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anemia

Any condition in which there is a reduction of either: 1) hemoglobin concentration 2) erythrocyte count 3) volume of packed erythrocytes Classification: 1) microcytic a) iron-deficiency anemia b) thalassemia c) anemia of chronic disease d) sideroblastic anemia e) lead poisoning f) unstable hemoglobins g) hemoglobin E 2) normocytic a) anemia of chronic disease (most common) b) acute hemorrhage c) endocrinopathy d) HIV-related anemia e) dilutional f) sports anemia g) mixed anemias h) myelophthisic anemia i) liver disease j) uremia j) hemoglobinopathy k) chronic renal failure 3) macrocytic a) pure red cell aplasia b) alcoholism c) aplastic anemia d) myelodysplastic syndrome e) megaloblastic anemia - vitamin B12 deficiency - folate deficiency f) hemolytic anemia g) cold agglutinin disease h) hypothyroidism* i) pharmaceutical agents * may be normocytic [18] Etiology: 1) blood loss including excessive phlebotomy 2) decreased red blood cell (RBC) production a) anemia of chronic inflammation b) anemia of chronic renal failure 3) increased RBC destruction (hemolysis) 4) etiology often multifactorial in the elderly [7] Epidemiology: - 10-17% of community-dwelling elderly (>= 65 years) [8,14,17] - prevelance is 48% in skilled nursing facilities [9] Clinical manifestations: 1) symptoms a) fatigue b) exercise intolerance c) headache d) dizziness e) faintness f) exertional dyspnea g) angina pectoris h) palpitation i) claudication j) symptoms develop only when Hgb < 7 g/dL if anemia is chronic unless coexistent pulmonary or cardiovascular disease 2) signs a) hypotension b) tachycardia c) tachypnea d) jaundice e) pallor of nails & conjunctiva f) hepatosplenomegaly g) loss of proprioception & vibration sense (B12 deficiency) h) evidence of underlying disease as etiology of anemia Laboratory: 1) general a) complete blood count (CBC) with differential - Hgb < 13.5 g/dL (males), < 11.5 g/dL (females) - RBC count - < 5 x 10E12/L in Fe deficiency - > 5 x 10E12/L in thalassemia - RDW - > 16 in Fe deficiency - < 16 in thalassemia - mean corpuscular volume (MCV) classifies anemia as microcytic anemia, normacytic anemia, macrocytic anemia - mean corpuscular hemoglobin concentration (MCHC) to confirm hypochromic anemia b) reticulocyte count c) peripheral blood smear - hemolysis: spherocytes, schistocytes, blister cells, basophilic stippling d) iron studies - 33% of patients with iron deficiency anemia have a normal MCV [4] - serum iron - total iron-binding capacity (TIBC) - serum ferritin - < 10 ng/mL confirms iron deficiency - > 100 mg/l rules out iron deficiency even with inflammation [3] - transferrin saturation - measured by serum iron/total-iron binding capacity (TIBC) - <10% is consistent with iron deficiency [3] - >15% is consistent with anemia of chronic disease - 10-15% indicates a bone marrow biopsy to distinguish iron deficiency from anemia of chronic disease e) fecal occult blood f) direct antiglobulin test (Coomb's test), especially if spherocytes on peripheral smear g) low serum erythropoietin level may confirm hypoplastic marrow h) serum LDH is elevated in serum with hemolytic anemia & megalobastic anemia (non-specific) i) hemoglobin electrophoresis - target cells, sickle cells on peripheral smear - splenomegaly - evidence of bone remodelling - hemoglobinopathy - beta-thalassemia - hemoglobin A2 3-7% in beta-thalassemia minor - hemoglobin A2 7-90% in beta-thalassemia major j) lead in blood - basophilic stippling k) bone marrow biopsy & bone marrow aspiration if indicated - leukopenia - thrombocytopenia - myelocytes - nucleated erythrocytes - lymphadenopathy - splenomegaly 2) microcytic anemia a) iron studies (see above) b) fecal occult blood c) hemoglobin electrophoresis (see above) d) free erythrocyte (zinc) protoporphyrin (FEP) - increased in: - iron deficiency - anemia of chronic disease - heavy metal exposure - normal in: - thalassemia - sideroblastic anemia e) Heinz body prep f) lead in blood - basophilic stippling g) serum protein electrophoresis 3) normocytic anemia a) specific tests for underlying disorder based upon clinical findings b) serum creatinine (anemia of chronic renal failure) c) hemoglobin electrophoresis d) serology for Helicobacter pylori e) fecal occult blood f) thyroid function tests* 4) macrocytic anemia a) serum B12 b) serum folate c) serum copper d) thyroid function tests 5) see ARUP consult [5] * although other sources suggest hypothyroidism is associated with macrocytic anemia, ref [18] states hypothyroidism is a common cause of normocytic normochromic anemia Special laboratory: 1) upper GI endoscopy a) suspicion of upper GI bleed b) telangiectasias (hereditary hemorrhagic telangiectasias) [2] 2) colonoscopy for positive fecal occult blood Complications: - anemia in the very old is associated with increased mortality independent of comorbidites [6,11] - increased severity of anemia is a risk factor for hospitalization among residents of skilled nursing facilities [9] - in the elderly, anemia is a risk factor for - functional impairment - cognitive impairment [11,13,15] - decline in quality of life [15,16] Management: 1) treat underlying disorder 2) removal of toxic agent 3) avoid iatrogenic anemia - avoid blood tests unless they are clinically indicated 4) blood transfusion - delay elective surgery in patients who have correctable anemia until the anemia has been treated [18] - in critically ill patients with severe anemia, transfusion may be indicated even if fully matched erythrocytes are not available [3]

Interactions

disease interactions

Related

pharmaceutical agents associated with anemia

Useful

bone marrow biopsy complete blood count (CBC) direct antiglobulin test (DAT, direct Coomb's test) erythropoietin in serum fecal occult blood; fecal immunochemical testing; fecal immunofluorescence testing, multitarget stool DNA (mt-sDNA, FOB, FIT, iFOBT, ColonCARE, Hemoccult, ICT, InSure) ferritin in serum/plasma folate in serum/plasma Heinz body Helicobacter pylori hemoglobin electrophoresis iron (Fe+2/Fe+3) in serum iron-binding capacity in serum (TIBC) lactate dehydrogenase (LDH) in serum lead in blood peripheral blood smear protoporphyrin free in erythrocytes reticulocyte count thyroid function test

Specific

anemia in pregnancy; gestational anemia congenital dyserythropoietic anemia (CDA-II or HEM-PAS) hemolytic anemia HIV-associated anemia hypochromic anemia hypoplastic anemia macrocytic anemia microcytic anemia Plummer-Vinson; Patterson-Kelly syndrome; sideropenic dysphagia refractory anemia (RA) transient erythroblastopenia of childhood

General

erythrocyte disorder

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 572-74
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 409-415
  3. Schiller G, UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  4. Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 18. American College of Physicians, Philadelphia 2006, 2012, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. ARUP Consult: Anemia The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/anemia - ARUP Consult: Anemia Testing Algorithm https://arupconsult.com/algorithm/anemia-testing-algorithm
  6. den Elzen WP, Willems JM, Westendorp RG et al Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study. CMAJ. 2009 Aug 4;181(3-4):151-7 PMID: 19635749
  7. Patel KV1, Longo DL, Ershler WB et al Haemoglobin concentration and the risk of death in older adults: differences by race/ethnicity in the NHANES III follow-up. Br J Haematol. 2009 May;145(4):514-23 PMID: 19344387
  8. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  9. Artz AS, Fergusson D, Drinka PJ et al Prevalence of anemia in skilled-nursing home residents. Arch Gerontol Geriatr. 2004 Nov-Dec;39(3):201-6. PMID: 15381339
  10. Artz AS, Fergusson D, Drinka PJ et al Mechanisms of unexplained anemia in the nursing home. J Am Geriatr Soc. 2004 Mar;52(3):423-7. PMID: 14962159
  11. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006 Apr;119(4):327-34. PMID: 16564775
  12. Morley JE. Anemia in the nursing homes: a complex issue. J Am Med Dir Assoc. 2012 Mar;13(3):191-4. PMID: 22261540
  13. Deal JA, Carlson MC, Xue QL, Fried LP, Chaves PH. Anemia and 9-year domain-specific cognitive decline in community-dwelling older women: The Women's Health and Aging Study II. J Am Geriatr Soc. 2009 Sep;57(9):1604-11. PMID: 19682133
  14. Guralnik JM1, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004 Oct 15;104(8):2263-8. Epub 2004 Jul 6 PMID: 15238427
  15. Lucca U, Tettamanti M, Mosconi P et al Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the "Health and Anemia" study. PLoS One. 2008 Apr 2;3(4):e1920. PMID: 18382689
  16. Thein M, Ershler WB, Artz AS et al Diminished quality of life and physical function in community- dwelling elderly with anemia. Medicine (Baltimore). 2009 Mar;88(2):107-14. PMID: 19282701
  17. Stauder R, Valent P, Theurl I. Anemia at older age: Etiologies, clinical implications and management. Blood. 2017 Nov 15. pii: blood-2017-07-746446. PMID: 29141943 http://www.bloodjournal.org/content/early/2017/11/15/blood-2017-07-746446
  18. NEJM Knowledge+ Hematology - Erdogan M, Kosenli A, Ganidagli S, Kulaksizoglu M. Characteristics of anemia in subclinical and overt hypothyroid patients. Endocr J. 2012;59(3):213-20. PMID: 22200582 Free article.
  19. Cascio MJ, DeLoughery TG. Anemia: evaluation and diagnostic tests. Med Clin North Am. 2017;101:263-84. PMID: 28189170
  20. Choosing Wisely. July 23, 2018 Society for the Advancement of Blood Management. http://www.choosingwisely.org/societies/society-for-the-advancement-of-blood-management/
  21. Anemia: NIH Institute and Center Resources https://www.nhlbi.nih.gov/health-topics/anemia