1. 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

2. Outline Iron metabolism Treatment options
Clinical use of intravenous iron-current and developing areas

3. 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)
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

4. Iron content of a balanced diet
A balanced diet contains 5-6 mg of iron/1,000 kcal
Recommended amount of iron – Adult man: mg / day – Adult woman: mg / day

5. 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 iron-bioavailability % 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

6. 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
Men (15-59 years)
4.3
30.0
Seniors
12.0
45.2
1. World Health Organisation Iron Deficiency: Assessment, Prevention and Control.

7. 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

8. Non-haematological benefits of iron1
Physical performance
Thermoregulation
Cognitive function
Restless legs syndrome
Immune function
1. Agarwal R. Am J Neph 2007;27:

10. Iron status without inflammation1
Stage 1
Stage 2
Normal
Iron deficiency
Iron deficiency anaemia
Storage iron
Transport iron
Erythron iron
Ferritin (µg/l)
100±60
< 25
< 10
Transferrin saturation (%)
35±15
< 30
Haemoglobin (g/dl)
Normal (12-13)
Low (< 12-13)
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

11. Iron status with inflammation1
Normal
Iron depletion
Absolute
iron deficiency
Functional iron
deficiency
Storage iron
Transport iron
Erythron iron
Ferritin (µg/l)
100±60
< 25
< 10
>100
Transferrin saturation (%)
35±15
< 30
<20
Haemoglobin (g/dl)
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

12. 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

14. Absolute & functional iron deficiency
Absolute iron
deficiency
Depleted body iron stores
Low serum ferritin (<100ng/ml) or
TSAT <20%
Low hepcidin
Functional iron
deficiency
Inadequate iron supply to meet 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

15. Iron replacement strategies
Dietary iron
Oral iron
Parenteral iron
Blood transfusion

16. 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

17. 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 during ESA therapy
Accelerated erythropoiesis can increase demand for iron beyond the amount supplied orally
Gastrointestinal adverse events
Can affect over 50% of patients
Can adversely affect nutritional intake
Improved if iron tablets are taken with food, but this decreases absorption
Compliance
Pill burden: usually 2 or 3 tablets per day
Affected by gastrointestinal intolerance
Oxidative stress
High oral iron doses can saturate the iron transport system if the iron is rapidly released, resulting in oxidative stress
Macdougall IC. Curr Med Res Opin 2010;26:473–83;
Crichton RR et al. Iron Therapy With a Special Emphasis on Intravenous Administration (4th edition). UNI-MED Verlag AG, Bremen, Germany, 2008

18. 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

19. 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

20. BCSH Guidelines for Clinical Use of Red Cell Transfusions (2001)
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

21. Blood transfusion Cost £122/unit plus admin costs Supply limitations
Risks unique to transfusion

22. 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

23. SHOT Cumulative data: 17 years n=13141
Transfusion reactions which may not be preventable
Possibly or probably preventable by improved practice and monitoring
Adverse events due to mistakes
Copyright SHOT July 2014

24. Summary of treatment options
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
Convenient 2
Fast acting5
Well tolerated2
Malabsorption in inflammatory conditions3
Potential adverse reactions
Potential transfusion reactions6,7
Intolerance3
Invasive
Potential poor compliance3
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
Advantage
Disadvantages
Short lasting effect - Most relevant studies show that approximately 20% of the RBCs is lost in the first 24 hr after transfusion. Even more remarkable is that the average life span is 94 days after a storage period of days - Survival of the fittest?--survival of stored red blood cells after transfusion. Luten M et al 2004
1. Goddard AF et al. Gut 2011;60:1309e1316
2. Gasche C et al Inflamm Bowel Dis 2007;13(12):
3. Macdougall IC. Curr Med Res Opin 2010;26(2):
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):
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:

25. 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)

26. nephrology

27. Renal medicine Erythropoeitin (ESA) licensed in 1989
Intravenous iron improves Hb responses and reduces ESA requirements-overcomes iron“supply” issue
Approved by NICE

28. 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)

29. 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 µg/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
Low
TSAT = transferrin saturation; MCV = mean corpuscular volume; HRC = hypochromic red cells
NICE 2011 Anaemia management in people with chronic kidney disease (CG114)

30. Obstetrics & Gynaecology

31. 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 ©
1. Bodnar LM et al. Am J Epidemiol. 2002;156:903-12

32. Adverse effects of iron deficiency in pregnancy, at delivery and post partum-maternal
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

33. 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)

34. Antenatal iron deficiency anaemia
Very common
Estimated requirements of ~800 mgs extra iron over the course of one pregnancy
Detection poor
Detection late

35. Iron deficiency anaemia becomes more prevalent as pregnancy progresses
Percentage of women
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
First trimester
Second trimester
Third trimester
Scholl TO. Am J Clin Nutr. 2005;81:1218S-1222S

36. 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.

37. Venofer® IV Iron Sucrose
Syner-Med (PP) Ltd

38. 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

39. 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:

40. Oral iron vs IV iron in the postpartum
Bhandal N, Russell R. BJOG 2006;113:

41. The King’s Lynn experience Midwife-led service for prevention/management of anaemia in pregnancy and reduction of transfusion exposure

42. 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

43. Data from King’s Lynn

44. Units used vs number of women transfused

45. 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

46. 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

47. 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
MCV above 99
MCV 81-99
Flow Chart 1a – Anaemia at Booking
See Flow Chart 1b
See Flow Chart 1c
See Flow Chart 1d

48. 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
Dietary advice and Oral Iron
Check Ferritin
(if not previously done)
Ferritin below 30
Ferritin above 30
Unable to tolerate oral iron or failure to show rise in Hb after 2 weeks oral iron
Consider intravenous iron in second trimester
Re-check Hb in 4 weeks after IV Iron
No response
Seek Haematology Advice
Check Haemoglobinopathy Screen
No action
Thalassemia Trait
Normal
Low
Flow Chart 1b – Anaemia at Booking and MCV less than 81
Re-check Hb in 2 weeks

49. 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.

50. Iron Therapy Timeline in O&G

51. Flow Chart 1c – Anaemia at Booking and MCV 81 – 99
Dietary advice and Oral Iron
Check B12/Folate
Ferritin below 30
Normal
Ferritin
Unable to tolerate oral iron or failure to show rise in Hb after 2 weeks oral iron
Consider intravenous iron in second trimester
Low
B12
Re-check Hb in 4 weeks after IV Iron
No response
Seek Haematology advice
Reschedule FBC in
2 weeks
Hb less than 11
(or less than 10.5 if above 12 weeks gestation)
seek Haematology advice
Check Haemoglobinopathy Screen
If low see flow chart 1d
Thalassemia Trait
Check Ferritin
Below 30
Check Hb in 2 weeks
(if not previously done)
Low Folate
Follow flow chart 1d
Flow Chart 1c – Anaemia at Booking and MCV 81 – 99
Hb less than 11g/dl at booking (or less than 10.5 if above 12 weeks gestation) and MCV 81 – 99 = ANAEMIA
AND
MCV 81-99fl

52. Flow Chart 1d – Anaemia at Booking and MCV above 99
Hb less than 11 g/dl at booking (or less than 10.5 if above 12 weeks gestation) and MCV above 99 = ANAEMIA
AND
MCV above 99fl
Check B12/Folate
Low B12
Take sample for intrinsic factor antibodies. Take sample before giving B12 (but do not wait for result)
If antibodies positive = Pernicious Anaemia
Refer to GP
Re-check Hb in 4 weeks
No response
Seek
Haematology Advice
Low Folate
Dietary advice and oral folic acid (5mg daily)
Hydroxycobalamin 1mg x 6 doses im
If antibodies negative
B INDETERMINATE
Hydroxycobalamin 1mg one dose im if still
Request GP re-check B12 3 months post partum
Repeat in 4-8 weeks
B12 <211 = DEFICIENT
High risk if: Vegan Diet, Ileal Disease, Malabsorption, Bariatric Surgery or Family History PA;
Normal
Reschedule FBC in 2 weeks
Hb less than
11, seek Haematology advice
B12 normal
Flow Chart 1d – Anaemia at Booking and MCV above 99

53. Another chance at 28 weeks
Review blood results and ACT ON THEM

54. Flow Chart 2: Anaemia in Pregnancy at 28 weeks
Hb less than 10.5 g/dl at 28 weeks = ANAEMIA
MCV <81 [exclude thalassemia - check booking bloods]
Dietary advice and Oral Iron
MCV above 99
Check B12/Folate
MCV 81-99
Check Ferritin
Low Ferritin (below 30)
Normal Ferritin
Unable to tolerate oral iron or
>34 /40 gestation or Hb <7
Follow IV
Iron protocol
(Confirm iron deficiency – check Ferritin)
Low B12
Take sample for intrinsic factor antibodies. Take sample before giving B12 but do not wait for result
If antibodies positive =
Pernicious Anaemia
Refer to GP
Re-check Hb in 2 weeks
No response
Seek Haematology advice
Low Folate
Dietary advice and oral folic acid
(5mg daily)
B12 <211 = DEFICIENT
High risk if: Vegan Diet, Ileal Disease, Malabsorption, Bariatric Surgery or Family History PA;
Hydroxycobalamin 1mg x 6 doses im
If antibodies negative
B INDETERMINATE
Hydroxycobalami n 1mg one dose im if still
Request GP re-check B12 3 months post partum
Repeat in 2-4 weeks
Recheck Hb in 2 weeks
Continue Oral Iron
Rise in Hb
No rise in Hb
B12 normal
Seek Haematology advice if Hb<10.5
Flow Chart 2: Anaemia in Pregnancy at 28 weeks

55. Iron Therapy Timeline in O&G

56. 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

57. Gastroenterology

58. British Society of Gastroenterology
Guidelines for the management of iron deficiency anaemia 2011
Definition of anaemia
Iron deficiency*
Treatment
Acknowledge WHO cut-offs:
Men Hb <13g/dl
Women Hb <12g/dl
Suggest cut-off for diagnosis of anaemia should be the lower limit of the normal range as defined by laboratory doing thr test.
Low ferritin (cut-off varies between µg/l in absence of inflammation).
Low TSAT.
Low iron.
Raised TIBC.
Raised red cell zinc protoporphyrin.
Raised serum transferrin receptor.
Reticulocyte Hb content or % hypochromic red cells for diagnosis & monitoring of functional ID.
All patients should have iron supplementation to correct anaemia & replenish body stores.
Trial of oral or parenteral iron can help distinguish true iron deficiency.
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

60. Guidelines on the Diagnosis and Management of Iron Deficiency and Anaemia in IBD (Gasche et al, 2007)

61. 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

62. Patient blood management

63. Three pillars of Patient Blood Management

64. 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

65. No life-threatening adverse events occurred with iron sucrose.
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:

66. 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)

67. Effect of Anaemia on Outcome

68. 941,406 patients
173 Hospitals
48,291 transfused

69. Management of Anaemia

71. Restrictive Hb 70-90g/l
Liberal Hb g/l

72. Outcome - BT

73. Outcome - Mortality

74. Cost of anaemia on outcome
Increased length of hospital stay (median 9 v 6 days, p=0.001)
Increased post operative complications (25-35%)

75. Conclusions
Avoid anaemia
Avoid transfusion
THINK IRON EARLY

76. Lost to Follow up / Discontinued (n=15)
Analyse (n=235)
Assess for Eligibility :
Patients undergoing elective major surgery
Anaemia (Hb: <12 g/dl)
days before operation
Informed consent
Randomisation
1:1 (n=500 planned)
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
Ferric Carboxymaltose (n= 250)
Dose by weight (1000mg max)
Placebo (n=250)
N/Saline infusion 100

77. oncology

78. Venofer® IV Iron Sucrose
Syner-Med (PP) Ltd
Shander A et al. Transfusion 2010;50:

80. Dangsuwan P, Manchana T. Gynecol Oncol. 2010;116:522-5

81. ‘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

82. Congestive heart failure

83. Prevalence of anaemia in CHF1 2 3 4 5 6 7 8 9
10,11 12 13 14 14 15
Clinicians frequently identify anemia in their older patients, but U.S. national data on the
prevalence and causes of anemia in this population have not been available. Data are
from the non-institutionalized U.S. population assessed in the third National Health and
Nutrition Examination Survey ( ). Anemia was defined by World Health
Organization criteria; causes of anemia included iron, folate and B12 deficiencies, renal
insufficiency, anemia of chronic inflammation (ACI), formerly termed anemia of chronic
disease, and unexplained anemia (UA). ACI by definition required normal iron stores
with low circulating iron (< 60 μg/dl). After age 50, anemia prevalence rates rose
rapidly, to a prevalence above 20% at age 85 and older. Overall, 11.0% of men and
10.2% of women age 65 and older were anemic. Evidence of nutrient deficiency was
present in one-third of older persons with anemia, ACI and/or chronic renal disease in
one-third, and UA in the remaining one-third. Most anemia was mild; 2.8% of women
and 1.6% of men had hemoglobin < 11g/dl. Therefore, anemia is common, albeit not
severe, in the older population, and a substantial proportion of anemia is of indeterminate
cause. The impact of anemia on quality of life, recovery from illness, and functional
abilities needs to be further investigated in older persons.
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:
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 83

84. 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
100
200
400
Per 1000 pt-years CV
Non-CV
Reduced LVEF
Preserved LVEF
300
Hospital admission 50
150
Mortality
Anemics
Non-anemics
CHARM program2
1. Groenveld HF et al. J Am Coll Cardiol 2008;52:818−827; 2. O’Meara E et al. Circulation 2006;113:986−994 84

85. Total baseline population (n=6159)
Persistence of anaemia in ambulatory HF patients is related to poor outcome
Kaplan-Meier analysis of all-cause mortality according to anemia status1 20 40 60 80
100
18.6% 1 2 3 4 5
Log-rank p<0.0001
Chi square= 227
Total baseline population (n=6159)
Survival (%)
Years
Without anemia (n=5101)
With anemia (n=1058)
Chi square= 81.2
6 month follow-up (n=1393)
Resolved anemia (n=143)
No anemia (n=860)
Incident anemia (n=210)
Persistent anemia (n=180)
1. Tang WH et al. J Am Coll Cardiol 2008;51:569–576

86. Anker SD et al. Eur J Heart Failure 2009;11:1084-1091

87. Anker SD et al. Eur J Heart Failure 2009;11:1084-1091

88. Anker SD et al. Eur J Heart Failure 2009;11:1084-1091

89. Cardiorenal anaemia syndrome: a vicious circle of destruction
CHF
CRF
Anaemia

90. Anaemia and cardiovascular disease
CHF
Tissue hypoxia
LVH and eventual cell death
Peripheral vasodilation
 Ventricular diameter
 Blood pressure
 Plasma volume
 Sympathetic activity
Fluid retention
 Renal blood flow
 Renin angiotensin aldosterone ADH

91. CONCLUSIONS

92. 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

93. THANK YOU