PREVALENZA E DETERMINANTI DI

ANEMIA DA DISORDINE CRONICO IN

PAZIENTI ANZIANI OSPEDALIZZATI

AFFETTI DA BPCO

Piera Ranieri

UO Medicina, Istituto Clinico S.Anna, Brescia,

Gruppo di Ricerca Geriatrica, Brescia

SEMINARI DEL VENERDI’ DEL GRUPPO DI RICERCA GERIATRICA

Attualità nell’organizzazione dei servizi di geriatria

Brescia, 23 gennaio 2009

Selezione della popolazione di studio

Pazienti anziani ospedalizzati

(>65 anni)

n=811

Pazienti con diagnosi di BPCO

n=457 (56%)

Pazienti affetti da BPCO elegibili

per lo studio

n=386

Pazienti senza diagnosi di

BPCO

n=354

Pazienti affetti da malattie

severe o terminali

n=71

Pazienti affetti da

scompenso cardiaco

n=183

Popolazione di studio: pazienti

anziani affetti da BPCO

n=158

Pazienti con anemia micro e

macrocitica

n=45

ESCUSIONE

ESCUSIONE

Prevalenza di anemia:

53,5%

45,5% 48,0%

51,9%

61,1 %

52,9 50,2 51,9

0

20

40

60

80

Total population NO COPD patients COPD patients

Pre

va

len

ce o

f A

ne

mia

(%

)

12,2

12,212,1

Figure 2. Prevalence of anemia in study population and mean Hb value (mg/dl) for each study group

Anemia e BPCO

La prevalenza di anemia nella popolazione generale aumenta

con l’età. La cosiddetta condizione “ anemia da disordine

cronico”, è una ben nota comorbilità di numerose patologie

croniche

E’ stato ampiamento dimostrato che in tali patologie, quali

l’insuffiienza renale cronica, lo scompenso cardiaco,

l’infezione da HIV, l’infezione epatitica cronica HCV correlata

e le neoplasie, la presenza di anemia si associa a ridotta

qualità della vita, aumentata morbilità ed aumentata mortalità

La prevalenza di anemia aumenta ulteriormente nei pazienti

anziani ospedalizzati , associandosi ad elevata mortalità,

disabilità, declino delle performance funzionali e bassa qualità

della vita.

Anemia e BPCO Tra le malattie croniche, la BroncoPneumopatia Cronica

Ostrutiva (BPCO) è un’altra condizione clinica che

sembra sia associata significativamente alla presenza di

anemia, soprattutto se considerata nell’ambito dei già noti

effetti sistemici di questa patologia, che attualmente viene

considerata una malattia infiammatoria multisistemica.

La policitemia, tradizionalmente associata alla BPCO, si

verifica sempe meno frequentemente in relazione alla più

ampia diffusione dell’ossigeno-terapia ed alla più

rigorosa correzione dell’ipossiemia

Recenti studi suggeriscono che l’anemia è altamente

prevalente nei pazienti affetti da BPCO ed è associata ad

outcome negativi

Erythropoietic response to hypoxaemia in diffuse

idiopathic pulmonary fibrosis, as opposed to chronic

obstructive pulmonary disease.Tassipoulos S, Kontos A, Konstantopoulos K et al.

Resp Med 2001; 95(6):471-475

The aim of this study was to assess the erythropoietic response to hypoxaemia in patients with

diffuse idiopathic pulmonary fibrosis (DIPF), and to speculate on the underlying mechanisms.

Patients on an established chronic respiratory failure due to DIPF or chronic obstructive

pulmonary disease (COPD) were studied. The erythropoietic response to hypoxaemia in both

conditions was assessed. We studied 18 patients with DIPF and 29 patients with COPD in

respiratory failure in a stable stage, free from acute infection and congestive heart failure.

Blood gases, erythrocytic parameters, as well the serum levels of iron, ferritin and

erythropoietin were determined. All the DIPF patients studied, apart from two, had normal or

subnormal haematocrit values. The patients with COPD had an inconsistant response to

hypoxaemia; 12 had normal or subnormal haematocrit values and the remaining 17 were

erythraemic. The mean value of erythropoietin (EPO) in both DIPF and COPD patients was

significantly higher than normal. In conclusion, patients with DIPF exhibit a lack of

erythropoietic response to hypoxaemia, despite the augmented erythropoietin levels. This may

reflect a defective bone marrow erythropoietic response in DIPF patients. It is suggested that

the pathophysiology of DIPF underlies this mechanism.

BACKGROUND: Anemia in patients with COPD and its pathophysiology is an

understudied issue.

METHODS: In a group of 101 COPD patients (FEV(1) percentage of predicted, 37 +/-

2% [mean +/- SEM]; mean age, 61 +/- 1 years; 35% female gender), the prevalence of

anemia and its relationship to body mass and weight loss, inflammatory parameters, and

erythropoietin levels was determined. Data were compared to a control group (healthy

persons with matched age) in order to identify potential factors that may influence the

development of anemia in patients with COPD.

RESULTS: Anemia was diagnosed in 13 patients (hemoglobin levels < 13.5 mg/dL in

male patients and < 12.0 mg/dL in female patients), which represents a prevalence of

13%. Anemic COPD patients showed elevated erythropoietin levels (41.8 +/- 25.4 U/L

vs 16.3 +/- 2.9 U/L) and an increased inflammatory response compared to nonanemic

patients. A significant inverse correlation of hemoglobin vs erythropoietin (r = - 0.84, p <

0.01) was observed in anemic COPD patients, but not in the nonanemic group.

CONCLUSION: Anemic COPD patients show high erythropoietin levels, which may

indicate presence of erythropoietin resistance. The latter may be mediated through

inflammatory mechanisms, which is typical for anemia of chronic illness.

Anemia and inflammation in COPDJohn M, Hoering S, Doehner W, at al.

Chest 2005;127:825-29

Anaemia of chronic disease (ACD), with chronically low levels of circulating haemoglobin, is

an immune driven abnormality that occurs in many inflammatory diseases, and also in

chronic heart failure. Although chronic obstructive pulmonary disease (COPD) is

"traditionally" associated with polycythaemia, the systemic inflammation that is now

recognised as a feature of COPD makes it a possible cause of ACD. If present in COPD,

anaemia could worsen dyspnoea and limit exercise tolerance. Preliminary evidence

suggests that anaemia in COPD patients may be more prevalent than expected, concerning

10-15% of patients suffering from severe forms of the disease. A database study conducted

in 2,524 COPD patients being prescribed long-term oxygen therapy has shown that a low

haematocrit is a strong predictor of survival in this population, before body mass index, and

is associated with more hospitalisations and a longer cumulative duration of hospitalisation.

COPD patients with low haemoglobin levels have a poorer prognosis than COPD patients

with normal haemoglobin levels in the event of acute gastrointestinal bleeding or after

elective aneurysm repair. Raising haemoglobinaemia through transfusion decreases minute

ventilation and work of breathing in COPD patients. These preliminary evidences point to the

need to study the prevalence of anaemia, and its physiological and clinical impact in chronic

obstructive pulmonary disease. When this body of knowledge is available, the question of

the putative benefits of raising haemoglobinaemia in chronic obstructive pulmonary disease

will have to be addressed.

The potential impact of anemia of chronic

disease in COPDSimilowski T, Agusti A, and Schonhofer B.

Eur Respir J. .2006;27:390-396

Haemoglobin level and its clinical impact in a cohort

of patients with COPDCote C, Zilberberg MD, Dordelly SH, and Celli B.

Eur Respir J. 2007;29:923-929.

Haemoglobin (Hb) abnormalities in chronic obstructive pulmonary disease (COPD) are

not well characterised. The present authors investigated the prevalence and association

of abnormal Hb with clinical outcomes. Analysis of a prospective cohort of stable COPD

outpatients (n = 683) in a USA Veterans Administration pulmonary clinic was

undertaken. Patients were classified as anaemic (Hb <13 g.dL(-1)), polycythemic (Hb >

or =17 g.dL(-1) and > or =15 g.dL(-1) for males and females, respectively) or normal.

Demographic characteristics and physiological/functional outcomes were compared

between groups. Regression models adjusting for confounders examined the

independent association of anaemia with clinical outcomes. Anaemia was present in 116

(17%) patients and polycythemia in 40 (6%). While the only values that differed between

polycythemic and nonpolycythemic patients were mean body mass index and Hb,

anaemic patients showed a significantly higher modified Medical Research Council

dyspnoea scale score (2.8 versus 2.6), lower 6-min walk distance (265 versus 325 m)

and shorter median survival (49 versus 74 months) than nonanaemic patients. In

regression models, anaemia independently predicted dyspnoea and reduced exercise

capacity. Anaemia in chronic obstructive pulmonary disease was an independent risk

factor for reduced functional capacity. Polycythemia prevalence was low and had no

association with worsened outcomes. Further work is required to evaluate the effect of

anaemia correction on outcomes in chronic obstructive pulmonary disease.

Pazienti e Metodi

811 pazienti ultra65enni (f = 61,7%; età media

80,1±7.5anni) consecutivamente ammessi in un reparto

di Medicina per acuti durante un periodo di 12 mesi.

Sono state valutate:

• funzioni cognitive (Mini Mental State Examination-MMSE)

• funzioni affettve (Geriatric Depression Scale-GDS 15 items))

• comorbilità (Charlson Index score)

• severità della pre-esistente ostruzione bronchiale (FEV1

%pred)

• gravità della patologia acuta (APACHE II score)

• indicatori nutrizionali e di fragilità (BMI, colesterolo ed

albumina serica)

• indicatori di infiammazione (VES e PCR)

• stato funzionale (IADL e Barthel Index pre-morboso,

all’ammissione ed alla dimissione)

Diagnosi di Anemia

L’ANEMIA è stata definita secondo I criteri

della World Health Organization (WHO):

Hb <12 d/dL nelle donne

Hb <13 g/dL negli uomini

Table 1. Characteristics of COPD study

population stratified for the presence of anemia

VARIABLES NO ANEMIA

(N=76)

ANEMIA

(N=82)

p

Age (years) 78.4±7.6 82.4±6.1 ,000

Age >80 years 37 71 ,000

Gender (Male) 29 59 ,000

Body Mass Index (Kg/m2) 24.3±4.4 24.2±4.6 n.s.

Smoking

Never 59 47 n.s.

Former 25 44 ,04

Current 16 9 n.s.

Mini Mental State Examination 22.6±5.4 20.7±6.5 ,056

Dementia (MMSE<18/30) 19 28 n.s.

Geriatric Depression Scale 4.7±3.2 4.7±3.0 n.s.

FEV1 (% of pred.) 82.5±8.3 58.6±7.8 ,05

FEV1 <60 % of pred. 37 75 ,05

Instrumental Activities of Daily Living (f. lost) 3.2±3.0 3.8±2.9 n.s.

Table 1. Characteristics of study population

stratified for the presence of anemia.

VARIABLES NO ANEMIA

(N=76)

ANEMIA

(N=82)

p

Barthel index (BI) pre-admission 83.4±26.5 73.5±28.5 ,026

Functional disability pre-admission (BI<60) 16 33 ,011

Barthel index at admission 67.3±33.8 51.6±35.4 ,005

Functional disability at admission (BI<60) 36 58 ,004

Barthel index at discharge 76.7±29.4 67.4±31.0 ,05

Functional disability at discharge (BI<60) 24 38 ,05

Apache II score 7.8±3.1 8.9±3.9 ,05

Charlson Index (CI) 3.4±1.5 4.1±1.8 ,009

High comorbidity (Charlson Index >3) 49 60 n.s.

Serum cholesterol (mg/dl) 188.2±46.3 171.8±42.1 ,021

Hypocholesterolemia (<140 mg/dl) 10 23 ,02

Serum albumin (mg/dl) 3.5±0.5 3.4±0.5 n.s.

Hypoalbuminemia (<3.4 mg/dl) 38 57 ,01

CRP (mg/dl) 45.4±52.0 49.6±46.0 n.s.

High CRP (>10 mg/dl) 56 77 ,005

Urea (mg/dl) 50.4±32.8 60.6±29.7 ,042

Creatinine(mg/dl) 1.15±0.9 1.29±0.6 n.s.

Renal Insufficiency (creatinine>1,3 mg/dl)

Table 3. Multiple Logistic Regression Analysis for

association between Anemia and clinical variable*

Variables B S.E. Exp (B) p

Age (>80 years) 1,77 0,43 5,9 ,000

Gender (male) -1,35 0,42 0,2 ,001

CRP (>10 mg/dl) 1,12 0,53 3,1 ,03

Renal insufficiency 1,07 ,503 2,9 ,03

*Adjusted for: severity of bronchial obstruction, pre-morbid functional disability, funcyional disability at hospital admission and at discharge, hypoalbuminemia, severity of acute ilness, ischemic heart disease and neoplastic disease.

Kaplain-Meier curves stratified for anemia

INT MOR

2001000

Cu

m S

urv

iva

l

1,02

1,00

,98

,96

,94

,92

,90

,88

,86

,84

NON

ANEMIC

ANEMIC

P=0,02