson D. Gastrointestinal blood loss in triathletes: it's etiology and relationship to sports anaemia. Aust J Sci Med Sport 1995; 27:3.
  68. Selby GB, Eichner ER. Endurance swimming, intravascular hemolysis, anemia, and iron depletion. New perspective on athlete's anemia. Am J Med 1986; 81:791.
  69. Berglund B. High-altitude training. Aspects of haematological adaptation. Sports Med 1992; 14:289.
  70. Kehat I, Shupak A, Goldenberg I, Shoshani O. Long-term hematological effects in Special Forces trainees. Mil Med 2003; 168:116.
  71. Sawka MN, Convertino VA, Eichner ER, et al. Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness. Med Sci Sports Exerc 2000; 32:332.
  72. Greydanus DE, Patel DR. The female athlete. Before and beyond puberty. Pediatr Clin North Am 2002; 49:553.
  73. Beard J, Tobin B. Iron status and exercise. Am J Clin Nutr 2000; 72:594S.
  74. Peeling P, Dawson B, Goodman C, et al. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol 2008; 103:381.
Topic Outline