Anemia in the elderly. Nattiya Teawtrakul MD., PhD

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Anemia in the elderly Nattiya Teawtrakul MD., PhD

Contents Definition of anemia in the elderly The impact of anemia in the elderly Etiology of anemia in the elderly Management of anemia in the elderly

Case Study A 75-year-old man was evaluted due to anemia

History Multiple comorbidities: Type 2 diabetes mellitus CKD stage 2 (GFR = 60 ml/min) Previous myocardial infarction (5 yrs ago) Post-ischemic chronic heart failure (EF=40%) with history of multiple hospital admissions

History Current medications: Aspirin 100 mg/day Omeprazole 20 mg/day Metformin 1000 mg/day Carvedilol 2.5 mg/day Furosemide 40 mg/day Enalapril 5 mg/day

Physical Exam HEENT: mildly pale conjunctivae, anicteric sclerae, no lymphadenopathy Heart & Lungs: within normal limit Abdomen: no hepatosplenomegaly Ext: no pitting edema, no leg ulcer

Laboratory Complete blood count: Hb 10.5 g/dl, Hct 32%, WBC 8,350 (PMN 65%, L35%), Platelet 225,000 MCV 85 fl, RDW 14.5% Blood smear: Normochromic normocytic anemia, no dysplastic changes Reticulocyte count: 1.1% BUN 13 mg/dl Creatinine 1.0 mg/dl (estimate GFR = 60.5 ml/min) Liver function test: within normal limit

1 Definition of anemia in the elderly The different Hb thresholds proposed?

Defining anemia in the elderly Proposer Males Females Pros Cons WHO 13 12 - Widely adopted - Developed in 1968 - Not include subjects > 65 years Beutler et al 13.2 (C) 12.7 (A) 12.2 (C) 11.5 (A) - Based on large database Culleton et al 13.7-14 12.6-13 - Based on associations of hard outcomes - Definition of healthy elderly based only on lab parameters - Relatively high thresholds - Association with outcomes does not proof casuality Andres et al 12 12 - Generally accepted by geriatricians - Not accounting for heterogeneity of health status Girelli D et al. Hemasphere 2018;2:1. http://dx.doi.org/10.1097/hs9.0000000000000040.

Defining anemia in the elderly The WHO is launching a program that should revise the Hb thresholds for defining anemia in different populations

Different hemoglobin thresholds proposed for defining anemia in the elderly, await for more precise definition in the future

2 The impact of anemia in the elderly Is it the same as younger adults?

Mortality risk per Hb level Culleton BF et al. Blood 2006;107:3841-46.

3 Etiology of anemia in the elderly Is it the same as younger adults?

Etiology Unexplained anemia Stanely L et al. Curr Opin Hematol 2012;19:133-40.

Etiology Girelli D et al. Hemasphere 2018;2:1. http://dx.doi.org/10.1097/hs9.0000000000000040.

Unexplained Anemia in the elderly

Aging Hematopoiesis

Altered EPO homeostasis Serum Epo levels and causes of anemia in the elderly Artz A et al. J Gerontol A Biol Sci Med Sci. 2011;66A(8):925-32.

Altered EPO homeostasis

Altered EPO homeostasis Anemia of unknown etiology VS. IDA EPO level in patient with unexplained anemia is lower than IDA

Altered EPO homeostasis Anemia of unknown etiology VS. ACD EPO level in patient with unexplained anemia is lower than ACD

Altered EPO homeostasis Anemia of unknown etiology VS. CKD EPO level in patient with unexplained anemia is higher than CKD

Altered EPO homeostasis

Hormonal dysregulation in the elderly

Hormonal dysregulation in the elderly

Androgen deficiency Testosterone deficiency in older men results in (mild) anemia Correcting the testosterone deficiency is associated with increased Hb levels

Unrecognized iron deficiency in the elderly Busti et al. Frontiers in pharmacology 2014; 5: 1-9.

MCV and iron deficiency in the elderly The elderly patients with absolute iron deficiency Microcytic anemia was found in 26.9% Normocytic anemia was found in 68.9% Macrocytic anemia was found in 4.2% Bach V et al. Clinical Interventions in Aging 2014; 9: 1187 1196

Serum ferritin and iron deficiency in the elderly

Serum ferritin and iron deficiency in the elderly Serum ferritin is not an appropriate test for the diagnosis of IDA in the elderly The serum ferritin cutoff level of 100 ng/ml can predict half of the patients with absolute IDA Babaei M et al. Res Bras Hematol Hemoter 2017; 39(3): 223-228.

Serum ferritin in elderly patients with iron deficiency is higher than younger patients and microcytosis often absent

Girelli D et al. Hemasphere 2018;2:1. http://dx.doi.org/10.1097/hs9.0000000000000040.

Back to the case Serum ferritin = 40 ng/ml Transferrin saturation = 15% The patient received iron supplement Evaluate the risk of GI malignancy Correction of anemia improve the clinical of congestive heart failure

3 Management of anemia in the elderly

Practical approach Always useful History and physical exam CBC/diff/plt, reticulocyte count, blood smear Tests of iron stores (Fe/TIBC, ferritin, soluble transferrin receptor) Tests of B12 deficiency; serum levels of cobalamin, methylmalonic acid, and serum homocysteine Chemistry panel: (CrCl) Serum erythropoietin Sometime Useful TSH, serum testosterone Tests of inflammation ( e.g. ESR, C reactive protein) Bone marrow aspiration and biopsy, cytogenetics RBC or serum folate level Specialized tests of erythrocyte physiology (e.g., RBC mass determination, serum interleukin-6 determination) Guralnik JM et al. ASH Education Book 2005.528-32.

Treatment options Folic acid and vitamin B12 Iron supplement Erythropoietin (Hb threshold of 11.5 g/dl) Androgen supplement (low testosterone)

Conclusions Anemia is a risk factor associated with morbidity and death in the elderly The pathogenesis of anemia in older adults is likely to be multifactorial Iron deficiency is common in the elderly and diagnostic criterion should be reconsidered

Thank you for your attention Any questions?