New concepts in diagnosis and management of iron deficiency

New concepts in diagnosis and
management of iron deficiency
Dr Jane KEIDAN
With thanks to
Vifor Pharma UK Ltd Rachael de Nobrega · Medical Advisor
Claire Atterbury
Mr Toby Richards
Outline
• Iron metabolism
• Treatment options
• Clinical use of intravenous iron-current and
developing areas
Total body iron: 2.5-4 grams
Mostly within the cardiovascular system, liver and muscles1:
Red blood cells
1.8 g
RES macrophages
0.6 g
Liver
1.0 g
Bone marrow
0.3 g
Muscles (myoglobin)
0.3 g
Other tissues
0.1 g
Bound to transport protein
Transferrin
0.003 g
Each ml of blood contains approximately 0.5 mg of iron
1. Hentze MW et al. Cell. 2004;117:285-97
Iron content of a balanced diet
• A balanced diet contains
5-6 mg of iron/1,000 kcal
• Recommended amount
of iron
– Adult man:
5-10 mg / day
– Adult woman:
7-20 mg / day
Iron in diet
• Richest sources of heme iron -lean meat , seafood.
Dietary sources of nonheme iron - nuts, beans,
vegetables, and fortified grain products.
• Heme iron has higher bioavailability than nonheme ironbioavailability 14- 18% from mixed diets that include
substantial amounts of meat/fish and 5% to 12% from
vegetarian diets
• Vitamin C enhances the bioavailability of nonheme iron
• Meat, poultry, and fish enhance nonheme iron
absorption, whereas phytate (present in grains and beans)
and certain polyphenols in some non-animal foods (such
as cereals and legumes) inhibit absorption
Prevalence of iron deficiency anaemia
1990-19951
Countries
Industrialised (%)
Developing (%)
Children (0-4 years)
20.1
39.0
Children (5-14 years)
5.9
48.1
Pregnant women
22.7
52.0
Women in
reproductive age
10.3
42.3
4.3
30.0
12.0
45.2
Men (15-59 years)
Seniors
1. World Health Organisation 2001. Iron Deficiency: Assessment, Prevention and Control.
Symptoms of iron deficiency with
or without anaemia
• Shortness of breath
• Fatigue
• Reduced physical performance and
endurance
• Decreased concentration span
• Reduced vitality
• Increased susceptibility for
infections
• Pale skin colour, hair loss and brittle
nails
Non-haematological benefits of iron1
•
•
•
•
•
Physical performance
Thermoregulation
Cognitive function
Restless legs syndrome
Immune function
1. Agarwal R. Am J Neph 2007;27:565-571
Normal Situation
Iron Cycle (Hb 14g/dl)
Iron status without inflammation1
Stage 1
Stage 2
Normal
Iron deficiency
Iron deficiency
anaemia
Ferritin (µg/l)
100±60
< 25
< 10
Transferrin saturation (%)
35±15
< 30
< 10
Normal (12-13)
Normal (12-13)
Low (< 12-13)
Storage iron
Transport iron
Erythron iron
Haemoglobin (g/dl)
1 Adapted from Crichton RR et al. Iron Therapy With a Special Emphasis on
Intravenous Administration (4th edition). UNI-MED Verlag AG, Bremen, Germany, 2008
Iron status with inflammation1
Inflammation
Normal
Iron depletion
Absolute
Functional iron
iron deficiency
deficiency
Storage iron
Transport iron
Erythron iron
Ferritin (µg/l)
100±60
< 25
< 10
>100
Transferrin saturation (%)
35±15
< 30
< 10
<20
Haemoglobin (g/dl)
Normal
Normal
Low
Low
1 Adapted from Crichton RR et al. Iron Therapy With a Special Emphasis on
Intravenous Administration (4th edition). UNI-MED Verlag AG, Bremen, Germany, 2008
HEPCIDIN and FERROPORTIN
•
•
•
•
•
Hepcidin is a hormone produced by the liver
Discovered in 2000
Pivotal in iron metabolism, principle regulator
Inhibits iron transport across cell membranes via ferroportin
In gut prevents iron absorption by blocking iron release from
enterocytes
• In macrophages prevents stored iron release to marrow
• Hepcidin production inhibited by iron deficiency-increased
absorption and release of iron from stores
• Hepcidin production stimulated by inflammation- poor
absorption and iron trapped in stores
Absolute & functional iron deficiency
Absolute
iron
deficiency
 Depleted body iron stores
– Low serum ferritin (<100ng/ml) or
– TSAT <20%
– Low hepcidin
 Inadequate iron supply to meet
Functional
iron
deficiency
demand despite normal or abundant
iron stores
– Normal or high ferritin levels
– TSAT <20%
– High hepcidin
ESA, erythropoiesis stimulating agent; TSAT, transferrin saturation
Wish JB. Clin J Am Soc Nephrol 2006;1:S4-8
Iron replacement strategies
•
•
•
•
Dietary iron
Oral iron
Parenteral iron
Blood transfusion
Oral iron therapy
• Advantages
: cheap
: easy to administer
• Disadvantages
:poorly absorbed(max 5-10 mg/day)
:GI side-effects common
:compliance often poor
:absorption limited if ferritin elevated
:absorption reduced in inflammation
Limitations of oral iron therapies1,2
Impaired intestinal
iron absorption
 Concomitant food or medication (e.g. phosphate binders, H2
blockers, proton pump inhibitors) – by raising the pH non-haem
foods cannot be absorbed
 Exacerbated by elevated hepcidin and other
inflammatory cytokine levels in conditions where there is
an inflammatory component
May be inadequate  Accelerated erythropoiesis can increase demand for iron
during ESA therapy
beyond the amount supplied orally
Gastrointestinal
adverse events
Compliance
Oxidative stress
 Can affect over 50% of patients
 Can adversely affect nutritional intake
 Improved if iron tablets are taken with food, but this
decreases absorption
 Pill burden: usually 2 or 3 tablets per day
 Affected by gastrointestinal intolerance
 High oral iron doses can saturate the iron transport
system if the iron is rapidly released, resulting in
oxidative stress
1. Macdougall IC. Curr Med Res Opin 2010;26:473–83;
2. Crichton RR et al. Iron Therapy With a Special Emphasis on Intravenous Administration (4th edition). UNI-MED Verlag AG, Bremen, Germany, 2008
Parenteral iron in UK
•
•
•
•
•
•
•
60 years
HMW Iron dextran (Imferon from Fisons)
Iron sucrose (Venofer) 1998
LMW Iron dextran (Cosmofer) 2001
Ferric carboxymaltose (Ferinject) 2008
Iron isomaltoside 1000 (Monofer) 2010
Ferumoxytol (Rienso) 2012
Use of intravenous iron
• Indicated for treatment of iron deficiency when oral
iron preparations are ineffective or cannot be used.
• Comparative clinical trials show a faster and more
prolonged response with IV iron than with oral iron.
• IV iron is more effective, better tolerated and
improves QoL to a greater extent than oral iron.
• Concerns regarding allergic reactions.
1. British National Formulary (BNF)
2. Gasche C et al. Inflamm Bowel Dis 2007;13:1545–53
Blood Transfusion
BCSH Guidelines for Clinical Use of Red Cell
Transfusions (2001)
• INDICATED where Hb level < 7g/dl
• NOT INDICATED where Hb level > 10g/dl
• UNCLEAR where Hb level is 7-10g/dl
– Symptomatic
– Inability to compensate
Blood transfusion
• Cost £122/unit plus admin costs
• Supply limitations
• Risks unique to transfusion
Risks associated with transfusion
Category
Risk per components issued
Total risk of death
1 in 125,000
Total risk of major morbidity
1 in 19,157
Risk of death from error
1 in 454,545
Risk of major morbidity from error
1 in 196,078
Risk of death from TACO
1 in 227,273
Risk of major morbidity from TACO
1 in 81,3000
Risk of major morbidity from ATR
1 in 36,764
Category
Risk of infected donation
entering blood supply
HBV
1 in 1.3 million
HCV
1 in 28.6 million
HIV
1 in 7.1 million
Copyright SHOT July 2014
SHOT Cumulative data: 17 years n=13141
Cumulative to 2012
2013
Unclassifiable complications of transfusion
Post-transfusion purpura
Transfusion-transmitted infection
Transfusion reactions which may not be
preventable
Transfusion-associated dyspnoea
Cell salvage and autologous transfusion
Acute transfusion reaction
Transfusion-associated graft vs host disease
Alloimmunisation
Transfusion-associated circulatory overload
Possibly or probably preventable by
improved practice and monitoring
Transfusion-related acute lung injury
Haemolytic transfusion reaction
Avoidable, delayed or undertransfusion
Anti-D immunoglobulin errors
Adverse events due
to mistakes
Handling and storage errors
Incorrect blood component transfused
0
500
1000
1500
Copyright SHOT July 2014
2000
2500
3000
3500
4000
Summary of treatment options
Disadvantages
Advantage
Oral iron
IV iron
Blood transfusion
Cost1
High iron content
Essential in cases of cardiovascular
instability1
Non-invasive
100% bioavailable
Replaces RBCs
Simple administration1
Compliance
Compliance
Convenient 2
Fast acting5
Well tolerated2
Malabsorption in inflammatory conditions3
Potential adverse
reactions
Potential transfusion reactions6,7
Intolerance3
Invasive
Invasive
Potential poor compliance3
Day case / inpatient
Day case / inpatient
Slower to increase haemoglobin vs IV iron4
Cost
Cost8
Interactions with many common oral drugs4
Limited supply7
Can delay investigative procedures, i.e.
colonoscopies
Increased risk of morbidity and mortality in
patients with cardiac disease7
Can only absorb 10-20mg a day
May worsen outcomes in acute bleeds and
surgical cases9
Complex administration7
1. Goddard AF et al. Gut 2011;60:1309e1316
2. Gasche C et al Inflamm Bowel Dis 2007;13(12):1545-53
3. Macdougall IC. Curr Med Res Opin 2010;26(2):473-482
4. Crichton R et al. Iron Therapy With Special Emphasis on
Intravenous Administration. UNI-MED Verlag AG 2008
5. Kulnigg S et al. Am J Gastroenterol 2007;102:1-11
6. Marik PE & Corwin HL. Crit Care Med 2008;36(11):3080-308
7. Knowles S Transfus Altern Transfus Med 2007;9(S2)2-9
8 Vifor Pharma UK Data on File
9. Restellini S et al. Aliment Pharmacol Ther 2013;37:316-322
Clinical use of intravenous iron
• Chronic kidney disease (dialysis and non-dialysis)
• Antenatal and postpartum
• Gastroenterology
– Inflammatory (Crohn’s & colitis), acute/chronic blood loss
•
•
•
•
Pre- and post-operatively
Oncology
Chronic Heart Failure
ITU, care of the elderly, palliative care (not covered
further)
NEPHROLOGY
Renal medicine
• Erythropoeitin (ESA) licensed in 1989
• Intravenous iron improves Hb responses and
reduces ESA requirements-overcomes
iron“supply” issue
• Approved by NICE
NICE Guidelines for Anaemia
Management in CKD
• Recommendation:
‘In non-dialysis patient with anaemia of
CKD in whom there is evidence of
absolute or functional iron
deficiency, this should be corrected
before deciding whether ESA
therapy is necessary.’
NICE 2011 Anaemia management in people with chronic kidney disease (CG114)
NICE Guideline 114
• Management of anaemia should be considered in people with anaemia of
chronic kidney disease (CKD) when the haemoglobin level is less than or
equal to 11.0g/dl.
• Patients receiving ESA maintenance therapy should be given iron
supplements to keep ferritin between 200-500µg/l & TSAT >20% or %HRC
<6%.
• In practice it is likely this will require intravenous iron.
Table 3.1 Test for functional iron deficiency with ferritin and TSAT or ferritin and %HRC
Ferritin
Tsat%
MCV
%HRC
Functional iron deficiency
>100µg/l
<20
Normal range
>6
Absolute iron deficiency
<100µg/l
<20
Low
>6
TSAT = transferrin saturation; MCV = mean corpuscular volume; HRC = hypochromic red cells
NICE 2011 Anaemia management in people with chronic kidney disease (CG114)
OBSTETRICS & GYNAECOLOGY
Risk factors for iron deficiency
in pregnant women 1
•
•
•
•
•
•
•
•
Ethnicity
Educational level/social class
Diet
Multiparity
Obesity
Anaemia during pregnancy
Total blood loss at delivery > 0.5L
Not exclusively breastfeeding
© www.pixelio.de
1. Bodnar LM et al. Am J Epidemiol. 2002;156:903-12
Adverse effects of iron deficiency in
pregnancy, at delivery and post partummaternal
• Unpleasant symptoms
– Lethargy, dyspnoea, fatigue, insomnia, light headedness,
dizziness and disorientation
• Increased susceptibility to infection
• Decrease in thermoregulation
• Ante partum haemorrhage ++
• Post partum haemorrhage ++
• Delayed wound healing
• Reduced quality and quantity of lactation or even halted
• Excessive fatigue and failure to cope
And for the fetus/baby……….
•
•
•
•
•
•
•
•
Poor uterine growth
Decreased liquor
Asymmetrical growth patterns
Small for dates
Premature delivery
Low birth weight
Failure to thrive (poor lactation)
And if it continues - poor concentration and reduced scholarly
achievements (Source SMA)
Antenatal iron deficiency anaemia
• Very common
• Estimated requirements of ~800 mgs extra iron over
the course of one pregnancy
• Detection poor
• Detection late
Iron deficiency anaemia becomes more
prevalent as pregnancy progresses
Percentage of women
First trimester
Second trimester
Third trimester
Anaemia*
Iron deficiency anaemia**
* Hb <11 g/dL in trimester 1, Hb <10.5 g/dL in trimester 2, Hb <11 g/dL in trimester 3
** Anaemia with serum ferritin <12 ng/mL
Scholl TO. Am J Clin Nutr. 2005;81:1218S-1222S
Iron therapy in pregnancy
• Oral iron works well if started early but can be
poorly tolerated
• Intravenous irons are contraindicated in the
first trimester – use must be confined to 2nd
and 3rd trimesters if benefits outweigh the
risks.
The Pregnancy Time Line Potential for Fe Therapy in Pregnancy
®
Venofer
Potential (%)
100
IV Iron Sucrose
Conception
1st trimester
0
-12
-4
Birth
2nd Trimeseter
3rd Trimester
4
12
18
24(PP)
32
40
48
Syner-Med
Ltd
Weeks
Oral Fe
Venofer
Post partum iron deficiency
• Lethargy, dyspnoea, fatigue, insomnia, light
headedness, dizziness and disorientation
• Increased susceptibility to infection
• Post partum haemorrhage ++
• Delayed wound healing
• Reduced quality and quantity of lactation or even
halted
• Excessive fatigue and failure to cope
• 44 women with haemoglobin (Hb) of <9 g/dl and ferritin of
<15 microgram/l at 24–48 hours post delivery.
• Oral ferrous sulphate 200 mg twice daily for 6 weeks or
200mg iron sucrose x 2
• Women treated with intravenous iron had significantly higher
Hb levels on days 5 and 14 (P < 0.01) than those treated with
oral iron
• Conclusion: Intravenous iron sucrose increases the Hb level
more rapidly than oral ferrous sulphate in women with
postpartum IDA
Bhandal N, Russell R. BJOG 2006;113:1248-1252
Oral iron vs IV iron in the postpartum
Bhandal N, Russell R. BJOG 2006;113:1248-1252
The King’s Lynn experience
Midwife-led service for prevention/management of anaemia in
pregnancy and reduction of transfusion exposure
Background
• We began to promote the use of intravenous iron in place of
blood transfusion having noted that some women who
received blood in pregnancy or post partum were iron
deficient.
OTHER DRIVERS FOR CHANGE
• Anaemia contributes to adverse outcomes for both mother
and baby.
• Transfusion avoidance is a national UK priority
Data from King’s Lynn
Units used vs number of women transfused
How did we achieve this?
•
•
•
•
Regular interdepartmental meetings
Midwife education days
Creating “champions”
Designing clear algorithms to empower the midwives to
appropriately diagnose and manage anaemia in pregnancy to
reduce transfusion rates and rationalise use of intravenous
iron.
• Providing easy access to haematology advice
• Dietary information emphasised to expectant mothers
It starts at booking………
• A careful history
–
–
–
–
–
General health
Dietary history
Family history
Bleeding history – Obstetric and otherwise
Any previous history of anaemia?
• Beliefs and wishes and fears concerning blood transfusion
• Drug history
• Allergies esp iron
Flow Chart 1a – Anaemia at Booking
Hb less than 11 g/dl at booking
(or less than 10.5 if above 12
weeks gestation) = ANAEMIA
MCV below 81fl
See Flow Chart 1b
MCV 81-99
See Flow Chart 1c
MCV above 99
See Flow Chart 1d
Flow Chart 1b – Anaemia
at Booking and MCV less
than 81
Hb less than 11 g/dl at booking (or less
than 10.5 if above 12 weeks gestation)
= ANAEMIA
AND
MCV less than 81fl
Check Haemoglobinopathy Screen
Thalassemia Trait
Check Ferritin
Normal
No action
Normal
Low
Dietary advice and Oral
Iron
Re-check Hb in 2 weeks
Unable to tolerate oral iron or failure
to show rise in Hb after 2 weeks
oral iron
Check Ferritin
(if not previously done)
Ferritin below 30
Ferritin above 30
Consider intravenous
iron in second
trimester
Re-check Hb in 4
weeks after IV Iron
No response
Seek Haematology
Advice
Danger of overuse of
intravenous iron
REMEMBER many women can be easily (and
cheaply) treated with oral iron if their anaemia
is detected and managed early in pregnancy.
Iron Therapy Timeline in O&G
The Pregnancy Time Line Potential for Fe Therapy in Pregnancy
Potential (%)
100
Conception
Oral Fe
Venofer
Birth
1st trimester
2nd Trimeseter
3rd Trimester
0
-12
-4
4
12
18
Weeks
24
32
40
48
Another chance at 28 weeks
• Review blood results and ACT ON THEM
Iron Therapy Timeline in O&G
The Pregnancy Time Line Potential for Fe Therapy in Pregnancy
Potential (%)
100
Conception
Oral Fe
Venofer
Birth
1st trimester
2nd Trimeseter
3rd Trimester
0
-12
-4
4
12
18
Weeks
24
32
40
48
Conclusions
• Collaboration between laboratory and midwifery staff has
improved care of pregnant women by early identification and
appropriate treatment of anaemia, reducing pregnancy-related
transfusion rates.
• For laboratory staff, the project delivers on the UK national
priority of transfusion avoidance, and has promoted dialogue
across the clinical –laboratory interface.
• For the midwives, the project has empowered them to
independently diagnose and manage anaemia in pregnancy
• For the mothers and babies, reduction in antenatal and postnatal
anaemia is known to improve outcomes.
PLUS
• If applied nationally, this approach would save blood AND
increase the blood donor pool
GASTROENTEROLOGY
British Society of Gastroenterology
Guidelines for the management of iron deficiency anaemia 2011
Definition of
anaemia
Iron deficiency*
Acknowledge WHO
cut-offs:
Men Hb <13g/dl
Women Hb <12g/dl
Low ferritin (cut-off varies
between 12-15 µg/l in absence
of inflammation).
Treatment
All patients should have iron
supplementation to correct
anaemia & replenish body
stores.
Low TSAT.
Suggest cut-off for
diagnosis of anaemia
should be the lower
limit of the normal
range as defined by
laboratory doing thr
test.
Low iron.
Trial of oral or parenteral iron
can help distinguish true iron
deficiency.
Raised TIBC.
Raised red cell zinc
protoporphyrin.
Raised serum transferrin
receptor.
Reticulocyte Hb content or %
hypochromic red cells for
diagnosis & monitoring of
functional ID.
For those intolerant or not
responding to oral iron
parenteral iron preparations can
be used.
Blood transfusions only for
patient with symptomatic
anaemia despite iron therapy or
those at risk of cardiovascular
instability. Iron treatment should
follow transfusion to replenish
stores.
* Values unspecified in guidelines
Guidelines on the Diagnosis and Management
of Iron Deficiency and Anaemia in IBD
(Gasche et al, 2007)
Treatment of Anaemia in IBD:
Iron Supplementation
• The preferred route of iron supplementation
in IBD is intravenous, even though many
patients will respond to oral iron. Intravenous
iron is more effective, better tolerated, and
improves the quality of life to a greater extent
than oral iron supplements (Grade A).
Statement 4a
PATIENT BLOOD MANAGEMENT
Three pillars of Patient Blood Management
• In patients undergoing total hip or knee arthroplasty and hip fracture
surgery, preoperative anaemia was highly prevalent, ranging from 24 +/9% to 44 +/- 9%, respectively.
• Postoperative anaemia was even more prevalent (51% and 87 +/- 10%,
respectively).
• Perioperative anaemia was associated with a blood transfusion rate of 45
+/- 25% and 44 +/- 15%, postoperative infections, poorer physical
functioning and recovery, and increased length of hospital stay and
mortality.
• Treatment of preoperative anemia with iron, with or without
erythropoietin, and perioperative cell salvage decreased the need for
blood transfusion and may contribute to improved patient outcomes.
• High-impact prospective studies are necessary to confirm these findings
and establish firm clinical guidelines.
Spahn DR. Anaesthesiology 2010;113:482-95
• 31 of 75 women with iron deficiency treated with IV iron preoperatively.
• IV iron sucrose (760± 290 mg) increased preoperative Hb (Δ Hb: 2.2 ±
1.2 g/dL;P<0.001) and reduced postoperative transfusion rates compared
with the control group (32% vs 0%, respectively; P <0.001).
• Fewer women from the IV iron group were anemic on postoperative day
21 (23% vs 68%; P <0.01).
• No life-threatening adverse events occurred with iron sucrose.
• Because of the rapid increase in Hb levels, IV iron sucrose administration
seems to be an effective approach for treating preoperative anemia and
reducing transfusion rates in this female population.
Diez-Lobo AI et al. TATM. 2007;9:114-119
US Veterans Database (NSQIP)
(n=227,425)
Anaemia
(n=69,229; 30.4%)
30day mortality
30day composite morbidities (9 defined areas)
Multivariate regression
(9 defined subgroups)
(56 cofactors)
Effect of Anaemia on Outcome
• 941,406 patients
• 173 Hospitals
• 2005-2009
• 48,291 transfused
Management of Anaemia
• Restrictive Hb 70-90g/l
• Liberal Hb 90-110g/l
Outcome - BT
Outcome - Mortality
Cost of anaemia on outcome
•
Increased length of hospital stay (median 9 v 6 days, p=0.001)
•
Increased post operative complications (25-35%)
Conclusions
• Avoid anaemia
• Avoid transfusion
THINK IRON EARLY
Assess for Eligibility :
Patients undergoing elective major surgery
Anaemia (Hb: <12 g/dl)
14 - 42 days before operation
Informed consent
Exclusion:
Iron therapy or blood transfusion in 90 days
B12 or Folate deficiency
Unstable cardiac disease
Renal dialysis or creatinine > 180
ALT or AST > 3 x upper limit of normal
Randomisation
1:1 (n=500 planned)
Ferric Carboxymaltose (n= 250)
Dose by weight (1000mg max)
Placebo (n=250)
N/Saline infusion 100
Lost to Follow up / Discontinued (n=15)
Lost to Follow up / Discontinued (n=15)
Analyse (n=235)
Analyse (n=235)
ONCOLOGY
®
Venofer
IV Iron Sucrose
Syner-Med (PP) Ltd
Shander A et al. Transfusion 2010;50:719-732
Dangsuwan P, Manchana T. Gynecol Oncol. 2010;116:522-5
‘The
original question raised in this study of which patients
need iron in addition to ESAs might rather read which patients
need ESAs in addition to iron.’
Steinmetz HT et al. Support Care Cancer. 2010;19:261-9
CONGESTIVE HEART FAILURE
Prevalence of anaemia in CHF
1. Cleland JG et al. Eur Heart J 2003;24:442−463
2. Komajda M et al. Eur Heart J 2003;24:464−474
3. Adams KF et al. Am Heart J 2005;149:209−216
4. Maggioni AP et al. J Card Fail 2005;11:91−98
5. Horwich TB et al. J Am Coll Cardiol 2002;39:1780−1786
6. Silverberg DS et al. J Am Coll Cardiol 2000;35:1737–1744
7. McClellan W et al. Curr Med Res Opin 2004;20:1501–1510
8. van Tellingen A et al. Neth J Med 2001;59:270−279
9. Ezekowitz JA et al. Circulation 2003;107:223-225
10. Cohn JN et al. N Engl J Med 2001;345:1667–1675
11. Anand I et al. Circulation 2005;112:1121–1127
12. Sharma R et al. Eur Heart J 2004;25:1021–1028
13. Anand I et al. Circulation 2004;110:149–154
14. Komajda M et al. Eur Heart J 2006;27:1440–1446
15. O’Meara et al Circulation 2006;113:986−994
Anaemia in HF adversely affects
outcome
• Meta-analysis, 34 studies, n=153,180 HF patients; anemics – 37%1
• Mortality: anemics – 46.8% vs non-anemics – 29.5%; OR=1.96 (1.74−2.21)1
• Anemia independent risk of mortality; adjusted HR – 1.46 (1.26−1.69)1
150
400
Mortality
Anemics
Non-anemics
100
50
CV Non-CV
Reduced LVEF
CV Non-CV
Preserved LVEF
Per 1000 pt-years
Per 1000 pt-years
CHARM program2
Hospital admission
300
200
100
CV Non-CV
CV Non-CV
Reduced LVEF Preserved LVEF
1. Groenveld HF et al. J Am Coll Cardiol 2008;52:818−827; 2. O’Meara E et al. Circulation 2006;113:986−994
Persistence of anaemia in ambulatory HF
patients is related to poor outcome
Kaplan-Meier analysis of all-cause mortality according to anemia status1
6 month follow-up (n=1393)
Total baseline population (n=6159)
100
80
Survival (%)
100
Survival (%)
•
18.6%
60
40
With anemia (n=1058)
Without anemia (n=5101)
20
0
1
2
60
No anemia (n=860)
Resolved anemia (n=143)
Incident anemia (n=210)
Persistent anemia (n=180)
40
20
Log-rank p<0.0001
Chi square= 227
0
80
3
Years
4
5
0
Log-rank p<0.0001
Chi square= 81.2
0
1
2
3
4
5
Years
1. Tang WH et al. J Am Coll Cardiol 2008;51:569–576
Anker SD et al. Eur J Heart Failure 2009;11:1084-1091
Anker SD et al. Eur J Heart Failure 2009;11:1084-1091
Anker SD et al. Eur J Heart Failure 2009;11:1084-1091
Anaemia and cardiovascular disease
Anaemia
CHF
Tissue hypoxia
LVH and eventual
cell death
Peripheral vasodilation
 Ventricular
diameter
 Blood pressure
 Plasma volume
 Sympathetic activity
 Renal blood flow
Fluid retention
 Renin angiotensin
aldosterone ADH
CONCLUSIONS
New concepts in diagnosis and
management of iron deficiency
•
•
•
•
•
Role of hepcidin
True versus functional iron deficiency
Importance of anaemia on clinical outcomes
Risks of transfusion
Role of intravenous iron
THANK YOU