approccio clinico al paziente geriatrico con anemia...distribution of the prevalence of anemia by...

Giovambattista DesideriUO Geriatria e Lungodegenza

Università degli Studi di L’Aquila

Approccio clinico al paziente geriatrico con anemia

Approccio clinico al paziente geriatrico con anemia

Frequente

Tettamanti M et al. Haematologica 2010;95(11):1849-1856.

Prevalence, incidence and types of mild anemia in the elderly:the “Health and Anemia” population-based study

Distribution of the prevalence of anemia by level in the elderly:the “Health and Anemia” population-based study

Tettamanti M et al. Haematologica 2010;95(11):1849-1856.

Mild anemia, Hb 10.0–11.9 g/dL in females and Hb 10.0–12.9 g/dL in males;

Moderate anemia, Hb 8.0–9.9 g/dL; Severe anemia, Hb< 8.0 g/dL.

Blanc B et al. World Health Organization; 1968.

Approccio clinico al paziente geriatrico con anemia

Frequente

Rilevante in chiave prognostica

Relationship between hemoglobin concentration and 5-year all-cause mortality in community-dwelling, disabled older women

Chaves PH et al. J Am Geriatr Soc. 2004; 52:1811–1816.

+20%

-25%D45%

Anemia in Old Age Is Associated With Increased Hospitalization

Penninx BW et al. J Gerontol A Biol Sci Med Sci2006;61:474–9.

<12 g/dL in women<13 g/dL in men

Relationship between the baseline levels of Hct and the cumulative incidence of ESRD

Iseki K et al. Kidney International (2007) 72, S4–S9

Kaplan-Meier survival function of time to dementiadiagnosis by baseline anemia

Hong CH et al. Neurology 2013;81:528–533

<12 g/dL in women<13 g/dL in men

Cahves PH et al. J Gerontol A Biol Sci Med Sci. 2005 Jun;60(6):729-35.

Cross-sectional relationship between Hb concentration and prevalentfrailty status, Women’s Health and Aging Studies I and II, 1992–1996.

Difference in event-free survival rates between iron-deficient and non–iron-deficient patients with HF with or without anemia

Klip IT et al. Am Heart J 2013;165:575-582

<12 g/dL in women<13 g/dL in men

ID commonly occurs even

without anaemia in HF

ID (with or without anaemia)

is present in 50% of HF

patients

Iron deficiency definition used:

− Serum ferritin <100 µg/L or

− Serum ferritin <299 µg/L if TSAT

<20%

Iron deficiency and/or anemia stratified by NYHA functional class.Prevalence of ID and/or anemia per NYHA functional class.

Klip IT et al. Am Heart J 2013;165:575-582

ID/A

ID

A

ANAEMIA

Tissue hypoxia

Peripheral vasodilation

Blood pressure

Sympathetic activity

Renal blood flow

Renin-angiotensin aldosterone ADH

Salt & Fluid retention

Plasma volume

Oedema

LVdiameter

LV remodelling Apoptosis Necrosis

Worsening

HF

Vicious circle of Anemia and HF

HF

Anand IS et al. J Am Coll Cardiol 2008;52:501–11

Swedberg K et al. N Engl J Med 2013;368:1210-9.

Treatment of Anemia with DarbepoetinAlfa in Systolic Heart Failure – RED HF study

Monthly Hemoglobin Levels through 60 MonthsAccording to Study Group

Impact of iron status on exercise capacity (6-minute walk test) in patients with chronic heart failure

Enjunaes C et al. Rev Esp Cardiol. 2016;69(3):247–255

Iron-dependent changes in cellular energy metabolism

Brown DA et al. Nat Rev Cardiol. 2017 April ; 14(4): 238–250.

The numbers of the heart:

100.800 beats/day

5-6 kg ATP/day

mitochondria: 40% cell volume

Bayeva M et al. J Am Coll Cardiol 2013;61:599–610

Recommendations for iron replacement in HF

2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of HF1

COR LOE

In patients with NYHA class II and III HF and iron deficiency (ferritin <100 ng/mL or 100 to 300 ng/mL if transferrin saturation is <20%), intravenous iron replacement might be reasonable to improve functional status and QoL.

NEW: New evidence consistent with therapeutic benefit.

IIb B-R

(3,4)

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure2

Class Level

Intravenous FCM should be considered in symptomatic patients (serum ferritin <100 μg/L, or ferritin between 100–299 μg/L and transferrin saturation <20%) in order to alleviate HF symptoms, and improve exercise capacity and quality of life.

IIa A

(3,4)

1Yancy CW et al. Circulation. 2017 Aug 8;136(6):e137-e1612Ponikowski P et al. European Heart Journal (2016) 37, 2129–2200

3Anker SD, et al. N Engl J Med 2009;361:2436–2448 FAIR-HF4Ponikowski P, et al. Eur Heart J 2015;36:657–668 CONFIRM

Anker SD et al. N Engl J Med 2009;361:2436-48.

FAIR-HF: primary endpoint: Self-Reported Patient Global

Assessment at Wk 24

459 pts with chronic HF - NYHA class II or III, LVEF <40% (for patients with NYHA class II or <45% for NYHA class III)

Iron deficiency (ferritin level <100 μg/L or between 100 and 299 μg/L, if the transferrinsaturation was <20%), and a hemoglobin levelof 95 to 135 g/L.

FAIR-HF: primary endpoint: NYHA Functional Class at Wk 24

FAIR-HF: primary endpoint: Self-Reported Patient Global Assessment and NYHA class at Wk 24 according to the presence or

absence of anaemia at baseline

Filippatos G et al. European Journal of Heart Failure (2013) 15, 1267–1276

Self-Reported Patient Global Assessment

Anker SD et al. N Engl J Med 2009;361:2436-48.

FAIR-HF: secondary endpoint: 6-Minute-Walk Test

Ponikowsky P et al. European Heart Journal (2015) 36, 657–668

CONFIRM-HF: 6-Min Walk Test Over Time

Ponikowsky P et al. European Heart Journal (2015) 36, 657–668

CONFIRM-HF: Patient Global Assessment and NYHA Functional Class over Time

Anker SD et al. Eur J Heart Fail. 2018 Jan;20(1):125-133.

Effects of FCM on CV hospitalisations and mortality rates iniron-deficient HF patients: an individual patient data meta-analysis

Anker SD et al. Eur J Heart Fail. 2018 Jan;20(1):125-133.

Effects of FCM on CV hospitalisations and mortality rates iniron-deficient HF patients: an individual patient data meta-analysis

Approccio clinico al paziente geriatrico con anemia

Frequente

Rilevante in chiave prognostica

Eterogenea nelle cause

Types of anemia and mild anemia in the elderly population

Tettamanti M et al. Haematologica 2010;95(11):1849-1856.

Main types of anemia in the elderly population

Causes of iron deficiency anemia

Zeller MP et al. CMAJ March 13, 2017 189 (10) E409; DOI: https://doi.org/10.1503/cmaj.160153

Oral anticoagulation among atrial fibrillation patients with anaemia: an observational cohort study

Bonde AN et al. European Heart Journal (2019) 0, 1–9

Mild anemia (MA): Hb 6.83–7.45 mmol/L for women and Hb 6.83–8.03 mmol/L formen)Moderate/severe anemia (MSA): Hb <6.83 mmol/L.

MSA 14% MA 20%

To convert mmol to mg: X 1/0.6206

Diagnostic Blood Loss From Phlebotomy and Hospital-Acquired Anemia During Acute Myocardial Infarction

Salisbury AC et al. Arch Intern Med. 2011 Oct 10;171(18):1646-53

Twelve-month mortality among patients with mild Hospital-AcquiredAnemia (HAA), moderate-severe HAA, and chronic anemia and AMI

Salisbury AC et al. Circ Cardiovasc Qual Outcomes. 2010;3:337-346

Michels K et al. PLoS Pathog. 2015 Aug; 11(8): e1004998

Anemia of chronic disease

Ganz T. Physiol Rev 93: 1721–1741, 2013DeLoughery TG. N Engl J Med 2014;371:1324-31.

Main types of anemia in the elderly population

Vitamin B12 and folate metabolism and function

Green R et al. Nat Rev Dis Primers. 2017 Jun 29;3:17040

The relationship between distribution of mean corpuscular volume (MCV), anisocytosis and red blood cell distribution width (RDW).

Danete E et al. J Thorac Dis 2015;7(10):E402-E411

Main types of anemia in the elderly population

Update on Anemia in ESRD and Earlier Stages of CKD

Fishbane S et al. Am J Kidney Dis. 71(3): 423-435. NEJM. 2017;376:1965-1971)

Main types of anemia in the elderly population

The origins of age-related proinflammatory state

Ferrucci L et al. Blood, 2005 105: 2294-2299

Serum erythropoietin (EPO) levels by hemoglobin concentration among irondeficiency anemia, unexplained anemia in the elderly, and myelodysplastic

syndromes and acute myeloid leukemia.

Arts AS et al. J Gerontol A Biol Sci Med Sci. 2011 August;66A(8):925–932

Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial

JAMA Intern Med. 2017 April 01; 177(4): 480–490.

788 elderlyTestosterone <275 ng/dL

16% with anemia 6.3% myelodysplasia, 33.3% iron deficiency, 2.4% B12 deficiency 7.9% chronic inflammation

or disease 49.2% unexplained anemia

Approccio clinico al paziente geriatrico con anemia

Frequente

Rilevante in chiave prognostica

Eterogenea nelle cause

….e la gestione?

Evaluation and Management of Anemia in the Elderly

Goodnought LT e al. Am J Hematol. 2014 January ; 89(1): 88–96 (modified)

Iron deficiency

Comparative efficacy of differentoral iron formulations for treating bleeding-induced

moderate-to-severe anemia.

Gómez-Ramírez S et al. Pharmaceuticals 2018, 11, 97; doi:10.3390/ph11040097

Ironpyrophosphate

Phospholipmembrane

SucresterenvelopeTricalcium

phosphate

Condizione Motivazione

INTOLLERANZA INTESTINALE Nausea, vomito, stipsi, diarrea

MANCATO ASSORBIMENTO

Gastrectomia, by-pass duodenale, chir. bariatrica,

HP, gastrite atrofica, celiachia

Forme genetiche (IRIDA)

Flogosi: IBD, CKD, Neoplasie, Età avanzata

Mancato incremento Hb dopo 4 settimane

ANEMIA GRAVE (Hb < 7-8 g/dL) Necessità di un rapido miglioramento

TRATTAMENTO CON EPO Inefficace la terapia orale

PERDITE EMATICHE CRONICHE

Polimenorrea

Teleangectasia emorragica ereditaria

Angiodisplasie

ALTRE

Programmazione di chirurgia maggiore entro 6 settimane

Insufficienza cardiaca sistolica cronica

Secondo e terzo trimestre di gravidanza

Indicazioni al trattamento parenterale

Toblli JE et al. Drug Design, Development and Therapy 2014:8 2475–2491

Optimizing iron delivery in the management of anemia: patient

considerations and the role of FCM

Evaluation and Management of Anemia in the Elderly

Goodnought LT e al. Am J Hematol. 2014 January ; 89(1): 88–96 (modified)

Iron deficiencyCKD

Approccio clinico al paziente geriatrico con anemia

Frequente

Rilevante in chiave prognostica

Eterogenea nelle cause

….e la gestione?

Approccio clinico al paziente geriatrico con anemia

Pensiamoci

Non trascuriamola

Interpretiamola

Trattiamola